Journal of Porphyrins and Phthalocyanines

The application of modern synthetic methods to the unsymmetrical functionalization of phthalocyanines has allowed in the last years the preparation of a plethora of phthalocyanine-based molecules, some of which have found remarkable application in different fields of materials science such as nonlinear optics and photovoltaics. In particular, transition metal (especially, palladium) mediated reactions have been crucial tools in the synthesis of quite sophisticated derivatives containing π-conjugated units. The main problem that synthetic chemists working in this field had to overcome was the strong tendency of these macrocycles toward aggregation, which can preclude the preparation of some unsymmetrically substituted Pcs. This micro-review gives a brief overview of the most relevant synthetic methods developed in Spain and Portugal that have been applied to the efficient preparation of Pc-based systems for different applications.

Porphyrins and other pyrrolic macrocycles can participate in a range of pericyclic reactions. This review deals mainly with their use in Diels-Alder reactions (as dienes and dienophiles) and in 1,3-dipolar cycloadditions (as 1,3-dipoles and dipolarophiles)

With reference to the Portugal-Spain Special Issue of the Journal of Porphyrins and Phthalocyanines, this highlight is mainly concerned with the contribution by the University of Aveiro group on the functionalization of the β-pyrrolic positions of triarylcorroles via cycloaddition reactions.

Here, we report the progress in the chemistry of porphyrin-phthalocyanine and phthalocyanine-phthalocyanie multinuclear systems being developed by the organic chemistry groups of Cavaleiro and Torres.

Improvements over the Rothemund classical reaction methods have allowed the development of capacity to obtain a wide range of structures that were earlier unavailable. Performing the reaction in a mixed nitrobenzene/carboxylic acid medium allowed improvements of yield and purity of the porphyrin obtained, and in some cases the control of the oxidation level of the macrocycle. More recently, novel microwave synthetic methodologies were exploited to achieve important improvements in simple porphyrin chemistry. Tidy sulphonations of simple porphyrins opened the way to diverse desired, inexpensive structures in a very simple manner. The option to concentrate interests on improvements of synthetic methods to obtain simple and diversified tetrapyrrolic structures proved to be advantageous. Interesting biomimetic oxidation and photooxidation systems and PDT sensitizers were developed and significant knowledge was achieved in these specific and related areas. This review presents a view of our own results in the synthetic area, and outlines the contributions therefrom to the study of biomimetic and therapeutic processes.

Subphthalocyanines, lower homologs of phthalocyanines, show great promise for applications in many fields of contemporary research such as non-linear optics, donor-acceptor systems for photovoltaics, photodynamic therapy and anion sensing. This short review gives a brief overview of the latest developments in the chemistry, characterization, self-organization, properties and applications of this fascinating molecule.

This highlight gives a brief summary of recent developments in the chemistry of hemiporphyrazines in the Iberian Peninsula, with a focus on triazolehemiporphyrazines. Among all porphyrinoids, hemiporphyrazines offer the advantage of exhibiting intrinsic D_2h symmetry and this feature has been exploited in the design of materials endowed with a variety of properties such as liquid crystalline behavior, electric and magnetic features and nonlinear optical performance, among others.

The formation and structure of the title aggregates are paradigms of the self-assembly of amphiphilic molecular building blocks in supramolecular chemistry. This review summarizes the research in the University of Barcelona on the homoassociation of the water soluble meso 4-sulfonatophenyl-and phenyl substituted porphyrins.

Phthalocyanines are an interesting class of aromatic macrocycles which possess exciting electrical, redox and photophysical properties that make them ideal building blocks for applications in different technological fields. However, the incorporation of phthalocyanines into devices is often tied to the possibility of organizing these macrocycles into arrays using supramolecular interactions. To date, several supramolecular motifs such as hydrogen-bonding, donor-acceptor or metal-ligand interactions have been used to promote the phthalocyanines' organization in solution. Furthermore, such weak, non-covalent interactions have also been widely employed to foster the organization of these macrocycles in condensed phases such as liquid-crystals or thin films. This micro-review provides a brief overview of the contribution made by some research groups in Spain towards the preparation of organized phthalocyanine-based supramolecular systems.

During the last ten years, our research group has been applying metal-mediated self-assembly processes to the construction of multiporphyrin functional assemblies. The construction of well-defined and discrete supramolecular structures resulting from self-assembly requires the use of multiple and separated connections operating in one or more closed loops. Consequently, the great majority of the multiporphyrin assemblies that we have prepared are of cyclic nature. We have placed special emphasis not only on the characterization in solution of the formed assemblies but also on the thermodynamic characterization of the assembly process and in the assessment of cooperativity. Finally, we also present examples in which functionality has been derived from the three-dimensional structures of multicomponent assemblies.

A theoretical study was carried out on both porphyrin-based conjugates (with interest in the so-called artificial photosynthesis) and subphthalocyanine aggregates (with potential applications as new materials for optoelectronics, solar energy and other uses). A simple molecular orbital model for studying the role of the spacer groups in the electron transfer in porphyrin-quinone conjugates was developed. The influence of the π-π interaction, hydrogen association and covalent linkage on the stability and structural features in porphyrin-porphyrin complexes as well as the charge separation in donor-acceptor porphyrin dimers, were reproduced. Theoretical models suggest the potential feasibility of SubPc's aggregative processes leading to nanometer-sized fully aromatic fullerene-like molecular architectures.

Studies of excited singlet and triplet states of porphyrins and phthalocyanines in organized media of reverse micelles, vesicles, monolayers, and Langmuir-Blodgett films along with more complex supramolecular organizates with proteins and dendrimers, are reported. Self-assembly in these systems was followed by imaging and temporal fluorescence techniques.

An overview of the use of electrospray mass spectrometry for the study of non-covalent interactions of cationic porphyrins and small DNA duplexes, highlighting the work developed in the Mass Spectrometry Laboratory of the University of Aveiro, is presented here.

meso-tetraarylporphyrins with different substituents linked either to an aryl ring or to a β-pyrrolic position were studied by Electrospray (ESI) Tandem Mass Spectrometry (MS/MS). The electrospray mass spectra (ESI-MS) of meso-tetraarylporphyrins show the molecular ions and no significant fragmentation is noted. Structural information can be obtained by inducing fragmentation of the ions generated under ESI conditions. The product ions formed and registered in the tandem mass spectra (ESI-MS/MS) are characteristic of the chemical structure of the groups linked to the porphyrin and depend on their location. Also, the same functional group linked either to the aryl ring or to the β-pyrrolic position yields different product ions that confirm their position. Taking into consideration the Portugal-Spain special issue of the Journal of Porphyrins and Phthalocyanines, in this highlight we analyze the work done at the University of Aveiro related to the use of mass spectrometry in the structural characterization of meso-tetraarylporphyrins with carbohydrate, nitro and amino acid groups.

Photodynamic therapy (PDT) is a rapidly expanding alternative to the treatment of solid tumors and other highly-proliferative diseases due to its many attractive features: high selectivity, repeatability, and lack of serious adverse effects. The five drugs approved for use in PDT to date suffer from different problems that limit their efficacy and safety. Current understanding of cell death mechanisms offers an opportunity for the development of new, more efficient and safer drugs. This highlight describes the efforts of our research group in the PDT field: chemical development of porphycenes as PDT photosensitizers, photophysical screening of new families of potential PDT agents, and development of spectroscopic techniques for directly monitoring singlet oxygen and thus better understand the production, diffusion, and reactivity of this primary cytotoxic species in cells.

Photodynamic therapy is an emerging modality of cancer treatment based on the use of photosensitizing drugs, which accumulate selectively in tumor cells. Exposure to visible light induces local cytotoxic effects that lead selectively to tumor cell death in the irradiated region, thereby minimizing the risk and extension of unwanted secondary effects. One of the goals sought in the development of photodynamic therapy drugs is the selective targeting of tumor cells. As a general trend, the indiscriminate delivery of drugs is being increasingly substituted by the selective delivery to pathological tissues which can be achieved by embedding them into transporters that actively recognize differential factors of tumor cells and tissues as compared to healthy ones. Likewise, the chemical modification of the photosensitizers is a valid strategy to change the subcellular localization of the drug. The use of liposomes as transporters for targeted delivery of drugs has attracted particular attention during the last two decades. After a period characterized by the skepticism expressed by certain scientists in the field of drug delivery, interest in liposomes was rejuvenated by the introduction of fresh ideas from membrane biophysics.

Photodynamic therapy (PDT) is a subject of increasing biomedical research and represents a very promising therapeutic modality for palliative or even curative treatment of some superficial or endoscopically accessible tumors. In addition to the first photosensitizers (PSs) applied (hematoporphyrin-based drugs), second generation PSs with improved photophysical and photobiological properties are now studied using cell cultures, experimental tumors and clinical trials. On the other hand, there is a growing interest in the analysis of cell death mechanisms by apoptosis, which is especially relevant in oncology, because many anticancer drugs work, at least in part, by triggering apoptosis in neoplastic cells both in vitro and in vivo. The evaluation of cell death mechanisms is an important parameter to determine the efficacy and the potential toxicity of a treatment, allowing better adjustment of protocol. Using cell cultures, our research team has studied the mechanisms of cell damage and death implicated in the photodynamic processes, as well as the relationship between the cellular localization of the PS and the organelle damage during photosensitization. The results obtained in our laboratory provide a deeper understanding on the action mechanisms that lead to cell inactivation by PDT, and also allow selection of PSs with higher potential for clinical application than those currently in use.

Tumor cell death induced by photodynamic therapy (PDT) with different photosensitizers (PSs) is due to the selective damage of several membranous organelles including mitochondria, lysosomes and Golgi apparatus. Other cell structures such as the cytoskeleton (CSK) (microtubules, actin microfilaments and cytokeratin intermediate filaments) and the cell adhesion components (cadherins and integrins) are also implicated in cell death induced by PSs. CSK and adhesion components are responsible for many cellular functions such as the maintenance of morphology, motility, division and adhesion, all of them of fundamental importance for growth and dissemination of tumors. Therefore, they are considered very important targets for anticancer therapies, including PDT. In addition, similarly to the rest of the anticancer therapies, PDT often leaves a significant number of surviving tumor cells. The reorganization of CSK as well as the adhesion proteins in the PDT resistant cells affect their invasive migratory capabilities. Taking into account all these features, both CSK and adhesion proteins are crucial targets of PDT.

Photodynamic therapy (PDT) of cancer is based on the cytotoxicity induced by a photosensitizer (PS) in the presence of oxygen and visible light, with formation of reactive oxygen species which cause cell death and tumor destruction. This work describes the response of the murine mammary adenocarcinoma, LM3, to repeated PDT using meso-tetrakis(4-N,N,N-trimethylanilinium)porphine (TMAP), a PS that has been overlooked for PDT applications. Intradermal LM3 tumors in BALB/c mice (controls) were left untreated, only treated with light, only injected with 0.9% NaCl solution or with TMAP alone (10 μg/0.1 ml). For PDT, the intratumoral PS injection was followed 1 h later by blue-red light irradiation (290 J.cm^-2). In all cases, control and PDT treatments were performed on the depilated and glycerol-covered skin which covers the tumor of anesthetized animals, and repeated 4 times (every 2 days). No significant differences were found in the growth rate of all control tumors. PDT-treated tumors showed complete and long-term regression in 4 out of 5 mice, and cure in one animal. The survival of PDT-mice was significantly longer than that of controls (TMAP alone), showing a lower number of tumor-draining lymph node metastasis. The PDT protocol applied in the present work (intratumoral PS injection, repeated photosensitizing treatments, and reduction of tissue light scattering by glycerol) could be a useful strategy in studies on PDT of cancer.

Photodynamic therapy (PDT) is a promising treatment for several types of cancers. It involves the synergetic effect of light, oxygen and an appropriate photosensitizer. Extensive studies on the synthetic modulation of the structure of tetrapyrrolic macrocycles allowed for the optimization of chemical and physical properties of such photosensitizers. The progress from porphyrins to chlorins and more recently to bacteriochlorins clearly shows the improvements achieved in PDT photosensitizers. This paper summarizes our recent contribution to the synthesis of stable amphiphilic halogenated meso-tetraarylbacteriochlorins. Their photophysics, in vitro cytotoxicity and phototoxicity are presented and their potential use as photosensitizer for PDT application is assessed.

In this highlight an overview of the advances performed by the Aveiro group on the design and synthesis of tetrapyrrolic photosensitizers with potential photodynamic antimicrobial activity is presented.

The viral safety of blood derived products relies in properly chosen inactivation procedures. In this way, it has been reported that some photosensitizers are useful products for blood sterilization. The data presented here show the high incorporation efficiency of the chlorin 3-phorbinepropanol, 9,14-diethyl-4,8,13,18-tetramethyl-20-(3S-trans) (CHL) into anionic unilamellar liposomes, give a protocol for the steric immobilization of chlorin-containing liposomes in a chromatographic support and provide the studies of photodynamic inactivation of bovine viral diarrhea virus (BVDV) and encephalomyocarditis virus (EMCV) with chlorin-containing liposomes, free in solution and immobilized on Sephacryl S-1000 beads. The study demonstrates the successful inactivation of the enveloped virus BVDV by both preparations in culture medium and the resistance of the non-enveloped virus EMCV. The effectiveness of CHL-containing liposomes, in solution and immobilized in the chromatographic support, decreased when the culture media was replaced with human blood plasma. Moreover, the reduction factor of the virus titer after irradiation was smallest when immobilized liposomes were used. Nevertheless, the reduction factor for the virus titers of enveloped viruses after irradiation of human blood plasma samples with immobilized chlorin-containing liposomes increased with the reduction of the sample thickness. The more outstanding aspect of this paper is the design of a system useful for blood sterilization that can be easily removed after photodynamic treatment and, therefore, able to be applied in the manufacturing processes.

Cheap and abundant natural products can be transformed into products of higher commercial value. One of the approaches for the functionalization of organic compounds is their oxidation in the presence of an oxygen atom donor, under the influence of a suitable catalyst. Metalloporphyrins, with structures based on the well known meso-tetraphenylporphyrin (TPPH₂), are amongst the catalysts commonly studied and have demonstrated to be efficient in the oxygenation of organic compounds. These transformations have been studied in the presence of different oxygen atom donors. However, our biomimetic oxidative approach is based on the use of clean and environmentally benign hydrogen peroxide in the presence of metalloporphyrins. This approach will be outlined in this review.

Mixed films containing ionic water-soluble or -insoluble porphyrins and amphiphilic anchors have been prepared at the air/water interface and on solid support (Langmuir-Blodgett, LB). Their molecular organization has been controlled by different strategies. Monomer, twisted dimer and slipped dimers, and tetramer patterns have been organized at those interfaces as a function of the central metal ion of water-soluble porphyrins, the lipid host-matrix and the applied surface pressure. In addition, stable monomolecular or tri-layers are possible to fabricate. Moreover, for water-insoluble porphyrins, dilution by increasing molar ratio of the amphiphilic matrix in mixed films facilitates the disaggregation, i.e. the monomer porphyrin moieties increases. As a result, the response to the presence of the toxic gas, i.e. the speed of the response and recovery phases, the temperature and concentration ranges has been notably enhanced.

The group of the University of Valladolid is a multidisciplinary team formed by chemists, physicists and engineers. The activities of the group are focused to the study of the physicochemical properties of nanostructured Langmuir-Blodgett thin films based on phthalocyanines and their applications. Films of a variety of phthalocyanine molecules including several metallophthalocyanines, lanthanide double decker phthalocyanines and heteroleptic derivatives have been prepared. Their spectroelectrochemical properties have been described in detail and compared with those observed in disordered casted films or microcrystalline evaporated films. The group has dedicated special attention to films based on rare earth double decker compounds due to their unique semiconducting, optical and electrochemical properties. A rich electrochromism has been demonstrated in thin films of this family of compounds. The reversibility is improved in nanostructured Langmuir-Blodgett films. This has permitted development of an electrochromic display that can change its color from blue to green and finally to red. At the present moment, our main objective is the design of sensors able to detect gases and liquids. It has been demonstrated that thin film assemblies based on rare earth bisphthalocyanines modify their conductivity and their optical properties in the presence of electron donor or electron acceptors gases. Changes are also observed when the devices are exposed to Volatile Organic Compounds such as esters, alcohols or aldehydes which are responsible of odors in foods and beverages. Liquid sensors have also been developed. Their working principle is based in the fact that the rich electrochemical properties of phthalocyanine thin films are extremely sensitive to the nature of the electrolytic solution. Arrays of phthalocyanines have been used to construct an electronic nose able to discriminate odors from a variety of foods and beverages. Similarly, phthalocyanines have also been used to construct an electronic tongue based on voltammetric sensors. This is one of the main contributions of the group to the field of sensors.

This paper presents the research that is currently undergoing in our group toward the development of optical sensing layers based on iron(II) phthalocyanine complexes immobilized on nanostructured solid supports. Several FePc-N donor ligands have been prepared and coated into different nanostructured metal oxides. Optical properties, chemical variables, analytical features, selectivity rates, response times and type of nanostructure supports have been evaluated; in some cases, interesting correlations between them have been deduced. In addition, thermostability studies have been carried out, providing access to a second generation of nanostructured metal oxides.

The importance and complexity of energy and electron transfer reactions in biological and artificial light energy conversion systems have prompted the preparation and photophysical study of donor-acceptor (D-A) molecular models. This article aims to highlight the efforts of Portuguese and Spanish research groups on the design, synthesis and photophysical study of molecular and supramolecular donor-acceptor systems based on phthalocyanines, subphthalocyanines and porphyrins.

This paper presents the work developed in Spain, in collaboration with other European groups, on the synthesis and photovoltaic applications of hybrid systems comprised of single-walled nanotubes linked to either phthalocyanine or porphyrin moieties.

Phthalocyanines, porphyrins and analogs are highly versatile and stable molecules with an extended π-aromatic system and high extinction coefficients, making them suitable for integration in solar cells as photoactive components and/or as light-harvesting materials. The most significant results by Spanish groups in the field are collected in this report.

This paper aims to review the advances achieved in the field of nonlinear optics in relation to phthalocyanines and other related compounds. The main focus is on electronic nonlinear processes, such as second- and third-harmonic generation, and mostly on the work performed by Portuguese and Spanish research groups. Several aspects in which these teams were pioneers are described in more detail. In particular, they performed numerous experiments in solution, thanks to their synthetic efforts in preparing soluble compounds, thus enabling the determination of the nonlinear parameters at a molecular level. They also measured for the first time the real and imaginary components (i.e. the magnitude and the phase) of the nonlinear parameters of phthalocyanines and, in some cases, their frequency dispersion behavior. Such detailed studies allow for the elaboration of microscopic models to identify the electronic levels involved in nonlinear processes. Some Spanish groups were also pioneers in the characterization of the nonlinear optical properties of unsymmetrically substituted phthalocyanines and other related compounds, such as triazolehemiporphyrazines and subphthalocyanines.