Porphyrin Science by Women

Photodynamic methods have found application not only in the treatment process as photodynamic therapy but also for the early detection of neoplastic lesions and tumors as photodynamic diagnosis. Early detection of the disease allows not only to avoid the patient’s lifetime risk but also significantly reduce the costs of anticancer therapy, which are increasing every year. There is a constant search for new and more effective photosensitizers which will provide safety in therapy while maintaining efficiency. This paper summarizes recent reports focused on the photodynamic diagnosis of oral cancers. Moreover, it shows methods of the photodynamic treatment of oral verrucous hyperplasia, erythroleukoplakia, and oral leukoplakia. The treatment of choice for these diseases is a surgical excision, which always leads to scar formation. Photodynamic therapy provides a new scar-less tool for the treatment.

The cationic porphyrin meso-tetra(4-N-methylpyridyl)porphine (TMPyP) has a high yield of singlet oxygen generation upon light activation and a strong affinity for DNA. These advantageous properties have turned it into a promising photosensitizer for use in photodynamic therapy (PDT). In this review, we have summarized the current state-of-the-art applications of TMPyP for the treatment of cancer as well as its implementation in antimicrobial PDT. The most relevant studies reporting its pharmacokinetics, subcellular localization, mechanism of action, tissue biodistribution and dosimetry are discussed. Combination strategies using TMPyP-PDT together with other photosensitizers and chemotherapeutic agents to achieve synergistic anti-tumor effects and reduce resistance to therapy are also explored. Finally, we have addressed emerging applications of this porphyrin, including nanoparticle-mediated delivery, controlled drug release, biosensing and G-quadruplex stabilization for tumor growth inhibition. Altogether, this work highlights the great potential and versatility that TMPyP can offer in different fields of biomedicine such us cancer treatment or antimicrobial therapy.

Photodynamic therapy has become of interest in many European countries. Since, most of national authorities and all medical journals require the registration of the clinical study on the database in order to be published, information regarding clinical studies are now available. This article aims to synthetize data gathered thanks to this database. The keywords used for this analysis was: (i) status: “All studies “(recruiting, completed, terminated, we did not take into account unknown status), (ii) condition or disease: “Photodynamic Therapy”, (iii) country: name of each European country. Since 2003, 76 clinical trials were registered in Europe. Most clinical studies are performed in Germany (22), France (20) and UK (19). These 3 countries represent 80% of all studies performed in Europe. However 21 European countries have one or more studies on PDT. Clinical studies were mainly performed on skin. Actinic Keratosis treatment (20 studies) represents more than 45% of all studies. 21% were focused on eye, mainly on Age Macular Degeneration (AMD) (8 studies). In 2018, ten (10) clinical trials are in the recruitment phase. On November, 10, 2017, Padeliporfin (STEBA Biotech S.A, Luxembourg) obtained the marketing authorization throughout the European Union. Despite the critical importance of trial registration, compliance with requirements from governmental regulators which mandate the prospective registration of clinical trials has been imperfect. Besides, a large proportion of registry entries are never updated to reflect study completion. However, this review clearly demonstrated that PDT is progressively used in most European countries.

This minireview describes the complexity of the molecular mechanisms involved in the tumor response to photodynamic treatment (PDT). Different aspects of reactive oxygen (ROS) and nitrogen species (RNS) induced by PDT will be examined. In particular, we will discuss the effect of ROS and RNS on cell compartments and the main mechanisms of cell death induced by the treatment. Moreover, we will also examine host defense mechanisms as well as resistance to PDT.

Porphyrin-based molecules are actively studied as dual function theranostics: fluorescence-based imaging for diagnostics and fluorescence-guided therapeutic treatment of cancers. The intrinsic fluorescent and photodynamic properties of the bimodal molecules allows for these theranostic approaches. Several porphyrinoids bearing both hydrophilic and/or hydrophobic units at their periphery have been developed for the aforementioned applications, but better tumor selectivity and high efficacy to destroy tumor cells is always a key setback for their use. Another issue related to their effective clinical use is that, most of these chromophores form aggregates under physiological conditions. Nanomaterials that are known to possess incredible properties that cannot be achieved from their bulk systems can serve as carriers for these chromophores. Porphyrinoids, when conjugated with nanomaterials, can be enabled to perform as multifunctional nanomedicine devices. The integrated properties of these porphyrinoid-nanomaterial conjugated systems make them useful for selective drug delivery, theranostic capabilities, and multimodal bioimaging. This review highlights the use of porphyrins, chlorins, bacteriochlorins, phthalocyanines and naphthalocyanines as well as their multifunctional nanodevices in various biomedical theranostic platforms.

In this review we present an updated survey of the main synthesis methods of gold nanoparticles (AuNPs) in order to obtain various tailored nanosystems for biomedical imaging. The synthesis approach significantly impacts on the AuNPs properties such as surface chemistry, biocompatibility and cytotoxicity. In recent years, nanomedicine emphasized the development of functionalized AuNPs for biomedical imaging. AuNPs are a good option for used as delivery photosensitizer agents for PDT of cancer. For example, the complex formed from AuNPs functionalized with PEGylate porphyrins presents several advantages in the medical field such as a better use in photodynamic therapy because of high triplet states and singlet oxygen quantum yield efficiency of porphyrin molecules.

Fluorescence and SPECT/PET imaging are powerful tools currently in use by the scientific community and receiving a great attention for the development of dual-modality imaging agents. BODIPYs are among the most promising candidates to be used for such functions due their excellent absorbance and fluorescence properties as well as their ease of radiolabeling without compromising their biological properties. In this manuscript we present an overview of BODIPY radiolabeling methods and their relevance to the development of multimodality agents.

Since their discovery in 1968, the BODIPYs dyes (4,4-difluoro-4-bora-3a, 4a diaza-s-indacene) have found an exponentially increasing number of applications in a large variety of scientific fields. In particular, studies reporting bioapplications of BODIPYs have increased dramatically. However, most of the time, only in vitro investigations have been reported. The in vivo potential of BODIPYs and aza-BODIPYs is more recent, but considering the number of in vivo studies with BODIPY and aza-BODIPY which have been reported in the last five years, we can now affirm that this family of fluorophores can be considered important as cyanine dyes for future in vivo and even clinical applications. This review aims to present representative examples of recent in vivo applications of BODIPYs or aza-BODIPYs, and to highlight the potential of these dyes for optical molecular imaging.

N-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules (e.g. ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

Human gliomas are one of the most prevalent and challenging-to-treat adult brain tumors, and thus result in high morbidity and mortality rates worldwide. Current research and treatments of gliomas include surgery associated with conventional chemotherapy, use of biologicals, radiotherapy, and medical device applications. The selected treatment options are often guided by the category and aggressiveness of this deadly disease and the patient’s conditions. However, the effectiveness of these approaches is still limited due to poor drug efficacy (including delivery to desired sites), undesirable side effects, and high costs associated with therapies. In addition, the degree of leakiness of the blood–brain barrier (BBB) that regulates trafficking of molecules in and out of the brain also modulates accumulation of adequate drug levels to tumor sites. Active research is being pursued to overcome these limitations to obtain a superior therapeutic index and enhanced patient survival. One area of development in this direction focuses on the localized application of photodynamic therapy (PDT) drugs to cure brain cancers. PDT molecules potentially utilize multiple pathways based on their ability to generate reactive oxygen species (ROS) upon photoactivation by a suitable light source. In this communication, we have attempted to provide a brief overview of PDT and cancer, photoactivation pathways, mechanism of tumor destruction, effect of PDT on tumor cell viability, immune activation, various research attempted by applying PDT in combination with novel strategies to treat glioma, role of BBB and clinical status of PDT therapy for glioma treatment.

The therapeutic value of vascular targeted photodynamic therapy (VTP) for cancer has already been recognized in the clinic: TOOKAD^® has been clinically approved in Europe and Israel for treatment of men with low-risk prostate cancer. When light is applied shortly after intravenous administration of the photosensitizer, the damage is primarily done to the vasculature. This results in vessel constriction, blood flow stasis, and thrombus formation. Subsequently, the tumor is killed due to oxygen and nutrient deprivation. To further increase treatment specificity and to reduce undesired side effects such as damaging to the surrounding healthy tissues, efforts have been made to selectively target the PS to the tumor vasculature, an approach named molecular targeted VTP (molVTP). Several receptors have already been explored for this approach, namely CD13, CD276, Extra domains of fibronectin (A, B), Integrin αvβ3, Neuropilin-1, Nucleolin, PDGFRβ, tissue factor, and VEGFR-2, which are overexpressed on tumor vasculature. Preclinical studies have shown promising results, further encouraging the investigation and future application of molVTP, to improve selectivity and efficacy of cancer treatment. This strategy will hopefully lead to even more selective treatments for many cancer patients.

Porphyrins and phthalocyanines are photosensitizers (PS) that are used in clinical imaging, detection of cancer cells and are particularly applied in photodynamic therapy (PDT). Many scientists have been focused on the design of different porphyrin compounds. However, similar to other anti-cancer agents, they cannot selectively recognize tumor tissues. Scientists are seeking new methods to overcome this problem and to find appropriate targeted delivery strategies. Plant lectins are especially suitable molecules for such targeting as they preferentially recognize specific antigens on the glycosylated cancer cells. This review will give more detailed information about the dual function of lectins and their interactions with PSs, which is a new perspective in targeted PDT. The implications and potential applications of such studies will also be discussed.

We have developed Mn porphyrins (MnPs) initially as mimics of superoxide dismutase (SOD) enzymes based on structure–activity relationships. Several cationic Mn porphyrins, being substituted with cationic ortho N-alkyl- or alkoxyalkylpyridyl groups in meso positions of the porphyrin ring, have been identified as potential therapeutics based on their high SOD-like activity and high bioavailability. Two of those [Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP⁵⁺ (BMX-010, AEOL10113) and Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, MnTnBuOE-2-PyP⁵⁺ (BMX-001)] are now in five Phase II clinical trials. Studies of ours, and those of others, contributed to the understanding of the diverse activities of these compounds. With biologically compatible potentials and four biologically accessible oxidation states, Mn porphyrins interact with numerous reactive species, both as oxidants and reductants. Among those reactions, their abilities to (catalytically) oxidize S-glutathionylate protein thiols may perhaps be their major in vivo mode of action. Via S-glutathionylation, MnPs modulate actions of signaling proteins and, in turn, cellular apoptotic and proliferative pathways. During the major part of our stay in the USA, our lives have been dedicated to Mn porphyrins. Our families and especially our son and his three babies have been our inspiration not to give up on a life often burdened with hardship. It is thus our immense pleasure to see our compounds in clinical trials. Above all, we hope that our story will inspire future researchers to persevere — women in particular.

Novel chloroindium(III) complexes of tetra(4-methylthiophenyl)porphyrin (2a) and tetra-2-thienylporphyrin (2b) dyes have been synthesized and characterized. The main goal of the project was to identify fully symmetric porphyrin dyes with Q-band regions that lie partially in the therapeutic window that are suitable for use in photodynamic therapy (PDT). 2a and 2b were found to have fluorescence quantum yield values ≤ 0.01 and moderately high singlet oxygen quantum yields (0.54–0.73) due to heavy atom effects associated with the sulfur and indium atoms. The dark toxicity and PDT activity against epithelial breast cancer cells (MCF-7) were investigated over a dose range of 3.0–40 μg·mL⁻¹. The in vitro dark cytotoxicity of 2a is significantly lower than that of 2b at ≤ 40 μg·mL⁻¹. 2a was conjugated with gold nanoparticles (AuNPs) to form a nanoconjugate (2a-AuNPs), which exhibited a higher singlet oxygen quantum yield (Φ_Δ) value and PDT activity than was observed for 2a alone. The results suggest that the AuNPs nanoconjugates of readily synthesized fully symmetric porphyrin dyes are potentially suitable for PDT applications, if meso-aryl substituents that provide scope for nanoparticle conjugation can be introduced that shift the Q bands into the therapeutic window.

In this study we evaluated the impact of iodine substitution on the ability of subphthalocyanines (SubPc) to stimulate or regulate the function of macrophages. Previous studies have focused on the usage of phthalocyanines and their derivatives as treatment options against different types of cancer. In order to obtain better prognosis rates, their possible effects on the immune system cells should be delineated. Unique subphthalocyanines were designed and synthesized by our group and a derivative was generated via iodine substitution. In our study we further tested the effects of the new Subpcs on macrophage cell lines. Macrophages play an important role in the immune system through cytokine production and antigen presentation to other types of the immune system cells. They can define the type and the strength of the immune responses against a particular danger signal. Based on pro-inflammatory cytokine (TNFα, IL1β and IL6) production levels by macrophages, unsubstituted SubPc had anti-inflammatory properties. However, iodine substitution on the same SubPc created a completely opposite effect since these iodo-substituted SubPc exerted an immunostimulatory effect on macrophages based on significant increases in the pro-inflammatory cytokine production levels compared to the untreated controls. While SubPcs can be used to suppress the pro-inflammatory activities of the macrophages, iodine-substituted SubPcs have potentials to be used as adjuvants and immunostimulatory molecules.

This study presents a novel phthalonitrile derivative (2) bearing (trifluoromethoxy) phenoxy groups in 4,5 positions. Cyclotetramerization of (2) in N,N-dimethylaminoethanol (DMAE) gave a series of peripherally octa-substituted metallophthalocyanines (3-Zn, 3-Co and 3-Cu). The newly synthesized phthalocyanines have been characterized by a combination of various spectroscopic techniques. Effects of solvent nature on aggregation behavior of 3-Zn were studied using different solvents such as acetone, CHCl₃ and dichloromethane (DCM). In addition, the aggregation behavior of the phthalocyanine complex 3-Zn was examined in DCM at different concentrations ranging from 4 × 10^-6−14 × 10^-6 M. Antimicrobial activities of synthesized compounds were tested by using the thin layer chromotography (TLC)-direct bioautography and disk diffusion methods. In both assays, the molecules showed activity on the tested Gram (+) bacteria. Antioxidant activities of the molecules, on the other hand, were determined by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and a reducing power assay. The highest activity was obtained with 3-ZnPc for both methods.

An isothiocyanato-functionalized phthalocyanine (Pc) was synthesized in good yield from the corresponding amine-substituted Pc. This Pc reacted with ethanolamine, biotin hydrazine, and biotin diethylamine under mild conditions (room temperature in DMF or DMSO in the presence of TEA) to produce the corresponding thiourea products in 60–75% yields. All Pcs showed intense Q absorptions in DMF around 677 nm, emissions centered at 683 nm, and fluorescence quantum yields in the range 0.18–0.27. The Pcs were phototoxic to human carcinoma HEp2 cells (IC₅₀ ~ 7 at 1.5 J/cm²) and localized in multiple organelles, including the lysosomes, Golgi and ER. One biotin-Pc conjugate was injected via tail vein into nude mice bearing HT-29 tumors and demonstrated selective localization in the tumor tissue.

Tetraphenylporphyrins (TPPs) have been proposed for the treatment of retinoblastoma by photodynamic therapy. Glycoconjugated compounds were synthesized for improving TPP solubility and amphipathy, and to specifically target mannose receptors overexpressed at the surface of cells. The efficiency of four TPP derivatives with different chemical structures was compared by phototoxicity tests and flow cytometry experiments. Interestingly, the absence/presence and distribution of saccharide moieties in the various compounds affected differently their mechanism of interaction with cancer cells and their phototoxic efficiency. For glycodendrimeric TPP-1 and TPP-2 incubated with retinoblastoma cells, a fast two-step uptake-equilibrium process was observed, whereas for a dendrimeric TPP without saccharide moieties (TPP-1c) and a glycoconjugated compound with no dendrimeric structure (TPP(DegMan)₃) uptake was very slow. The difference in uptake profiles and kinetics between TPP-1c on the one hand and TPP-1 and TPP-2 on the other hand would account for the interaction of the two glycodendrimeric compounds with a mannose receptor. These TPPs encapsulated in endosomes would induce less damage to cells upon illumination. TPP(DegMan)₃ showed the highest phototoxicity, but its efficiency was unaffected by pretreatment of cells by mannan. The penetration of this glycoconjugated compound in cells and its phototoxic effect appeared independent of its interaction with a mannose receptor. Thus, if glycoconjugation influenced TPPs behavior in solution and interaction with serum proteins, phototoxicity was not necessarily related to upfront molecular recognition.

Antibiotic resistance is an increasing healthcare problem worldwide. In the present study, the effects of antimicrobial photodynamic therapy (APDT) of ZnPc and ZnPc-integrated TiO₂ nanoparticles (ZnPc-TiO₂) were investigated against Staphylococcus aureus. A light emitting diode (LED) (630–700 nm, 17.4 mW/cm²) was used on S. aureus at different light doses (8 J/cm² for 11 min, 16 J/cm² for 22 min, 24 J/cm² for 33 min) in the presence of the compounds under the minimum inhibitory concentration values. Both compounds showed similar phototoxicity toward S. aureus when high light doses (16 and 24 J/cm²) were applied. In addition, the success of APDT increased with an increasing light dose.

A series of glycosylated photosensitizers (porphyrin, chlorin, and isobacteriochlorin) in the presence of plasma proteins: bovine serum albumin (BSA) and human serum albumin (HSA), were investigated in a buffer at pH 7.4, using ultraviolet-visible (UV-vis) absorption and fluorescence spectroscopies. Due to the excitation of the tryptophan residue of BSA and HSA, its fluorescence emission was monitored around 340 nm. During each titration experiment and with each addition of the corresponding glycosylated photosensitizer, there was a concentration-dependent quenching of the intrinsic fluorescence of BSA and HSA. Using Stern–Volmer and double logarithmic plots we determined that fluorescence quenching was static for all molecules. We calculated the average binding constant for BSA and HSA for each porphyrin-type compound. To support our experimental studies, computational molecular docking and molecular dynamics simulations were used to identify the binding sites and binding poses of the each of the glycosylated photosensitizers onto BSA and HSA. The three compounds are binding to the Hemin site located in the subdomain IB of BSA forming strong interactions with Trp134, while they are binding to the subdomain IIA of HSA close to the Sudlow’s site I, and interacting with Trp214.

With the increased risk of infectious disease transmissions, photodynamic inactivation of some microorganisms for antimicrobial applications has been extensively studied in recent years. In this article, we describe the synthesis of novel photo-bactericidal materials by grafting propargylated 5,10,15,20-tetra(4-pyridyl)porphyrin on kraft pulp fibers. The grafting was carried out by a Huisgen’s 1,3-dipolar azide-alkyne cycloaddition reaction. This material has been investigated for its antibacterial properties against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. An interesting photo-bactericidal activity was shown: this material can be used to limit the growth of bacteria on surfaces and the formation of biofilms.

The increasing world-wide rate of antibiotic resistance as well as the capacity of microorganisms to form biofilms, have led to a higher incidence of mortal infections that require alternative methods for their control. Antimicrobial photodynamic therapy (aPDT) emerged as an effective solution against resistant strains. The present work aims to evaluate the aPDT efficiency of a photosensitizer (PS) based on a low-cost formulation constituted by five cationic porphyrins (FORM) and its potentiation effect by KI on a broad spectrum of microorganisms under white light (380−700 nm, 25 W/m²). The aPDT assays were performed with different concentrations of FORM (0.1 to 5.0 μM) and 100 mM of KI on planktonic and biofilm forms of gram-positive (methicillin resistant Staphylococcus aureus–MRSA) and gram-negative (Escherichia coli resistant to chloramphenicol and ampicillin) bacteria, of the fungi Candida albicans and on a T4-like bacteriophage as a mammalian virus model. The results indicate that the FORM alone is an efficient PS to photoinactivate not only gram-negative and gram-positive bacteria, but also C. albicans, in planktonic and biofilm forms, and T4-like phage at low concentrations (< 5.0 μM). The presence of KI enhanced the photodynamic effect of this FORM for all microorganisms on the planktonic form, allowing the reduction of PS concentration and treatment time. The results also show that the combination FORM/KI is highly efficient in the elimination of already well-established biofilms of E. coli, S. aureus and C. albicans. This effect is probably associated with longer-lived iodine reactive species produced during the aPDT treatment.

Aminolevulinic acid and hexyl-aminolevulinate serve as biological precursors to produce photosensitive porphyrins in cells via the heme biosynthetic pathway. This pathway is integral to porphyrin-based photodynamic diagnosis and therapy. By adding exogenous hexyl-aminolevulinate to rat bladder cancer cells (AY27, in vitro) and an animal bladder cancer model (in vivo), fluorescent endogenous porphyrin production was stimulated. Lipophilic protoporphyrin IX was identified as the dominant species by reverse high-pressure liquid chromatography. Subcellular porphyrin localization in the AY27 cells was evaluated by confocal laser scanning microscopy and showed almost quantitative bleaching after 20 s. From this study, we ascertained that the protocol described herein is suitable for hexyl-aminolevulinate-mediated photodynamic therapy and diagnosis when protoporphyrin IX is the active agent.

This study, subphthalocyanines (SubPc) and SubPc integrated TiO₂ nanoparticles (SubPc-TiO₂) were synthesized as novel photosensitizers. Their PDT effects were evaluated. Furthermore, nuclear imaging potential of ¹³¹I-labelled SubPc/SubPc-TiO₂ were examined in mouse mammary carcinoma (EMT6) and cervix adenocarcinoma (HeLa) cell lines. The uptake results show that SubPc labelled with ¹³¹I radionuclide (¹³¹I-SubPc) in EMT6 and HeLa cell lines was found to be approximately the same as in the WI38 cell line. However, the uptake values of SubPc-TiO₂ labelled with ¹³¹I (¹³¹I-SubPc-TiO₂) in EMT6 and HeLa cell lines were determined to be two times higher than in the WI38 cell line. In other words, the target/non-target tissue ratio was identified as two in the EMT6 and HeLa cell lines. ¹³¹I-SubPc-TiO₂ is promising for imaging or treatment of breast and cervix tumors. In vitro photodynamic therapy studies have shown that SubPc and SubPc-TiO₂ are suitable agents for PDT. In addition, SubPc-TiO₂ has higher phototoxicity than SubPc. As a future study, in vivo experiments will be held and performed in tumor-bearing nude mice.

Novel peripherally and non-peripherally 3-methylindole-substituted zinc phthalocyanine derivatives were synthesized as photosensitizers for photodynamic therapy in cancer treatment. The photophysical, photochemical and photobiological properties of targeted phthalocyanines were also investigated. For this purpose, the fluorescence and singlet oxygen quantum yields, and fluorescence lifetime values of the final compounds were determined in DMF solutions. The phototoxicity and cytotoxicity of the phthalocyanine complexes were tested against the invasive human breast cancer cell line (MDA-MB-231) for determination of their photosensitizing ability in the area of photodynamic therapy. It was revealed that while peripherally 3-methylindole-substituted phthalocyanine was found to be toxic for cells in both dark and light conditions, its non-peripherally substituted phthalocyanine analogue significantly caused cell death following light irradiation. A preliminary assay suggested that the non-peripherally linked phthalocyanine could be a suitable candidate for cancer treatment via photodynamic therapy techniques.

Porphyrin derivatives are highly attractive in the construction of multifunctional molecular platforms with interesting properties and applications. In this regard, we report here the use of a multifunctional porphyrin-based molecular platform as a photosensitizer for photodynamic therapy and as a drug carrier. This molecular platform was constructed by conjugating a host molecule, cucurbit[7]uril to a triglycosylated tetraphenyl porphyrin and serves very efficiently as a photosensitizer in the inactivation of both gram-negative (Escherichia coli, E. coli) and gram-positive bacteria (Bacillus subtilis, B. subtilis) and growth inhibition of cancer cells as well as a doxorubicin (DOX) carrier for chemo-photodynamic dual cancer therapy. Another remarkable feature of this photosensitizer is that it shows negligible cytotoxicity in the dark.

Porphyrin-peptide conjugates have a breadth of potential applications, including use in photodynamic therapy, boron neutron capture therapy, as fluorescence imaging tags for tracking subcellular localization, as magnetic resonance imaging (MRI) positive-contrast reagents and as biomimetic catalysts. Here, we have explored three general routes to porphyrin-peptide conjugates using the Cu(I)-catalyzed Huisgen-Medal-Sharpless 1,3-dipolar cycloaddition of peptide-containing azides with a terminal alkyne-containing porphyrin, thereby generating porphyrin-peptide conjugates (PPCs) comprised of a cationic porphyrin coupled to short antimicrobial peptides. In addition to characterizing the PPCs using a variety of spectroscopic (UV-vis, ¹H- and ¹³C-NMR) and mass spectrometric methods, we evaluated their efficacy as photosensitizers for the in vitro photodynamic inactivation of Mycobacterium smegmatis as a model for the pathogen Mycobacterium tuberculosis. Difficulties that needed to be overcome for the efficient synthesis of PPCs were the limited solubility of the quaternized pyridyl porphyrin in common solvents, undesired (de)metallation and transmetallation, and chromatographic purification. Photodynamic inactivation studies of a small library of PPCs against Mycobacterium smegmatis confirmed our hypothesis that the porphyrin-based photosensitizer maintains its ability to efficiently inactivate bacteria when conjugated to a small peptide by upwards of 5–6 log units (99.999+%) using white light illumination (400–700 nm, 60 mW/cm², 30 min). Further, hemolysis assays revealed the lack of toxicity of the PPCs against sheep blood at concentrations employed for in vitro photodynamic inactivation. Taken together, the results demonstrated the ability of PPCs to maintain their antimicrobial photodynamic inactivation efficacy when possessing a short cationic peptides for enabling the potential targeting of pathogens in vivo.

Breast cancer is one of the most common types of cancers prevalent in women. Several types of breast cancers can easily metastasize to bone and cause disease complications such as hypercalcemia and pathologic fracture, thus compromising the quality of life of people affected by it. Bisphosphonate drugs are often used for the treatment of bone metastasis to suppress osteoclastic bone resorption. However, bisphosphonate has adverse effects on the gastrointestinal tract and kidneys and also induces osteonecrosis of the jaw. Photodynamic therapy (PDT) is an alternative cancer treatment approach with minimal invasiveness. It is a combination treatment that uses photosensitizers, which accumulate in tumor cells, followed by laser irradiation. We previously reported that the cellular incorporation of 5-aminolevulinic acid (5-ALA), which was a precursor of protoporphyrin IX (PpIX), was regulated by reactive oxygen species derived from mitochondria (mitROS). In this study, we investigated the incorporation of 5-ALA, accumulation of PpIX, and subsequent effects on cell viability after laser irradiation of two different breast cancer cell lines with different metastaticites. The highly metastatic breast cancer cell line 4T1E/M3 showed a significant increase in ROS production after treatment with indomethacin (IND). In addition, IND treatment enhanced the cellular uptake of 5-ALA via PEPT1 upregulation in 4T1E/M3, but not in the non-metastatic cell line. Overall, metastatic breast cancer is likely to be sensitive to ROS and activate signaling pathways associated with 5-ALA transportation, suggesting that ALA-PDT could be an effective treatment with low invasiveness for metastatic breast cancer.

Novel fluorescent organic nanoparticles made from citric acid and diethylenetriamine were used as biocompatible and highly water-soluble nanocarriers for hydrophobic tetraphenylporphyrin (TPP). The tetraphenylporphyrin units were covalently attached to the nanoparticles, generating conjugated nanoparticles which retain water solubility and preserve the photophysical properties of monomeric TPP. The conjugated nanoparticles show two distinct fluorescence features: blue emission from the nanoparticle when excited in the near-UV (360 nm) and characteristic far-red emission of the TPP when excited in the visible (Soret band or Q bands). The uptake of the conjugated nanoparticles in live human neuroblastoma cancer cells was evidenced using two-photon microscopy. These experiments demonstrate that the fluorescent organic nanoparticles do act as efficient nanocarriers, allowing cell internalization of hydrophobic porphyrins. These conjugated nanoparticles appear as promising nanotools for theranostic (based on the combination of imaging and monitoring of the nanoparticle fluorescence) and therapeutic (photodynamic therapy by selectively exciting the grafted porphyrin units) modalities.

A novel Sn(IV) meso-tetraacenaphthylporphyrin (SnTAcP) has been synthesized and characterized. SnTAcP was complexed with methyl-β-cyclodextrin (mβ-CD), a nanocarrier that enhances water solubility, and the complexes were evaluated as PDT agents using MCF-7 breast cancer cells. A relatively low singlet oxygen quantum yield value of 0.36 was obtained in DMF, and the lowest energy Q band lies at 608 nm on the edge of the therapeutic window. SnTAcP was found to be non-toxic in the dark and phototoxic towards MCF-7 breast cancer cells with a half-maximal inhibitory concentration (IC₅₀) value of 11 ± 1.1 μg·mL⁻¹ after 30 min of irradiation with a 625 nm Thorlabs LED that provides a dose of 432 J·cm⁻². A higher IC₅₀ value of 21 ± 1.1 μg·mL⁻¹ was obtained for the mβ-CD inclusion complex of SnTAcP.

Subcellular organelle-targeted photosensitizers have recently reported to be effective photodynamic therapy (PDT) agents. In this work, three porphyrin-derived photosensitizers, containing one, two or four triphenylphosphonium targeting groups, were synthesized and characterized by NMR, HRMS, UV-vis and fluorescence spectroscopy. These photosensitizers showed similar photophysical properties to classical porphyrins and exhibited excellent ¹O₂ quantum yields in acetonitrile. Subcellular colocalization indicated that all three photosensitizers specifically stain the mitochondria of HeLa cells. Photosensitizer mito-dp, containing two triphenylphosphonium cations was found to be the most uptaken by cells and exhibited the best PDT effect with an effective phototoxicity (IC₅₀ (light) = 12.4 nM), suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.

The administration of photosensitizers and their biocompatibility is crucial to the success of photodynamic therapy treatment. Amongst the various strategies developed to administer photosensitizers of low water-solubility, the use of polyvinylpyrrolidone (PVP), an FDA-approved food additive, is emerging as extremely promising. Its effect on photodynamic outcome was compared to more classical formulation in DMSO and direct solubilization in water. The tetrakis (2-(2-(2-methoxyethoxy) ethoxy)ethoxy)-Zn(II) phthalocyanine chosen as the model photosensitizer for this study proved to be a powerful photosensitizer. Even if slightly less efficient than DMSO formulation, PVP formulation proved to work very well, with submicromolar IC₅₀ and IC₉₀ values against MDA-MB-231 human cancer cells.

The results of recent studies on the optical limiting properties of BODIPY dyes at 532 and 1064 nm are described and compared. The optical limiting properties of novel 1,7-dimethyl-3,5-di-4-dihydroxyborylstyryl- and 3,5,7-tristyryl-1-methyl-BODIPY dyes were studied in CH₂Cl₂ and C₆H₆ and polystyrene thin films using the open aperture Z-scan technique at 532 nm with nanosecond laser pulses to provide an example of how the effective nonlinear absorption coefficient, the third order susceptibility, hyperpolarizability and limiting thresholds can be calculated.

The synthesis and characterization of a novel dibrominated 1,3,5-tristyrylBODIPY dye is reported, and its potential utility as a singlet oxygen photosensitizer and optical limiting material is assessed. The main spectral band lies in the therapeutic window, and there is a moderately high singlet oxygen quantum yield making the dye potentially suitable for use in biomedical applications and as an optical limiting dye at 532 nm. The optical limiting parameters are comparable to those reported previously for 3,5-distyrylBODIPYs, which suggests that mixtures of 3,5-distyryl and 1,3,5-tristyryl compounds that are formed in Knoevenagel condensation reactions could be used for this application. Theoretical calculations are used to assess the effect of 1,3,5-tristyryl substitution. A smaller red shift of the main spectral band is observed upon styrylation at the 1-position than is the case with the 3,5-positions due to there being smaller MO coefficients at this position, limiting the utility of this structural modification method for shifting the main BODIPY spectral band further into the therapeutic window.

A near-infrared absorbing boron-dipyrromethene (BODIPY) chromophore coupled with two benzoquinone moieties at its 3,5-positions, 3, was prepared via Knoevenagel condensation of 1,3,5,7-tetramethyl-8-(4′-benzonitrile) BODIPY 1 with 3,5-di-tert-butyl-4-hydroxybenzaldehyde to afford 1,7-dimethyl-3,5-di-(4′-hydroxy-3′,5′-di-tert-butyl styryl)-8-(4′-benzonitrile) BODIPY 2, followed by oxidization with Ag₂O in good yield (91%). The UV-vis-NIR absorption spectrum of 3 exhibits two major bands at 795 and 895 nm in the near-IR region, while 2 shows maximum absorbance at 661 nm and strong fluorescence at 692 nm (Φ_F = 0.59). The cyclic voltammetry of 3 consists of two pairs of reversible one-electron reductions at -0.61 V and -0.88 V and two pairs of one-electron oxidation waves at 0.26 V and 0.54 V. Compared with the redox potentials of 2 (E_{1/2 red1} = -1.32 V and E_{1/2 ox1} = 0.25 V), the first reduction of 3 is anodically shifted for 710 mV, whereas the first oxidation potential is close. Theoretical calculation reveals that conjugation with the benzoquinone moieties on the BODIPY chromophore significantly lowers the LUMO energy level and the HOMO–LUMO energy gap, resulting in a dramatic bathochromic shift of the S₀–S₁ transition of 3 compared with that of 2. X-ray crystallographic analysis of 3 reveals that the whole molecule adopts a V-type twisted conformation along the delocalized π-conjugated pathway.

This review article briefly describes the available synthetic approaches for mesoarylporphyrins giving particular emphasis for one-pot nitrobenzene and nitrobenzene/NaY methods regarding the synthesis of meso-halogenated arylporphyrins. The review also describes the relevant applications of these halogenated porphyrins and their metalloporphyrin counterparts, prepared via nitrobenzene method, as photosensitizers for therapy (PDT and PDI), diagnostic (molecular contrast agents) and also for catalytic oxidation and CO₂ cycloaddition reactions to epoxides.

Porphyrins are tetrapyrrolic aromatic macrocycles and ubiquitous in nature. They are excellent dyes with strong absorption in the visible region (400–700 nm) and they exhibit decent fluorescence in the red region (620–900 nm). Carbazole is a nitrogen-containing electron rich aromatic heterocycle which can be linked to porphyrins and other chromophores. This review provides an overview of the different synthetic strategies that have been employed to prepare carbazole-substituted porphyrins and carbazole-fused porphyrinoids and similar systems. It also shows that how the substitution of carbazole occurs on the porphyrin core can alter its optical and electronic features. Introduction of carbazole moieties in the porphyrin ring resulted in fused porphyrinoids with changed aromaticity and significantly altered electronic features of the molecules.

To improve conjugation between a central porphyrin core and its peripheral fluorenyl antennae, we have introduced in the meso-tetrafluorenyl porphyrin (TFP-Bu) unit an ethynyl spacer at the meso positions. By this means, we have synthesized and characterized a new meso-alkynyl fluorenyl porphyrin (TAFlP). We discuss the effect of this extra extension of the π manifold on the optical properties. This enlarged porphyrin core, TAFlP, is foreseen as a key building block for the design of new dendrimers for theranostic applications. The constant improvement of porphyrin-based dendrimers featuring conjugated fluorenyl dendrons is recalled herein and demonstrates the important role of the central core structure in determining linear and nonlinear optical properties. Further improvement of these properties seems possible with TAFlP-like structures based on observations made for dendrimers recently obtained. This makes the exploration of such new molecular architectures appealing for photodynamic therapy (PDT) and related applications.

A water soluble, phenanthroline-strapped zinc porphyrin bearing four arylsulfonate groups formed a stable host–guest complex with two per-O-methylated β-cyclodextrin cavities. In the host–guest assembly, the zinc porphyrin was capable of binding imidazole within the cavity between the zinc(II) ion and the phenanthroline strap in an aqueous medium. The formation of a hydrogen bond between the imidazole NH and the nitrogen atoms of the phenanthroline was an essential element of the binding event, as shown by comparative binding studies with a non-strapped tetrasulfonated zinc porphyrin and with N-methylimidazole. This hydrogen bonding in an aqueous medium was possible due to the protected hydrophobic environment created by the cyclodextrins around the phenanthroline strap. This type of binding event may provide a biomimetic approach to study water soluble heme protein models.

Tetraphenylporphyrin derivatives a synthetic heterocycles with convenient preparation and a richness of properties which make them attractive in broad fields such as energy, life and materials sciences. Thus, in the quest for new radical architectures, tetraphenylporphyrins are prime candidates. To this end, we designed free-base tetraphenylporphyrins bearing nitronyl and imino nitroxide moieties covalently bonded to the para-position of the meso-phenyl substituent. Their detailed synthesis and characterization are reported here.

During the past years, we focused on exerting control over the position and distance of porphyrins along our specifically designed oligonucleotidic scaffold. Indeed, in naturally occurring light-harvesting complexes, biopolymer scaffolds hold pigments at intermolecular distances that optimize photon capture, electronic coupling, and energy transfer. To this end, four uridine-porphyrin conjugates (a monomer, a dimer, a tetramer and an octamer) were subjected to a comprehensive conformational analysis by using NMR spectroscopy. The collected NOE NMR data highlighted characteristic and strong interactions indicating that the glycosidic angle between the ribose and uracil base is anti. In order to further investigate the conformation of this family of molecules, NMR experiments were carried out at variable temperatures. At low temperature, the signals of the porphyrinic protons decoalesce, showing two sets of β-pyrrolic protons. Similar observations are made for signals corresponding to sugar moieties and especially the H1′ protons, indicating molecular motions within our porphyrin-uridin arrays. These results testify in favor of the existence of a dynamic process between C3′-endo and C2′-endo conformations.

In-depth photophysical studies of four flexible covalent cages bearing either two free-base porphyrins or one free-base porphyrin and one Zn(II) porphyrin, connected by linkers of different lengths, are reported. In the case of the cages with two free-base porphyrins, exciton coupling between the porphyrins is evidenced by large and split Soret bands in the absorption spectra, but the different length of the linkers has only a slight effect on their emission properties. Strong electronic interactions between the porphyrins are also evidenced for the cages that incorporate a free-base porphyrin and a Zn(II) porphyrin, with a more pronounced splitting of the Soret band for the system with longer linkers. In these cages, following excitation of the Zn-porphyrin component, an almost quantitative energy transfer to the free-base unit occurs, with a rate 1.4 times faster in the cage with longer linkers (1.4 × 10¹¹ s^-1 vs. 1.0 × 10¹¹ s^-1). This difference might reflect the more flattened conformation adopted by the cage equipped with longer and more flexible linkers, the latter allowing for a shorter interplanar distance between the porphyrins. The results are discussed in terms of classical and short-range energy transfer mechanisms.

Looking for sustainable synthetic methodologies, mechanochemistry as a new tool for one-step and two-step approaches for the synthesis of meso-substituted porphyrins was explored. The best results were obtained in a two-step procedure, under liquid-assisted grinding in the oxidation step using 2-methyltetrahydrofuran, an environmentally acceptable solvent, and MnO₂ as a heterogeneous oxidant. The sustainability was assessed using two sustainability metrics, E-factor and EcoScale, which allow comparison between procedures and methods.

Benzimidazole phenol-porphyrin dyads have been synthesized to study proton-coupled electron transfer (PCET) reactions induced by photoexcitation. High-potential porphyrins have been chosen to model P680, the photoactive chlorophyll cluster of photosynthetic photosystem II (PSII). They have either two or three pentafluorophenyl groups at the meso positions to impart the high redox potential. The benzimidazole phenol (BIP) moiety models the Tyr_z-His190 pair of PSII, which is a redox mediator that shuttles electrons from the water oxidation catalyst to P680^•+. The dyads consisting of a porphyrin and an unsubstituted BIP are designed to study one-electron one-proton transfer (E1PT) processes upon excitation of the porphyrin. When the BIP moiety is substituted with proton-accepting groups such as imines, one-electron two-proton transfer (E2PT) processes are expected to take place upon oxidation of the phenol by the excited state of the porphyrin. The bis-pentafluorophenyl porphyrins linked to BIPs provide platforms for introducing a variety of electron-accepting moieties and/or anchoring groups to attach semiconductor nanoparticles to the macrocycle. The triads thus formed will serve to study the PCET process involving the BIPs when the oxidation of the phenol is achieved by the photochemically produced radical cation of the porphyrin.

Dihydroporphyrins or chlorins differ from porphyrins only by saturation of a peripheral double bond of the macrocycle. However, this small structural difference leads to a significant increase of the absorption band at approximately 650 nm, which makes them very interesting candidates for photodynamic therapy applications. The reduction of porphyrins bearing two, three or four pyridyl substituents with tin(II) chloride has been developed for the synthesis of dihydroporphyrins in yields of 15–73%. The reduction of 5-(aryl)-10,15,20-tris(2 or 4-pyridyl)porphyrin with tin(II) chloride dihydrate demonstrated good regioselectivity. Porphyrins with one meso-aryl bearing one electron-donating group (EDG) gave 5-aryl-10,15,20-tris(2- or 4-pyridyl)-17,18-dihydroporphyrins in 17–72% yield. Porphyrins with one meso-aryl bearing one or more electron-withdrawing groups (EWG) gave 5-aryl-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrins or 5-aryl-10,15,20-tris(4-pyridyl)-7,8-dihydroporphyrins in 15–21% yield and isobacteriochlorin. We have also proven the possibility of functionalizing these compounds to design new regioisomerically pure photosensitizers.

Targeting biotin receptors in cancer cells can improve specifying of photosensitizers (PSs) for cancer treatment by photodynamic therapy (PDT) applications. Consequently, there has been extensive research focusing mainly on the design of PSs with optimized pharmaceutical properties and better targeting toward cancer cells. Herein a tailored mono-biotinylated zinc(II) phthalocyanine (Pc-1) substituted with six phenoxy-bis(triazolyl) substituents has been synthesized. This Pc-1 has been further modified to its cationic version (Pc-2) through quaternizing of the triazole moiety to gain water solubility. Both non-ionic zinc(II) phthalocyanine (Pc-1) and its cationic derivative (Pc-2) were characterized by standard spectroscopic techniques, namely; FT-IR, ¹H and ¹³C NMR, UV-Vis and MALDI-TOF, and by elemental analysis. The photophysical and photochemical properties were evaluated in DMSO for the non-ionic Pc-1 and in both DMSO and water for the cationic Pc-2.

Thin films of metal phthalocyanines (M: Co, Zn, Ni) substituted with four 3,5-bis(2′,3′,4′,5′,6′-pentafluorobenzyloxy)benzyloxy groups have been prepared by the spin-coating technique. Optical properties and surface morphology of the thin films of metallophthalocyanines have been investigated as a function of organic solvents of acetone, chloroform, tetrahydrofuran, dimethylformamide and dimethylsulfoxide. Results show that optical properties and surface morphology of the prepared films depend on the type of organic solvent used.

Non-peripherally substituted metal-free and zinc phthalocyanines (Pcs) bearing four diethylamino groups and four Br atoms were prepared. Optimal conditions for synthesis of corresponding precursor (i.e. 3-bromo-6-(diethylamino)phthalonitrile) either by nucleophilic substitution or by Buchwald–Hartwig coupling were studied. Noteworthy, 3,6-bis(diethylamino)phthalonitrile was also formed, nevertheless only at low yield (typically below 1%) and all attempts for its cyclotetramerization failed. Q bands of prepared Pcs were strongly red shifted up to the near-IR region (769 and 800 nm in THF for zinc and metal-free Pc, respectively). Unusually large hypsochromic shifts of the Q bands, 130 and 80 nm for metal-free and zinc Pc, respectively, were observed upon treating these Pcs with trifluoroacetic acid, which was attributed to the protonation of non-peripheral amines. Treatment with sulfuric acid led to subsequent protonation on the azomethine nitrogens as well. Photophysical study revealed low fluorescence emission of both derivatives (Φ_F < 0.03, in THF) and efficient singlet oxygen production only for zinc Pc (Φ_Δ = 0.77 in THF and 0.60 in DMF).

4-[4-(1-Methyl-1-penylethyl)phenoxy]- and 4,5-di-[4-(1-methyl-1-phenylethyl)phenoxy]phthalonitriles are obtained by nucleophilic substitution. Mono- and double-decker lutetium and erbium complexes of 2(3),9(10),16(17),23(24)-tetrakis- and 2,3,9,10,16,17,23,24-octakis-[4-(1-methyl-1-phenylethyl)phenoxy]phthalocyanines are synthesized based on the phthalonitriles. Synthesized complexes are studied spectrophotometrically.

In an attempt to investigate its potential as a PDT ¹⁹F MRI molecular theranostic, a Zn phthalocyanine with 24 pseudo-equivalent fluorine atoms was designed and prepared. Compared to its H analogues, the fluorinated derivative has a much higher generation of singlet oxygen. ¹⁹F NMR signals in CDCl₃ showed that all the fluorine atoms are magnetically pseudo-equivalent with only two close fluorine signals. Formulation in PVP (polyvinylpyrrolidone), a FDA-approved additive, enabled water-solubilization of the phthalocyanines but no satisfying ¹⁹F NMR signal could be obtained, probably due to self-quenching caused by aggregation.

Electron-donating bromobenzenesulfanyl-group-substituted phthalonitrile derivative (1) and its novel non-peripherally tetra-substituted metal-free, indium and zinc phthalocyanine complexes (2–4) have been prepared for the first time. The chemical structures of this new phthalonitrile and its phthalocyanine derivatives were characterized by UV-vis, FT-IR, NMR, and MALDI-TOF mass spectrometry. The introduction of this electron-donating sulfanyl type of non-peripheral substituent accounts for a remarkable red shift of the phthalocyanine Q band to approximately 730 nm. Photophysical and photochemical properties of the novel functional complexes were also examined as photosensitizers for PDT applications.

Phthalocyanines (Pcs) are near-infrared photosensitizers with therapeutic potential for the treatment of bacterial infections and cancer. However, their clinical utility has been hindered by poor solubility in biological fluids, lack of specificity, and limited clearance from affected tissues. Glycosylated Pcs have the potential to overcome these issues by providing increased solubility and tumor specific targeting. However, reliable methods for their synthesis remains challenging. Here we present our first approach towards the synthesis of a series of silicon (IV) phthalocyanine conjugates bearing axial carbohydrate ligands (CPcCs). The novelty of our approach lies in the installation of axial alkyne ligands which can be functionalized with readily accessible acetyl protected azido glycosides, thus providing a modular approach for the synthesis of these complex macromolecules.

In this study, novel tetrasubstituted metallo- and metal-free phthalocyanines containing 7-hydroxy-4′-methoxyisoflavonoxy moieties at peripheral and non-peripheral positions have been prepared by cyclotetramerization of corresponding phthalonitriles. The most obvious feature of these quaternized complexes is their extensive solubility and non-aggregated species (especially non-peripherally substituted) in organic solvents such as chloroform, tetrahydrofuran, dimethylformamide and dimethylsulfoxide, which makes them candidates for use in many applications in different fields. The new compounds have been characterized by elemental analysis, FT-IR, UV-vis, ¹H and ¹³C NMR and MS (Maldi-TOF MS). Voltammetric and in situ spectroelectrochemical measurements have been performed with the aim of characterizing the electron transfer properties of the compounds on Pt in dimethylsulfoxide/tetrabutylammonium perchlorate, compared to those of previously reported corresponding compounds with tetra 6-hydroxyflavonoxy substituents. The effect of aggregation on the redox character of these complexes was also discussed.

Mono or diamino phthalocyanines with A3B or crosswise ABAB substitution patterns have been synthesized and used as building blocks for the preparation of dimeric and polymeric phthalocyanines. For this, 4,5-di(dodecylsulfanyl) phthalonitrile was converted into 1,3-diimino-6,7-di-(n-dodecylsulfanyl)-isoiminoindoline and then reacted with 6-nitro-1,3,3-trichloroisoindoline. The nitro functions on the resulting inseparable mixture of A3B and ABAB phthalocyanines were reduced into amines by Na₂S and the phthalocyanines could be chromatographically separated. Dimeric phthalocyanine was synthesized by the reaction of the mono-amino AB3 with sebacoyldichloride, and a poorly soluble linear polymeric material was obtained by reaction of the ABAB di-amino phthalocyanine with sebacoyl dichloride.

Tetra-zwitterionic-substituted nickel(II) phthalocyanine derivatives were newly synthesized starting from nonionic 2(3),9(10),16(17),23(24)-tetrakis-[2-(N-((3-dimethylamino)propyl) carbamate)oxyethyl)phthalocyaninato nickel (II). The novel compounds have been characterized by a combination of UV-vis, FT-IR and mass spectroscopies and elemental analysis. The critical micelle concentrations of the prepared compounds were measured, and the antioxidant activities were analyzed with radical scavenging ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). The zwitterionic molecules showed aggregated spectra in the UV-vis region, and they might be good surfactant candidates for the detergent industry with their appropriate critical micelle concentration (CMC) properties in water. The compounds exhibited ABTS radical scavenging activity and thus they have antioxidant activity.

New zinc(II) phthalocyanines (ZnPc-I and ZnPc-II) containing four peripheral anthracene pendant groups were synthesized by cyclotetramerization of (E)-4-(3-(4-((anthracen-9-yl-methylene) amino)phenoxy)propoxy)phthalonitrile and 4-(3-(4-((anthracen-9-ylmethyl)amino)phenoxy)propoxy) phthalonitrile. All compounds were characterized using a combination of analytical and spectroscopic techniques such ¹H, ¹³C NMR, FT-IR, UV-vis and MS spectral data. The molecular geometry and gauge including atomic orbital (GIAO) ¹H and ¹³C chemical shift values of the compounds in the ground state have also been calculated using B3LYP with the 6–31G(d) basis set. The chemical shift of the optimized molecular structure is compared with the experimental chemical shift values.

4,5-bis(3,5-bis(trifluoromethyl)phenoxy)phthalonitrile (1) and its complexes, namely 2,3,9,10,16,17,23,24-octakis[3,5-bis(trifluoromethyl)phenoxy] phthalocyaninato zinc(II) (2) and 2,3,9,10,16,17,23,24-octakis[3,5-bis(trifluoromethyl)phenoxy]phthalocyaninato indium(III) (3) are synthesized and characterized. Aggregation of the phthalocyanines was studied in tetrahydrofuran in different concentrations. Photochemical and photophysical properties of 2 and 3 in THF were investigated. A comparison between the photophysicochemical parameters of 2 and 3 yielded that 3 is a better photosensitizer than 2. The fluorescence quantum yields (Φ_F) and ¹O₂ formation (Φ_Δ) for compound 3 are 0.016 and 0.84, respectively. The values for compound 2 are 0.135 and 0.54, respectively. The values of indium and zinc phthalocyanines (2 and 3) could be classified as photosensitizers in the photocatalytic applications such as photodynamic therapy (PDT) of cancer.

Four asymmetric Zn(II) phthalocyanines (Pc1–Pc4) bearing a carboxylic acid group in the peripheral position have been designed and synthesized to investigate the influence of the distance between COOH group and the phthalocyanine core on their photophysical and photochemical properties. The novel phthalocyanine complexes were characterized by ¹H, ¹³C NMR, IR, and UV-vis spectroscopies, elemental analysis and matrix-assisted laser desorption ionization mass spectrometry (MALDI). The aggregation behavior, photophysical and photochemical properties such as fluorescence lifetime and quantum yields and singlet oxygen quantum yields of Pc1–Pc4 were explored in tetrahydrofuran (THF) to the determination of the potential use of these novel phthalocyanines as photosensitizers for different applications such as photovoltaic technologies and photodynamic therapy (PDT). Pc1–Pc4 exhibited high singlet oxygen generation quantum yields (0.84, 0.66, 0.88 and 0.65, respectively). Fluorescence quantum yields could be obtained for Pc1, Pc2, Pc3 and Pc4 (0.13, 0.31, 0.10 and 0.25, respectively) in THF.

In this work, 5-(trifluoromethyl)-2-thiopyridine substituted SiPc (1) and its quaternized derivative (2) were synthesized, and the effect of the linker sulfur atom on silicon phthalocyanines has been investigated for the first time in the literature. Both of the complexes have been characterized by standard spectroscopy methods. The complexes have good solubility in organic solvents and showed monomeric tendencies in all studied solvents. Only complex 2 had some aggregation in water because of solvent effects, as expected. In order to determine the therapeutic effect for cancer treatment, photophysicochemical properties were investigated in DMSO, DMF, toluene and water (for complex 2). The synthesized complexes were found to have about 3.5 times higher singlet oxygen quantum yields than the yields of unsubstituted SiPcCl₂ (Φ_Δ = 0.15 (in DMSO), 0.12 (in DMF), 0.10 (in toluene)) because of the effects of bulky axial groups.

Unsymmetrical metal-free phthalocyanine was synthesized through cyclotetramerization of 4-[2,6-dimethyl-4-(4-tert-butyl-phenylazo)phenoxy]phthalonitrile and 4-(hexylthio)phthalonitrile in the presence of lithium in n-pentanol, then metal-free phthalocyanine was obtained by acidification with acetic acid. Finally, metalation was achieved by refluxing metal-free phthalocyanine in n-pentanol in the presence of zinc (II) salt. The structure of synthesized phthalocyanine derivatives were characterized by using proton nuclear magnetic resonance, mass spectrometry, ultraviolet–visible spectroscopy, and Fourier transform infrared spectroscopy. The HOMO–LUMO energies were computed using density functional theory. The HOMO–LUMO energy difference is 2.28 eV. The calculated results were consistent with the experimental data. In addition, aggregation behaviors and general trends for photophysical properties of these phthalocyanine derivatives were studied in tetrahydrofuran. The emission intensities of these phthalocyanine derivatives were strongly quenched by 1,4-benzoquinone in tetrahydrofuran.

The preparation and structural characterization of a pair of scandium(III) phthalocyanine hydroxide complexes were achieved by reaction of PcScCl with alkali metal alkoxides, likely via hydrolysis of soluble PcSc-alkoxide intermediates. A Sc₂Li₂(μ₃-OH)₄ cubane supported by two distorted Pc rings of the form (PcSc)₂(μ₃-OH)₄Li₂(THF)(DME) was isolated from the reaction of PcScCl with LiOⁱPr, while a simpler alkali-metal-free [Pc₂Sc₂(μ₂-OH)₂(THF)] was obtained from addition of NaO^tBu; both structures are reminiscent of bent metallocenes, with dihedral angles between the two Pc rings of 50.8 and 37.7° respectively. A soluble PcScOH material can also be obtained directly via hydrolysis of insoluble PcScCl in approximately 95:5 THF:water. Reduction of the Pc ring of PcScCl using KC₈ is reversible and generates Pc^3- and Pc^4--containing materials that were characterized via UV-vis spectroscopy and, where appropriate EPR and ¹H NMR spectroscopy; analogous reductions of the PcScOH-based species were irreversible. Exposure of the air-sensitive, reduced PcScCl-based species to ambient atmosphere generated PcScOH materials analogous to the direct hydrolysis route.

In this study, the synthesis and characterization of mono-(phthalocyaninato) lutetium(III) (1-Cl and 1-F) [Lu^III(AcO)(Pc)] (Pc = phthalocyaninato, AcO = acetate) and bis-(phthalocyaninato) lutetium(III) (2-Cl and 2-Br) [Lu^IIIPc₂] bearing halogenated (F, Cl and Br) phenoxy–phenoxy groups are described and verified by IR, ¹H-NMR, UV-vis and mass spectrometry. Photochemical and photophysical properties of 1-F, 1-Cl, 2-Cl and 2-Br in DMSO are also presented. A comparison between photophysical and photochemical parameters of mono and bis derivatives showed that mono phthalocyanines are better photosensitizers than bis phthalocyanines. Photophysical and photochemical properties of phthalocyanines are very useful for photodynamic therapy applications. Singlet oxygen quantum yields (Φ_Δ) give an indication of the potential of the complexes as photosensitizers in photodynamic therapy applications. The chloro, fluoro, bromo-phenoxy–phenoxy substituted mono-(phthalocyaninato) lutetium(III) complexes (1-Cl and 1-F) gave good singlet oxygen quantum yields (from 0.86 to 0.80) in DMSO. Thus, these complexes show potential as Type II photosensitizers for PDT of cancer.

In this manuscript, we have studied the selectivity in the complexation of fullerene species by a Fe2Pc3 metallo-organic helicate (1) assembled using a bidentate phthalocyanine (Pc) as ligand. The large aromatic internal surface of this helicate shows a strong selectivity towards the encapsulation of C₇₀ from a mixture of C₆₀ and C₇₀. On the other hand, a bisimidazole-containing naphthalenediimide was used to perform guest exchange experiments over [fullerene ⊂ 1] complexes, taking advantage of the strong coordination bond of the imidazole ring to the Zn centers in the Pc cavity.

Our laboratory started research on tetraazaporphyrins in the middle of the 1970s. Before our works there was no information in the literature about coordination and ionization properties of these compounds, formation of their metal complexes or their state and behavior in proton-donating and proton-acceptor media. We carried out the first studies of the coordination and acid-base properties of unsubstituted tetraazaporphine [1], its octaphenyl [2] and tetra(tetramethylene)-[3] substituted derivatives. In this micro-review we summarize our works on the peripheral functionalization of unsubstituted porphyrazines and on their acid-base and coordination properties.

Cobyric acid and cobinamide are valuable building blocks for the synthesis of artificial cobalamins modified at the nucleotide loop. However, truncated vitamin B12 derivatives are devoid of the phosphate group. We have found that 2-iodoxy benzoic acid-mediated phosphorolysis leads to the cleavage of only one of the phosphodiester bond giving a vitamin B₁₂ analogue with the phosphate moiety preserved. Subsequent alkylation with an organic halide establishes its role as a precursor for the synthesis of vitamin B12 mimics modified at the nucleotide loop.

Unlike N-confused porphyrins which are well-known and extensively studied tetrapyrroles, N-confused hydroporphyrins are almost unknown, largely because so far they have resisted attempts at rational synthesis. Here, we report our efforts towards the total synthesis of N-confused hydroporphyrins. We have prepared N-confused building blocks analogous to the non-N-confused substrates in the Lindsey synthesis of sparsely substituted chlorins. We have systematically flipped the A, B and C pyrrole rings in the dipyrrolic precursors of the target N-confused macrocycles, preparing in total an N-confused “Western half” (tetrahydrodipyrrin) and two N-confused “Eastern halves” (brominated formyldipyrromethanes). These were subjected to a range of cyclization conditions. While we successfully isolated and identified three macrocyclic products, none of these proved to be the desired N-confused hydroporphyrin.

We report syntheses of thiophene and dithiophene-substituted porphycenes (ThPc and DThPc) at 2,7,12,17-positions by McMurry coupling. The crystal structure of ThPc revealed that the porphycene plane shows a highly planar structure, and the dihedral angles between the porphycene core and thiophene are relatively small at 21° and 18°. ThPc and DThPc exhibit red-shifted and broadened absorption because of the extension of π conjugations through porphycene to the substituted thiophenes. We found that introduction of thiophene units onto porphycene results in decreasing the HOMO–LUMO differences effectively.

An expanded heterocorrole, meso-tetraaryl-tellura[22]porphyrin(6.1.1.0), containing a bipyrrole moiety and a six-carbon long link, has been synthesized. The reaction path proceeds through a controlled acid-promoted extrusion of one tellurium atom from meso-aryl-26,28-ditellurasapphyrin, leading to a structure where one tellurophene ring of the substrate is replaced by a bridging acyclic four-carbon unit. This aromatic porphyrin-annulene hybrid is conformationally flexible in solution, on account of the C4 unit adopting two different configurations: trans–cis–trans or all-trans. Studies of the dynamic behavior of tellura[22]porphyrin(6.1.1.0) in solution were performed by means of ¹H and ¹²⁵Te NMR spectroscopy. The X-ray structure of the all-trans form with trapezoid macrocyclic skeleton is also presented.

Propentdyopents are naturally occurring dipyrroles deriving from the metabolism of heme and characterized by a dipyrrin-1,9-dione motif. The unusual name propentdyopent is due to the first colorimetric method (the Stokvis reaction) for the detection of these compounds, which were initially isolated from urine samples. Upon reduction in alkaline solutions, they produced red species that were termed pentdyopents to describe with Greek numerals their absorption maximum (525 nm) in the visible range. The precursors to the red pentdyopents were thus indicated as propentdyopents. Over the course of several decades, these dipyrrolic compounds have appeared in several studies of human physiology, typically associated to conditions of abnormal heme metabolism and/or oxidative stress. Concurrently, synthetic investigations have confirmed their chemical structure, reactivity, and ability to coordinate metals as bidentate monoanionic ligands. Notably, the planar dipyrrindione platform can undergo reversible one-electron redox processes and thereby act as an electron reservoir in metal complexes. In combination with the documented ability of the carbonyl groups to act as hydrogen-bonding acceptors, the coordination chemistry of propentdyopents could lead to new applications for this old class of pigments. Furthermore, the observation of these pigments in several clinical contexts could potentially delineate a role of propentdyopents as diagnostic biomarkers. This mini-review summarizes both the chemistry and biology of propentdyopents while highlighting the ample space for new discoveries.

The controlled synthesis of oligoaromatics can provide materials of wide utility. Here, we describe the preparation of higher order oligoheterocycles via a tandem Suzuki cross-coupling protocol. This method has allowed for the iterative construction of fluorescent α,α′-linked penta- and septaheterocyclic systems with modification of the terminal moiety allowing for fine-tuning of the emission features.

Porphyrins are prominent host molecules which are widely used due to their structural characteristics and directional interaction sites. This review summarizes non-covalently bound ternary complexes of porphyrins, constructed from at least three non-identical species. Progress in supramolecular chemistry allows the creation of complex molecular machinery tools, such as rotors, motors and switches from relatively simple structures in a single self-assembly step. In the current review, we highlight the collection of sophisticated molecular ensembles including sandwich-type complexes, cages, capsules, tweezers, rotaxanes, and supramolecular architectures mediating oxygen-binding and oxidation reactions. These diverse structures have high potential to be applied in sensing, production of new smart materials as well as in medical science.

Porphyrins and phthalocyanines are widely studied molecules for various functional applications. Researchers have investigated these photoactive compounds for electrochemical, sensor, semiconductor and photodynamic therapy purposes. Layer-by-layer (LbL) self-assembly is preferred for its simple, environmentally-friendly and water-based features compared to other coating techniques in the literature. Coating thickness can be controlled on the order of nanometers by LbL mechanism. Multilayer thin film formation of diverse phthalocyanine-based molecules is examined in terms of molecular orientation and temperature dependency by the LbL method. However, as well as concentration and temperature, the pH of the coating medium is another challenging parameter in the LbL approach. Film thickness and layer distribution are influenced by pH value, changing ionic density and hence the strength of electrostatic interactions during LbL assembly. In this study, layer-by-layer deposition of branched poly(ethyleneimine)/nickel(II)phthalocyanine-tetrasulfonic acid tetrasodium salt (NiPcTS) coating pair is studied. Impact of pH and concentration of NiPcTS on thin film properties are tested for four different pH conditions. Corresponding analysis is made by UV-vis spectroscopy, surface profiler and quartz-crystal microbalance. LbL deposition of NiPcTS is homogeneously controlled and 98 nm thick films are obtained in the presence of acidic media.

The reactivity of two phenolic porphyrins bearing respectively catechol and gallol-derived meso substituents (5,10,15,20-tetrakis(3,4-dihydroxyphenyl)porphyrin and 5,10,15,20-tetrakis(3,4,5-trihydroxyphenyl)porphyrin) with trivalent metallic ions (Fe, Mn, In) was studied. Six supramolecular compounds were obtained and structurally characterized by single crystal X-ray diffraction. In each compound, the supramolecular assembly was based on the axial coordination of a phenolate function to the metallic ion lying in the porphyrinic core. A great diversity of supramolecular architectures was accessible through such simple arrangements, and objects ranging from dimers to one-dimensional polymers were isolated. Some of these assemblies were further investigated in solution by mass spectrometry and by UV-vis absorption spectroscopy. For the iron-based materials, the redox behavior was studied in solution through cyclic voltammetry experiments in inert conditions and under air.

Mechanical properties of six different binary ionic porphyrin crystals with variable morphologies were measured and correlated with their structural properties. These solids were formed from stoichiometric combinations of negatively charged tectons, meso-tetra(4-sulfonatophenyl) porphyrin (TSPP), Cu(II) meso-tetra(4-sulfonatophenyl)porphyrin (CuTSPP), Ni(II) meso-tetra (4-sulfonatophenyl)porphyrin (NiTSPP), and four different cationic tectons, namely, meso-tetra (4-pyridyl)porphyrin (TPyP), tetra(N-methyl-4-pyridyl)porphyrin (TMPyP), Cu(II) meso-tetra(Nmethyl- 4-pyridyl)porphyrin (CuTMPyP), Ni(II) meso-tetra(N-methyl-4-pyridyl)porphyrin (NiTMPyP), and tetra(4-aminophenyl)porphyrin (TAPP). Crystal structures were determined from single crystal and powder X-ray diffraction patterns. Scanning electron and atomic force microscopes (SEM and AFM) provided topographical information. The common arrangement of the porphyrin tectons within the crystals is consistent with alternating face-to-face molecular arrangement forming coherent columns along the fast-growing long axis which are held together by electrostatic and π–π interactions as well as hydrogen bonding. In acquiring the indentation data of the porphyrin crystals using AFM, stress was applied perpendicular to the direction where ionic and π–π bonds dominate the packing. At indent loads ≤50 nN/nm², all the porphyrin structures deformed elastically. Young’s modulus (E) values for the different crystals range from 6 to 28 GPa. In a broader perspective, this study highlights the extraordinary mechanical behavior of porphyrin assemblies formed by ionic self-assembly. Judicious selection of charged porphyrin synthons can yield crystalline materials with mechanical properties that combine the elastic characteristics of ‘soft’ polymers with the stiffness of composite materials. Such high-performance materials are excellent candidates for deformable optoelectronic devices.

The generation of singlet oxygen (SO), primarily by using a combination of light and photosensitizers in the presence of a dissolved gas, finds applications in both chemistry and medicine. The efficiency of its formation can be enhanced by immobilization of the photosensitizers. In this work, we have explored the covalent functionalization in suspension of hexahedral slab-like polysilicon microparticles (μP, with a largest dimension of three microns) with a model photosensitizer, 5-(4-isothiocyanatophenyl)-10,15,20-(triphenyl)porphyrin (ITC-P), and evaluated the singlet oxygen generation of this photosensitizer in solution and after immobilization (ITC-P-μP) in suspension. The SO-detection experiment on the functionalized microparticles was performed using a hydrogel as the matrix supporting the microparticles (to avoid their settling), and revealed that ITC-P-μP in suspension is capable of generating SO more efficiently than free ITC-P in solution.

Stable porphyrin films expressing specific chirality at a supramolecular level have been achieved by Langmuir–Blodgett (LB) deposition of two inherently chiral (L)-proline porphyrin derivatives. Spectroscopic measurements (UV-vis, CD and fluorescence) evidenced that the stereogenic center stored on the peripheral proline residue dictates the specific supramolecular organization of the macrocycles at the air/water interface, which is found to be significantly different from that observed in solution (i.e. EtOH/H₂O 25/75, v/v solvent mixture). In the case of free-base porphyrin, the firmness as well as the homogeneity of the corresponding chiral LB films are not optimal for a number of layers below 10. For the zinc derivative, thermal annealing helps to make the films more oriented and produces an amplification of the chirality of the treated films. The results described are of relevance, for example, for the development of stereoselective sensors, where the fabrication of chiral surfaces with specific and reproducible stereochemistry represents a crucial issue.

A pH-driven self-assembly of a simple aza-BODIPY was discovered in PBS solution, whereby ion-specific J-aggregated nanostructures were generated at very low dye concentration (2.5–20 μM). The aggregation process was investigated in different conditions (pH, temperature and time) by monitoring absorption spectral shifts and associated nanostructure morphological changes. The pH-driven self-assembly process demonstrated an instantaneous thermodynamic phenomenon associated with three characteristic structures, each with distinctive optical properties. When the sample was first formulated within a short time window, a thermodynamically less stable intermediate with an unusual morphology of triangular nanoplates and broad absorption was observed. The formation of these structures was independent of the ions in PBS solution (Na⁺, K⁺), thus indicating that the triangular structure was inherent to the anisotropic structure of aza-BODIPY scaffolds. The second structure associated with a metastable pathway generated a uniform population of spherical nanovesicles, while the third structure, generated through a more thermodynamically stable pathway consisted of fibers. The absorption spectra suggested that both spherical and fiber structures contributed to the J-aggregation band at 735 nm in the near infrared optical spectrum and their population in each formulation was concentration dependent. The results highlighted the significance of ion effects in self-assembly of aza-BODIPY and the mechanistic structural changes of the morphology. Furthermore, this fundamental discovery offers a versatile method for the self-assembly of aza-BODIPY J-aggregates as a new nanoplatform with potential photonic applications.

Porphyrins and metalloporphyrins are one of the most widely studied platforms for the construction of supramolecular structures. These compounds have an extended aromatic system that allows π–π stacking interactions which, together with hydrogen bonds, electrostatic forces and the formation of inter-metallic complexes arising from peripheral groups, offer a versatile platform to control the self-assembly mechanism. In this work, we present the study of nanostructures formed by self-assembly of the water-soluble porphyrins meso-tetra(N-methyl-4-pyridyl)porphyrin (TMPyP) and meso-tetra(4-sulfonatophenyl)porphyrin (TPPS) in the presence of hard nanotemplates. Different nanoparticles (silica, gold, and polystyrene), concentrations and synthetic procedures were explored. The obtained materials were characterized by SEM and AFM microscopies, UV-vis absorption spectroscopy and dynamic light scattering measurements. A clear modification of the SiO₂ NP surface roughness using one-pot synthesis was observed. The results were variable depending on the porphyrin–surface interactions and concentrations used. At lower porphyrin concentrations, a shift of the Soret band was observed, while at higher concentrations, free NS were formed. This reflects a competition between surface and solution directed self-assembly.

The coordination of the chiral metalloporphyrin ([5,10,15,20-[4-(R,R,R,R)-2-N-octadecylamidoethyloxiphenyl] porphyrin] zinc (II)) and an achiral homologue to an amphiphilic block copolymer of poly(styrene-b-4-vinyl pyridine) (PS-b-P4VP) have been studied in solution and as cast material. The resulting chiral dye-polymer hybrid material has been accomplished via axial coordination between the zinc (II) metal ion in the core of the porphyrin ring and the pyridyl units of the block-copolymer in a non-coordinative solvent. The supramolecular organization and possible chirality transfer to the hybrid material have been studied in solution by UV-visible absorption spectroscopy, fluorescence spectroscopy, Nuclear Magnetic Resonance and Circular Dichroism. The morphology of the chiral and achiral doped polymers has been studied in solid state by Transmission Electron Microscopy and Atomic Force Microscopy. We show that the nanostructures formed depend greatly upon the nature of the side-chains on the porphyrins, where a chiral group leads to a very homogeneous phase-separated material, perhaps indicating that chiral side groups are useful for the preparation of this type of supramolecular hybrid.

Porphyrin nanorods were prepared by ion-association between free-base meso 5,10,15,20-tetrakis-(4-N-methylpyridinium)porphyrin cations and tetraphenylborate anions. The nanorods have variable lengths (up to a few micrometers long) and diameters (~50–500 nm). Their structure at the molecular level was elucidated by combining multinuclear solid state NMR spectroscopy, synchrotron X-ray powder diffraction and DFT calculations.

Manganese porphyrins are of interest due to the optical, electronic and magnetic properties of the central metal ion, coupled to the low bandgap of the polyaromatic ring. These attractive characteristics are harnessed in solutions or in ultra-thin films, such as, for example, self-assembled monolayers. However, for devices, thicker films deposited using a controlled and reproducible method are required. Here we present the morphological, structural, chemical and optical properties of manganese(III) tetraphenylporphyrin chloride (MnTPPCl) thin films deposited using organic molecular beam deposition, typically employed to process analogue molecules for applications such as organic photovoltaics. We find, using a combination of UV-vis and X-ray photoelectron spectroscopies, that the sublimation process leads to the scission of the Mn–Cl bond. The resultant film is a Mn(II)TPP:Mn(III)TPPCl blend where approximately half the molecules have been reduced. Following growth, exposure to air oxidizes the Mn(II)TPP molecule. Through quantitative analysis of the time-dependent optical properties, the oxygen diffusion coefficient (D) ~1.9 × 10^-17 cm²/s is obtained, corresponding to a slow bulk oxidation following fast oxidation of a 8-nm-thick surface layer. The bulk diffusion D is lower than for analogous polycrystalline films, suggestion that grain boundaries, rather than molecular packing, are the rate-limiting steps in oxidation of molecular films. Our results highlight that the stability of the axial ligands should be considered when depositing metal porphyrins from the vapor phase, and offer a solvent-free route to obtain reproducible and smooth thin films of complex materials for engineering film functionalities.

Unveiling the interplay of semiconducting organic molecules with their environment, such as inorganic materials or atmospheric gas, is the first step to designing hybrid devices with tailored optical, electronic or magnetic properties. The present article focuses on a double-decker lutetium phthalocyanine known as an intrinsic semiconducting molecule, holding a Lu ion in its center, sandwiched between two phthalocyanine rings. Carrying out experimental investigations by means of electron spectroscopies, X-ray diffraction and scanning probe microscopies together with advanced ab initio computations, allows us to unveil how this molecule interacts with weakly or highly reactive surfaces. Our studies reveal that a molecule–surface interaction is evidenced when molecules are deposited on bare silicon or on gold surfaces together with a charge transferred from the substrate to the molecule, affecting to a higher extent the lower ring of the molecule. A new packing of the molecules on gold surfaces is proposed: an eclipse configuration in which molecules are flat and parallel to the surface, even for thick films of several hundreds of nanometers. Surprisingly, a robust tolerance of the double-decker phthalocyanine toward oxygen molecules is demonstrated, leading to weak chemisorption of oxygen below 100 K.

Dyad compounds in which a fullerene (C₆₀) was covalently linked to a monocationic porphyrin at a N,N′-bridge substituent, were synthesized by condensation reaction. The low solubility of a dyad containing tetraphenylporphyrin (TPP) derivative was improved by using octaethylporphyrin (OEP) derivatives and introduction of an alkyl substituent to the porphyrin derivatives. The energy levels of the frontier orbitals, estimated experimentally using potentiometric data and the optical energy band gaps obtained by the UV-vis spectra, were sufficiently low to be comparable to acceptor materials. They varied depending on the peripheral substituents on the porphyrin unit. DSC analysis of the drop-cast films of the P3HT/dyad blends showed that the film containing the OEP dyad, annealed at a higher temperature, had more amorphous fractions than the films containing the TPP dyad.

The encapsulation of five derivatives of chlorin e6 with different hydrophobicity and aggregation properties into a series of five poloxamer-type triblock copolymer micelles (BCMs) with varying numbers of polyethylene and polypropylene glycol (PEG, PPG) units was monitored using ¹HNMR spectroscopy. NMR chemical shift and line shape analysis, as well as dynamic methods including diffusion ordered spectroscopy (DOSY) and T₁ and T₂ relaxation time measurements of the chlorin and the polymer resonances, proved useful to assess the chlorin–BCM compatibility. The poloxamers had high capability to break up aggregates formed by chlorins up to intermediate hydrophobicity. Physically entrapped chlorins were always localized in the BCM core region. The loading capacity correlated with chlorin polarity for all poloxamers among which those with the lowest number of PPG units were most efficient. DOSY data revealed that relatively weakly aggregating chlorins partition between the aqueous bulk and micellar environment whereas more hydrophobic chlorins are well retained in the BCM core region, rendering these systems more stable. T₁ and T₂ relaxation time measurements indicated that motional freedom in the BCM core region contributes to encapsulation efficiency. The BCM corona dynamics were rather insensitive towards chlorin entrapment except for the poloxamers with short PEG chains. The presented data demonstrate that 1H NMR spectroscopy is a powerful complementary tool for probing the compatibility of porphyrinic compounds with polymeric carriers such as poloxamer BCMs, which is a prerequisite in the development of stable and highly efficient drug delivery systems suitable for medical applications like photodynamic therapy of tumors.

In-plane electrical characteristics of non-peripherally octyl(C₈H₁₇)- and hexyl(C6H13)- substituted liquid crystalline (LC) double decker lanthanide bisphthalocyanine (LnPc₂) complexes with central metal ions lutetium (Lu), and gadolinium (Gd) have been measured in thin film formulations on interdigitated gold (Au) electrodes for the applied voltage (V_a) range of 0 ≤ V_a ≤ 100 V. The conduction mechanism is found to be Ohmic within the bias of 0 ≤ V_a ≤ 30 V, while the bulk limited Poole–Frenkel mechanism is responsible for the higher bias. The compounds show individual characteristics depending on the central metal ions, substituent chain lengths and their mesophases. Values of 67.55 μScm^-1 and 42.31 μScm^-1 have been obtained for room temperature in-plane Ohmic conductivity of as-deposited octyl lutetium (C₈LuPc₂) and hexyl gadolinium (C₆GdPc₂) films, respectively while C₈GdPc₂ films exhibit nearly two orders of magnitude smaller conductivity. On annealing at 80 °C, Ohmic conductivities of C₈LuPc₂ and C₈GdPc₂ are found to have increased but the conductivity of C₆GdPc₂ decreased by more than one order of magnitude to 1.5 μScm^-1. For physical interpretation of the charge transport behavior of these three molecules, their UV-vis optical absorption spectra in the solution and in as-deposited and annealed solid phases and atomic force microscopy study have been performed. It is believed that both orientation and positional reorganizations are responsible, depending upon the size of the central ion and side chain length.

A unique organic/inorganic nanocomposite of non-aggregated lead sulphide (PbS) quantum dots (QDs) dispersed within a spun film of non-peripherally octakis(hexyl)-substituted metal-free phthalocyanine (C₆H₂Pc) has been prepared at room temperature by a simple and low-cost method. The frequency response of alternating current (AC) conduction in a 130 nm thick C₆H₂Pc/PbS film sandwiched between the indium-tin-oxide (ITO) and aluminum (Al) electrodes is found to obey the universal power-law. The cryogenic study of AC conduction reveals that the correlated barrier hopping (CBH) model closely fits to the experimental data at temperatures below 240 K. The parameters obtained by fitting the CBH model point out that the hopping process cannot take place directly between neighboring PbS QDs but involves the localized states within the matrix.

We report a low-cost sensing platform for effective naked-eye detection of fluoride ion in aqueous media. The sensor is based on silicon complex of 5,10,15-tritolylcorrole (SiTTCorr) deposited on paper support and designed in a particular way that permits it to perform in a unique sensing event an internal sensor self-calibration and subsequent analysis of fluoride ion in a concentration range from 20 μg/L to 200 mg/L with a LOD 9 μg/L, much lower than the WHO guideline value of 1.5 mg/L for fluoride in drinking water. The influence of tetradodecylammonium chloride (TDACl) anion exchanger addition to the performance of SiTTCorr-based sensors was studied and the sensor with optimal ionophore: exchanger = 2:1 ratio demonstrated the highest sensitivity. The evident color variation of SiTTCorr-based optode from dark pink to intense green occurred upon addition of increasing concentrations of fluoride. A smartphone application equipped with home-written color intensity analysis software as a detector of developed sensor output permitted fluoride content quantification in bottled water and toothpaste samples. Moreover, since at the quantification step the SiTTCorr color variation was significant for the red component of visible light and increase of fluoride content evidently changed this color from red to yellow and then to green, the developed optode was compared to a kind of chemical traffic light, able to detect the presence of fluoride in permitted, borderline or dangerous concentrations, respectively.

Compound (4,4′-hex-3-ene-3,4-diyl)bis(4,1-phenylene)bis(oxy)diphthalonitrile 3 was synthesized by the reaction of 4-nitrophthalonitrile 1 and diethylstilbestrol 2 in dry DMF in presence of dry K₂CO₃. New mononuclear phthalocyanines 4–6 were obtained from compound 3 by addition of the corresponding metal salts [Co(OAc)₂ · 4H₂O, Zn(OAc)₂ · 2H₂O and Cu(OAc)₂]. The novel compounds were characterized by elemental analysis and FT-IR, UV-vis, 1H-NMR and MALDI-TOF mass spectroscopy techniques. The effects of four main groups of organic vapors on these novel compounds were studied and discussed. The adsorption kinetics of alkanes (n-hexane and n-octane), alcohols (methanol and 2-proponal), chlorinated hydrocarbons (dichloromethane and trichloromethane) and amines (diethylamine and triethylamine) on 4–6 were examined using three adsorption kinetic models: the Elovich equation, the pseudo-first-order equations and Ritchie’s equation. Results show that the linear regression analysis with respect to the pseudo-second-order rate equations generates a straight line that best fits the data of adsorption of alcohols and chlorinated hydrocarbons on Pc films. On the other hand, the Elovich equation generates a straight line that best fits the data of adsorption of alkanes and amines.

Two novel axially-substituted asymmetric silicon (IV) phthalocyanines, the first one substituted with both polyethylene glycol and indomethacin groups (Pc1) and second one substituted with both polyethylene glycol and mefenamic acid groups (Pc2) have been designed and synthesized for the purpose of pH sensing examinations. Their absorption and fluorescence emission-based spectral properties were investigated in chloroform, tetrahydrofuran and toluene. The pH-sensing properties of Pc1 and Pc2 were examined in detail by using UV-vis absorption and fluorescence spectroscopies in tetrahydrofuran. The effects of the substituents on the spectroscopic properties and pH-sensing behavior of these silicon phthalocyanines were revealed. Pc1 didn’t show a pH response; however, Pc2 exhibited a signal increase from pH 5.40 to 0.37 (turn on) and a drastic quenching when pH went from 0.37 to 5.40 (turn off). The protonation/deprotonation stage of the NH group of Pc2 presented fluorescence-based “on-off” type molecular switch properties.

The synthesis and characterization of novel asymmetric zinc(II) phthalocyanines (4–9) and their linking through peripheral and nonperipheral positions on the phthalocyanine ring via click coupling to alkyne-functionalized 2,3,6,7,10,11-hexakis(prop-2-ynyloxy)triphenylene core are described for the first time. These phthalocyanines (Pcs) (4–12) were characterized by elemental analysis and different spectroscopic techniques such as UV-vis, ¹H-NMR, FT-IR and mass spectroscopy. Furthermore, the utilization of thin films of novel Pcs as a sensitive layer for detection of lung cancer from exhaled human breath at room temperature under exposure to marker volatile organic compounds (VOCs) are presented. The developed sensors were tested for acetone, ethanol, n-hexane, toluene, chloroform and isoprene in a range of 300–14560 ppm. The obtained results have confirmed the possibility of utilization of Pc-based Surface Acoustic Wave (SAW) sensors for medical diagnosis based on exhaled breath analysis.

Two asymmetrical amphiphilic phthalocyanines simultaneously containing hydrophobic alkoxy and hydrophilic 15-crown-5-ether substituents at the phthalocyanine periphery H₂{Pc(15C5)₃[(OC₈H₁₇)₂]} (Pc-1) and H₂{Pc(15C5)[(OC₈H₁₇)₆]} (Pc-2) and their symmetrical analogue H₂[Pc(OC₈H₁₇)₈] (Pc-3) have been synthesized and characterized. The _Pc-n/CdS (n = 1, 2 and 3, respectively) hybrid films are obtained successfully via a simple quasi-Langmuir–Shäfer (QLS) method using H₂S-vapor annealing over the Pc-n/Cd²⁺ self-assembled film formed at the interface of the air/CdCl₂ aqueous solution. The film-structure and properties of both the hybrid Pc-n/CdS and pure Pc-n films are comparatively studied by a wide range of methods including UV-vis, polarized UV-vis, XRD, SEM and I–V measurements. Experimental results exhibit a slipped co-facial stacking mode in an “edge-on” conformation (H-type aggregate) formed for the phthalocyanine molecules in both pure Pc-n films and the corresponding Pc-n/CdS hybrid films, with increasing intermolecular π–π interactions in the order of Pc-n < Pc-n/CdS and Pc-3/CdS < Pc-2/CdS < Pc-1/CdS, respectively. Accordingly, filmmicrostructures, crystallinity and conductivity are effectively improved by introducing CdS nanoparticles into the 15-crown-5-substituented phthalocyanines forming Pc-1/CdS and Pc-2/CdS hybrid films. These render excellent sensing performance towards NO₂ in the 0.05–2.5 ppm range within a fast dynamic exposure period of 30 s. Strikingly, Pc-1/CdS hybrid film presents an unprecedented high sensitivity of 157.3%.ppm^-1 vs. very low NO2 concentration range of 0.05~0.25 ppm, achieving one of the best room temperature sensing performances in terms of high sensitivity, rapid responsibility and low detection limit among self-assembled film-based NO₂ sensors.

Meso-5,10,15,20-tetrakis-3,5-di-tert-butyl-4-oxocyclohexadienylideneporphyrinogen, OxP, is a versatile, highly colored chromophore derived from meso-5,10,15,20-tetrakis(3,5-di-tertbutyl-4-hydroxyphenyl)porphyrin. It exhibits a wide range of chromogenic responses to solvents (solvatochromism), anions and acidic media (halochromism) making it potentially useful as an analytical reagent. The chromogenic responses of OxP can be modulated by varying its chemical structure, and this is reviewed here based on the introduction of substituents at central nitrogen atoms or pyrrolic β-positions. OxP and its N-alkylated derivates Bn₂OxP and Bn₄OxP have been used to estimate acidity in non-polar solvents. Bn₂OxP can also be used to determine enantiomeric excesses of chiral substances. N-alkylation has also been used to introduce higher functional groups such as porphyrins to prepare self-assembling systems. β-Substitution has been used to introduce selectivity of anion interactions including towards basic anions (fluoride, cyanide) and polyoxoanions (nitrate, perchlorate, etc.). These aspects make OxP a highly adaptable tetrapyrrole molecule for sensing and other applications.

This paper proposes pattern recognition of gastric cancer biomarkers CEA, CA19-9 and p53 in whole blood and urine samples using a stochastic sensor based on exfoliated graphene (E-NGr) paste modified with protoporphyrin IX. The proposed sensor covered large ranges of concentrations: 1 × 10^-12–1 × 10^-7 μg/mL for CEA, 1 × 10^-13–1 × 102 U/mL for CA19-9, and 0.2–5.0 μg/mL for p53. These ranges allowed the determination of the three biomarkers from early to latest stages of gastric cancer. Validation of the pattern recognition of gastric cancer biomarkers was accomplished using biological samples: whole blood and urine.

A new hybrid material has been developed by mixing a sandwich-type double-decker, Eu[Pc(OC₄H₉)₈]₂ = 2,3,9,10,16,17,23,24-octabutoxyphthalocyaninate] with acidified multiwalled carbon nanotubes (aMWCNTs) through non-covalent interactions. The UV-vis spectrum, X-ray diffraction and scanning electron microscope have been employed to reveal the J-aggregate mode and optimized morphology of Eu[Pc(OC₄H₉)₈]₂ molecules in the Eu[Pc(OC₄H₉)₈]₂/aMWCNTs hybrid material. The gas-sensing devices based on this hybrid material are fabricated by a simple solvent-processing quasi-Langmuir–Shäfer (QLS) progress. The n-type and p-type response is shown by the Eu[Pc(OC₄H₉)₈]₂/aMWCNTs hybrid film at room temperature. The detection limit of the hybrid for ammonia and nitrogen dioxide gas is 0.5 ppm and 0.3 ppm, respectively.

The synthesis of the porphyrin-calix[4]arene conjugates was carried out using the Pd(0)-catalyzed amination of Zn(II) meso-(3-bromophenyl)porphyrinate with bis(3-aminopropoxy)substituted calix[4]arenes (in cone and 1,3-alternate conformations). One of the conjugates was demetalated to give free porphyrin base derivative. The investigation of the fluorescence of the conjugates was studied in the presence of 18 metal perchlorates. The zinc porphyrinate derivatives were found to quench fluorescence in the presence of Cu(II), Al(III) and Cr(III) cations as well as on protonation. Metal-free conjugate was shown to act as a molecular probe for Zn(II), Cu(II) and Cd(II) cations due to strong and different changes of the emission caused by these metals.

The synthesis and characterization of a p-phenylene-bridged ZnPc dimer along with a preliminary study of this material as hole transporting material (HTM) in perovskite solar cells is described. The maximum efficiencies that obtained are 15.2% for ZnPc-p-ZnPc 1, thus demonstrating the potential of the Pc dimers that could pave the path to achieve highly efficient PSCs (PCE > 20%).

The first example of A2B2 tetrabenzoporphyrin (KW-4) was synthesized, characterized and evaluated as a sensitizer for dye-sensitized solar cells. UV-vis and fluorescence spectroscopy revealed red-shifted and broadened absorption spectra of A2B2 tetrabenzoporphyrin as compared with its A2 dibenzo- and A2B2 dibenzoporphyrin analogues, which is a desired feature of dyes for dye-sensitized solar cells. DFT calculations also indicate favorable electron density distribution on the HOMO and LUMO of KW-4. However, the power conversion efficiency of the solar cell based on tetrabenzoporphyrin KW-4 displayed inferior performance than that of the solar cell based on A2 dibenzoporphyrin KW-2. The lower performance of the KW-4 cell was ascribed to two factors: the low lying LUMO energy level leading to less efficient electron injection and the “flat geometry” of the dye on TiO₂ surface facilitating charge recombination and decreasing dye loading. The investigation of anchoring group effect suggests that the acrylic acid group is a better anchoring group than pentadienyl carboxylic acid.

In this study, two porphyrin chromophores metallated with ruthenium, RuTBP and RuTBPPy, were prepared and studied as sensitizers in dye-sensitized solar cells (DSSCs). The difference between the two dyes is the position (axial vs. peripheral) of the carboxylic anchoring group. This work examines the impact of this variation towards the optical, electrochemical and photovoltaic performance of DSSCs. The thorough photophysical and photovoltaic measurements indicated that the peripherally substituted sensitizer (RuTBP) presented higher photovoltaic performance compared to RuTBPPy. More specifically, DSSCs sensitized with RuTBP and RuTBPPy displayed an overall power conversion efficiency (PCE) of 5.12% and 4.08%, respectively. The higher PCE value of the DSSC sensitized with RuTBP is mainly attributed to the enhancement of J_sc and FF values. These factors were enhanced due to the efficient dye regeneration process, the suppression of back-charge recombination reactions and the longer electron lifetimes as evidenced from the electrochemical impedance spectra.

For energy storage applications, hexylsulfanyl-substituted CoPc and GO-CoPc electrodes were prepared on Ni foam, and then electrochemical properties of the materials were investigated. The GO-CoPc nanocomposite electrode exhibits 56 mFcm^-2 at 1,4 mAcm^-2 current density. The results show that the GO-CoPc nanocomposite electrode is a promising electroactive material for supercapacitors.

The direct insertion of carbon dioxide (CO₂) into three-membered rings, such as epoxides and aziridines, represents a relevant strategy to obtain cyclic carbonates and oxazolidinones, which are two useful classes of fine chemicals. The synthesis of these compounds can be efficiently catalyzed by a combination of metal porphyrin complexes and various co-catalysts in homogeneous systems. The catalytic efficiency of these systems is discussed herein by taking into account both the characteristics of the metals and the nature of the co-catalysts, either when used as two-component systems or when combined in bifunctional catalysts. Moreover, mechanistic proposals of the CO₂ cycloaddition processes are reported to provide a rationale of catalytic cycles in order to pave the way for designing more active and efficient catalytic procedures.

Microperoxidases 8 (MP8) and 11 (MP11) are heme-containing peptides obtained by the proteolytic digestion of Cytochrome c. They act as mini-enzymes that combine both peroxidase-like and Cytochrome P450-like activities that may be useful in the synthesis of fine chemicals or in the degradation of environmental pollutants. However, their use is limited by their instability in solution due to (i) the bleaching of the heme in the presence of an excess of H₂O₂, (ii) the decoordination of the distal histidine ligand of the iron under acidic conditions and, (iii) their tendency to aggregate in aqueous alkaline solutions, even at low concentrations. Additionally, both MP8 and MP11 show relatively low selectivity, due to the lack of control of the substrates by a specific catalytic pocket on the distal face of the heme. Both stability and selectivity issues can be effectively addressed by immobilization of microperoxidases in solid matrices, which can also lead to their possible recycling from the reaction medium. Considering their relatively small size, the pore inclusion of MPs into Metal-Organic Frameworks appeared to be more adequate compared to other immobilization methods that have been widely investigated for decades. The present minireview describes the catalytic activities of MP8 and MP11, their limitations, and various results describing their immobilization into MOFs which led to MP11- or MP8@MOF hybrid materials that display good activity in the oxidation of dyes and phenol derivatives, with remarkable recyclability due to the stabilization of the MPs inside the MOF cavities. An example of selective oxidation of dyes according to their charge by MP8@MOF hybrid materials is also highlighted.

In the last few years, the field of artificial hemoproteins has been expanding through two main strategies involving either the incorporation of synthetic metalloporphyrin derivatives into the chiral cavity of a protein or the directed evolution of natural hemoproteins such as myoglobin and cytochromes P450. First, various synthetic water-soluble porphyrins including ions of transition metals such as iron and manganese have been inserted covalently or by supramolecular anchoring into nonspecifically designed native proteins or into proteins modified by a minimum number of mutations. The obtained artificial hemoproteins were able to catalyze oxene transfer reactions such as epoxidation of alkenes or sulfoxidation of sulfides and cyclopropanation reactions with good activities and moderate enantioselectivities. Recently, a second approach, based on the design of the active site of already existing native hemoproteins such as myoglobin and cytochromes P450 by directed evolution, has led to new artificial hemoproteins that are able to catalyze oxene transfer reactions with improved activities as well as with abiological reactions. This approach thus provided promising tools for the catalysis of reactions such as intramolecular or intermolecular carbene and nitrene transfer reactions with high efficiencies. In addition, in all cases, after a few rounds of mutagenesis, mutants that were able to catalyze those reactions with a high enantioselectivity could be obtained. Finally, several groups showed that these new artificial metalloenzymes could also be used for the preparative scale-production of compounds with an excellent enantioselectivity, opening new pathways for the industrial synthesis of compounds of pharmaceutical interest.

Iron–porphyrins (i.e., hemes) are present throughout the biosphere and perform a wide range of functions, particularly those that involve complex multiple–electron redox processes. Some common heme enzymes involved in these processes include cytochrome P450, heme/copper oxidase or heme/non-heme diiron nitric oxide reductase. Consequently, the (hydr)oxo-bridged heme species have been studied for the important roles that they play in many life processes or for their application for catalysis and preparation of new functional materials. This review encompasses important synthetic, structural and reactivity aspects of the (hydr)oxo-bridged heme constructs that govern their function and application. The properties and reactivity of the bridging (hydr)oxo moieties are directly dictated by the coordination environment of the heme core, the nature and ligation of the second metal center attached to the (hydr)oxo group, the presence or absence of a linker, and the degree of flexibility around that linker within the scaffold. Here, we summarize the structural features of all known (hydr)oxo-bridged heme constructs and use those to categorize and thus, provide a more comprehensive picture of structure–function relationships.

This work describes the adsorption of synthesized cobalt mono (CoPc) and binuclear phthalocyanines (CoBiPc) with single walled carbon nanotubes (SWCNT) to form SWCNT-CoPc or SWCNT-CoBiPc as non-covalent conjugates onto glassy carbon electrodes (GCE). The cobalt complexes and their SWCNT-conjugate-modified electrodes were studied for their electrocatalytic oxidation towards 4-chlorophenol. All modified electrodes showed improved catalytic current and stability towards the detection of 4-chlorophenol. The best activity was observed for the SWCNT-CoBiPc2 system in terms of current response and the SWCNT-CoBiPc1 system in terms of resistance to electrode fouling.

A clam-shaped molecule comprising a Zn(II)-porphyrin and a Zn(II)-cyclam is synthesized and characterized. Its electrochemical behavior and catalytic activity for homogeneous electrochemical reduction of carbon dioxide (CO₂) are investigated by cyclic voltammetry and compared with those of Zn(II)-meso-tetraphenylporphyrin and Zn(II)-cyclam. Under N₂-saturated conditions, cyclic voltammetry of the featured complex has characteristics of its two constituents, but under CO₂-saturated conditions, the target compound exhibits significant current enhancement. Iterative reduction under electrochemical conditions indicated the target compound has improved stability relative to Zn(II)-cyclam. Controlled potential electrolysis demonstrates that, without addition of water, methane (CH₄) is the only detectable product with 1% Faradaic efficiency (FE). The formation of CH₄ is not observed under the catalysis of the Zn(II)-porphyrin benchmark compound, indicating that the CO₂-capturing function of the Zn(II)-cyclam unit contributes to the catalysis. Upon addition of 3% v/v water, the electrochemical reduction of CO₂ in the presence of the target compound gives carbon monoxide (CO) with 28% FE. Dominance of CO formation under these conditions suggests enhancement of proton-coupled reduction. Integrated action of these Zn(II)-porphyrin and Zn(II)-cyclam units offers a notable example of a molecular catalytic system where the cyclam ring captures and brings CO₂ into the proximity of the porphyrin catalysis center.

Iron(III) phthalocyaninate decorated with crown ether substituents, [(15C5)₄PcFe]Cl, efficiently catalyzed the insertion of carbene derived from ethyl diazoacetate to six amines functionalized with thiazole, thiazoline and thiadiazole heterocycles. The reactions were carried out under practical conditions using EDA:amine stoechiometric ratio with 0.05 mol% catalyst loading. Turnover numbers up to 3360 have been achieved. The aminoacid derivatives bearing heterocyclic moieties were obtained under catalytic conditions for the first time with 36–69% yields in the case of single N–H insertion products and up to 77% in the case of double N–H insertion products.

CoPc(COOH)₄-TiO₂ nanocomposites to be used as efficient visible light photocatalysts were obtained by modifying TiO₂ nanoparticles with cobalt(II) tetracarboxyphthalocyanine (CoPc(COOH)₄). The photocatalyst was then characterized by ultra-violet diffuse reflectance spectroscopy (UV-DRS), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The UV-DRS spectra showed that the absorbance spectrum of the modified catalyst was shifted to the visible region. Different textile dye solutions of Reactive Red 180, Acid Red 88 and Direct Orange 46 were efficiently degraded under visible light. Color removal rates were established to be 30%, 53% and 47% after 180 min for RR180, AR88 and DO46 dyes, respectively. The optimum catalyst concentration was determined to be 1 g/L of CoPc(COOH)₄-TiO₂. Development of the CoPc(COOH)₄-TiO₂ nanocomposite photocatalyst enabled the utilization of visible light irradiation for efficient photodegradation of organic textile dye solutions.

Alkyne-terminated Co phthalocyanine (CoPc) derivatives are linked to reduced graphene oxide nanosheets (GONS) via click chemistry and the conjugates are used for the electrocatalytic oxidation of 2-mercaptoethanol. CoPc derivatives where the alkyne group is separated from the Pc ring by an aliphatic and benzene ring (complex 3) showed the best catalytic activity (in terms of oxidation potential) in comparison to when only aliphatic chains were employed without the benzene ring (complex 2) and when there were no substituents (complex 1). The anodic oxidation of 2-mercaptoethanol on 3-GONS (linked) occurred at the least positive oxidation potential (-0.22 V vs. Ag|AgCl). 3-GONS (linked) was found to have the highest sensitivity with the lowest limit of detection of 0.08 μM. When the CoPc derivative and GONS were not linked but placed sequentially on the electrode, the electrocatalytic activity (in terms of LOD) was poorer than when linked. The electrodes modified with CoPc clicked to GONS are highly promising electrochemical sensors in terms of stability, sensitivity, good catalytic activity and ease of fabrication.

The intermediates operating in the cytochrome P450 catalytic cycle have been investigated for more than half a century, fascinating many enzymologists. Each intermediate has its unique role to carry out diverse oxidations. Natural time course of the catalytic cycle is quite fast, hence, not all of the reactive intermediates could be isolated during physiological catalysis. Different high-valent iron intermediates have been proposed as primary oxidants: the candidates are compound 0 (Cpd 0, [FeOOH]²⁺P450) and compound I (Cpd I, Fe(IV)=O por^•+P450). Among them, the role of Cpd I in hydroxylation is fairly well understood due the discovery of the peroxide shunt. This review endeavors to put the outstanding research efforts conducted to isolate and characterize the intermediates together. In addition to spectral features of each intermediate in the catalytic cycle, the oxidizing powers of Cpd 0 and Cpd I will be discussed along with most recent scientific findings.

Several families of herbicides, especially diphenyl ether (DPE) and pyrimidinedione, target the plant tetrapyrrole biosynthesis pathways and in particular one key enzyme, protoporphyrinogen IX oxidase (PPO). When plants are treated with DPE or pyrimidinedione, an accumulation of protoporphyrin IX, the first photosensitizer of this pathway, is observed in cytosol where it becomes very deleterious under light. Indeed these herbicides trigger plant death in two distinct ways: (i) inhibition of chlorophylls and heme syntheses and (ii) a huge accumulation of protoporphyrin IX in cytosol. Recently, a strategy based on plant transgenesis that induces deregulation of the tetrapyrrole pathway by up- or down-regulation of genes encoding enzymes, such as glutamyl-tRNA reductase, porphobilinogen deaminase and PPO, has been developed. Against all expectations, only transgenic crops overexpressing PPO showed resistance to DPE and pyrimidinedione. This herbicide resistance of transgenic crops leads to the hypothesis that the overall consumption of herbicides will be reduced as previously reported for glyphosate-resistant transgenic crops. In this review, after a rapid presentation of plant tetrapyrrole biosynthesis, we show how only PPO enzyme can be the target of DPE and how transgenic crops can be further resistant not only to herbicide but also to abiotic stress such as drought or chilling. Keeping in mind that this approach is mostly prohibited in Europe, we attempt to discuss it to interest the scientific community, from plant physiologists to chemists, who work on the interface of photosensitizer optimization and agriculture.

In the present review, examples are provided illustrating the application of resonance Raman microscopy to heme protein single crystals to highlight the artifacts induced by the crystallization process or the conformational alteration induced by cooling. Moreover, the structural information determined from the RR spectra of heme proteins in solution and crystals is compared to that obtained from their X-ray structures to show how the combined spectroscopic/crystallographic approach is a powerful weapon in the structural biologist’s armamentarium.

The degradation of the green pigment chlorophyll in plants is known to yield phyllobilins as highly abundant linear tetrapyrroles. Recently, a split path of the degradation pathway has been discovered, leading to so-called dioxobilin-type (or type-II) phyllobilins. The first characterized type-II phyllobilin was colorless featuring four deconjugated pyrrole units. Similar to the type-I branch, for which yellow oxidation products of the colorless phyllobilins — the type-I phylloxanthobilins — are known, a type-II phylloxanthobilin has recently been characterized from senescent leaves of grapevine. Type-I phylloxanthobilins appear to be actively produced in the plant, are known to possess interesting chemical properties, and were shown to act as potent antioxidants that can protect cells from oxidative stress. Here we report the isolation and structural characterization of a type-II phylloxanthobilin from de-greened leaves of savoy cabbage, which turned out to be structurally closely related to bilirubin. Bilirubin is known to possess high antioxidative activity; in addition, savoy cabbage is considered to promote health benefits due to its high content in antioxidants. We therefore investigated the in vitro antioxidative potential of the newly identified type-II phylloxanthobilin using two different approaches, both of which revealed an even higher antioxidative activity for the type-II phylloxanthobilin from savoy cabbage compared to bilirubin.

The sensor kinases MsmS and RdmS from the methanogenic archaeon Methanosarcina acetivorans are multidomain proteins containing a covalently linked heme cofactor. This cofactor is connected via a single cysteine residue in a GAF domain. Although both proteins were shown to display a redox-dependent control of the downstream kinase module, this property appears to be independent of the heme cofactor. We therefore envision an additional sensor role for the heme cofactor. In order to learn more about the heme binding pocket and its constitution, UV-vis spectroscopy in combination with site-directed mutagenesis was performed on the isolated heme-binding sGAF2 domain and the full-length protein. The data indicate a 6-coordinated heme with a proximal histidine ligand and a smaller ligand, likely a water molecule on the distal site. The latter is also thought to be the sensory site and is shown to easily undergo ligand exchange.

The axial coordination properties of six zinc tetraarylporphyrins with seven different nitrogenous bases were examined in CH₂Cl₂ for derivatives containing four β,β′-fused butano or benzo groups and the equilibrium constants (logK) determined using spectral titration methods. The examined compounds are represented as butano(YPh)₄PorZn and benzo(YPh)₄PorZn, where Por is the porphyrin dianion and Y is a CH₃, H or Cl substituent on the para-position of each meso-phenyl ring of the macrocycle. The initial four-coordinate butano- and benzoporphyrins will axially bind one nitrogenous base to form five-coordinate derivatives in CH₂Cl₂ and this leads to a 4–22 nm red-shift of the Soret and Q bands. The logK values range from 1.98 to 4.69 for butano(YPh)₄PorZn and from 3.42 to 5.36 for benzo(YPh)₄PorZn, with the exact value depending upon the meso and β-substituents of the porphyrin and the conjugate acid dissociation constants (pK_a) of the nitrogenous base.

Five meso-tetraaryl open-chain pentapyrroles were synthesized and characterized as to their electrochemistry and protonation reactions in nonaqueous media. The investigated compounds are represented as (Ar)₄PPyH₃ where Ar = m,m-F₂Ph, p-BrPh, Ph, m,p,m-(OMe)₃Ph or p-MePh and were characterized by UV-vis and ¹H NMR spectroscopy, mass spectrometry and electrochemistry. Cyclic voltammetry was used to measure redox potentials, while protonation involving the conversion of (Ar)₄PPyH₃ to [(Ar)₄PPyH₅]²⁺ was monitored by UV-vis absorption spectroscopy. Equilibrium constants for proton addition were calculated using the Hill equation. One of the pentapyrroles was also structurally characterized. The electrochemical data, protonation constants and crystal structure were then compared with data for previously examined pentapyrroles and analyzed as a function of the solvent properties and nature of substituents on the meso-phenyl rings of the macrocycle.

The process of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin electropolymerization has been studied by the quartz crystal microbalance method in different electrodeposition conditions. The films were deposited in two modes: in potentiostatic conditions (at the potential of +2 V) and in potentiodynamic conditions (CV with the potential scan rate of 20 mV/s). The effect of electrolysis parameters on 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin electropolymerization has been studied by obtaining films in two modes and using two supporting electrolytes: tetrabutylammonium perchlorate or tetrabutylammonium hexafluorophosphate. The biggest film mass gain was observed on a clean electrode surface. At further film deposition on the polyporphyrin-coated electrode, the film mass growth stopped. The electrodeposition effectiveness was somewhat higher in the potentiodynamic conditions, with the formation of a looser film. The nature of the supporting electrolyte did not have a significant effect on the electrodeposition process. A significant contribution to the deposition was made by the electrode material. The film thickness was 25–80 nm. The films possessed p-type conductivity; and the flat-band potential for poly-H₂T(4-OHPh)P obtained in potentiodynamic conditions was 0.33 V, for poly-H₂T(4-OHPh)P obtained in potentiostatic conditions it was ‑0.16 V.

The following section is included:

• Cumulative Index