Journal of Porphyrins and Phthalocyanines

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 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.

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.

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.

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 $\beta$-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.

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.

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.

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 $\mu$M. 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.

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 × 10${}^{11}$ s${}^{-1}$ vs. 1.0 × 10${}^{11}$ 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.

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 ${}^{13}$C 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.

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 $J_{\mathrm{\text{sc}}}$ 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.

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.

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.

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$deg$ and 18$deg$. ThPc and DThPc exhibit red-shifted and broadened absorption because of the extension of $\pi$ conjugations through porphycene to the substituted thiophenes. We found that introduction of thiophene units onto porphycene results in decreasing the HOMO–LUMO differences effectively.

This study, subphthalocyanines (SubPc) and SubPc integrated TiO₂ nanoparticles (SubPc-TiO${}_2)$ were synthesized as novel photosensitizers. Their PDT effects were evaluated. Furthermore, nuclear imaging potential of ${}^{131}$I-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 ${}^{131}$I radionuclide (${}^{131}$I-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 ${}^{131}$I (${}^{131}$I-SubPc-TiO${}_2)$ 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. ${}^{131}$I-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.

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.

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.

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, ${}^{13}$C NMR, FT-IR, UV-vis and MS spectral data. The molecular geometry and gauge including atomic orbital (GIAO) ¹H and ${}^{13}$C 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 (${\mathrm{\Phi }}_{\mathrm{\Delta }})$ 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.