Journal of Porphyrins and Phthalocyanines

In this review I summarize our attempts to prepare supramolecular assemblies from phthalocyanine dyes, the objective being to design functional materials that have specific properties, $e.g.$ electron conduction. We explore several supramolecular methods to achieve phthalocyanine assembly, $e.g.$ by attaching crown ethers to the phthalocyanine rings and combining these with alkali metal ions, by providing them with long aliphatic tails, and by using aided assembly techniques such as wetting-dewetting interactions on surfaces. Also, chirality has been applied as a tool to produce new self-assembled structures. In our studies we focus on the electron conducting properties of the molecular materials and on their use as alignment layers for the fabrication of liquid-crystal displays.

Creation of novel $\pi$-conjugated molecules is an important research topic. I describe in this account an approach to this aim that is based on the use of the distorted conformation of porphyrins. Planarization of distorted molecules enables the synthesis of heteroatom-containing porphyrin derivatives. Furthermore, dearomatization reaction proves effective to construct distorted conformations from planar $\pi$-conjugated molecules under mild reaction conditions. According to this protocol, we have succeeded in the synthesis of heteroatom-containing curved-$\pi$ conjugated molecules that had never been achieved by conventional protocols. In particular, a nitrogen-embedded buckybowl is the first example of a buckybowl having a heteroatom in its central position, which exhibits unique properties due to the incorporation of the heteroatom in its curved $\pi$-surface.

Porphyrins and phthalocyanines feature strong light absorption, capacity for metal chelation, and a track record of use in human therapeutic applications. Various conjugates and formulations of these macrocycles have shown potential to forge new applications in the biomedical sciences. Our lab has explored several such approaches including porphyrin polymer hydrogels, porphyrin-lipid nanovesicles, and surfactant-stripped micelles. These all feature in common a high density of tetrapyrroles, as well as unique functional properties. Porphyrin polymer hydrogels with high porphyrin density and bright fluorescence emission were demonstrated for use as a new class of implantable biosensors. Porphyrin-lipid nanovesicles hold potential for phototherapy, imaging, and also drug and vaccine delivery. Surfactant-stripped micelles have been developed for high-contrast photoacoustic imaging. In this ICPP Young Investigator Award brief perspective, we discuss our own efforts on these fronts. Taken together, the results show that tetrapyrroles enable new approaches for tackling biomedical problems and also confirm what was already well-known to members of the Society of Porphyrins and Phthalocyanines: that these molecules are remarkably versatile and enable research to flow in unexpected directions.

Understanding aromaticity is crucial for predicting the molecular properties and reactivity of cyclic $\pi$-conjugated systems. In this review, representative reports on the evaluation of aromaticity via spectroscopic methods in various expanded porphyrin systems are presented. The relationship between the photophysical properties and distinct aromatic characteristics in Hückel aromatic compounds was revealed through notable spectroscopic features exhibited by aromatic expanded porphyrins. Furthermore, modulating the molecular conformation and chemical environment enabled us to distinguish unique Möbius aromatic molecules successfully. These findings provide insight into the elemental molecular properties and aromaticity in expanded porphyrin systems and their potential real-world applications.

This manuscript highlights the author’s contributions to phthalocyanine chemistry, especially the applications based on their electrochemistry and photophysicochemistry. In particular, the use of phthalocyanines as electrocatalysts and photocatalysts is presented. For photocatalysis, photodynamic antimicrobial chemotherapy and pollution control using green technologies are highlighted. For electrocatalysis the phthalocyanines are employed for the detection of pollutants and environmentally important molecules. Phthalocyanines are combined with nanomaterials for improved photocatalysis and electrocatalysis.

Photodynamic therapy is a photochemistry-based approach, approved for the treatment of several malignant and non-malignant pathologies. It relies on the use of a non-toxic, light activatable chemical, photosensitizer, which preferentially accumulates in tissues/cells and, upon irradiation with the appropriate wavelength of light, confers cytotoxicity by generation of reactive molecular species. The preferential accumulation however is not universal and, depending on the anatomical site, the ratio of tumor to normal tissue may be reversed in favor of normal tissue. Under such circumstances, control of the volume of light illumination provides a second handle of selectivity. Singlet oxygen is the putative favorite reactive molecular species although other entities such as nitric oxide have been credibly implicated. Typically, most photosensitizers in current clinical use have a finite quantum yield of fluorescence which is exploited for surgery guidance and can also be incorporated for monitoring and treatment design. In addition, the photodynamic process alters the cellular, stromal, and/or vascular microenvironment transiently in a process termed photodynamic priming, making it more receptive to subsequent additional therapies including chemo- and immunotherapy. Thus, photodynamic priming may be considered as an enabling technology for the more commonly used frontline treatments. Recently, there has been an increase in the exploitation of the theranostic potential of photodynamic therapy in different preclinical and clinical settings with the use of new photosensitizer formulations and combinatorial therapeutic options. The emergence of nanomedicine has further added to the repertoire of photodynamic therapy’s potential and the convergence and co-evolution of these two exciting tools is expected to push the barriers of smart therapies, where such optical approaches might have a special niche. This review provides a perspective on current status of photodynamic therapy in anti-cancer and anti-microbial therapies and it suggests how evolving technologies combined with photochemically-initiated molecular processes may be exploited to become co-conspirators in optimization of treatment outcomes. We also project, at least for the short term, the direction that this modality may be taking in the near future.

A series of first-row transition metal complexes of tetrakis(pentafluorophenyl)porphyrin (1), denoted as 1-M (M $=$ Mn, Fe, Co, Ni, Cu, and Zn), were synthesized and examined as electrocatalysts for the hydrogen evolution reaction (HER). All these transition metal porphyrins were shown to be active for HER in acetonitrile using trifluoroacetic acid (TFA) as the proton source. The molecular nature and the stability of these metal porphyrins when functioning as HER catalysts were confirmed, and all catalysts gave Faradaic efficiency of >97% for H₂ generation during bulk electrolysis. Importantly, by using 1-Cu, a remarkably high turnover frequency (TOF) of 48500 s${}^{-1}$ 1-Cu the most efficient among this series of metal porphyrin catalysts. This TOF value also represents one of the highest values reported in the literature. In addition, electrochemical analysis demonstrated that catalytic HER mechanisms with these 1-M complexes are different. These results show that with the same porphyrin ligand, the change of metal ions will have significant impact on both catalytic efficiency and mechanism. This work for the first time provides direct comparison of electrocatalytic HER features of transition metal complexes of tetrakis(pentafluorophenyl)porphyrin under identical conditions, and will be valuable for future design and development of more efficient HER electrocatalysts of this series.

Conjugated porphyrin dimers have captured the imagination of scientists due to a set of unique spectroscopic features such as remarkable nonlinear-optical properties, high yields of singlet oxygen sensitization and the absorption and emission in the far-red region of the visible spectrum. Here we review a range of newly emerged applications of porphyrin dimers as sensors of their microenvironment such as viscosity and temperature. We discuss the sensing mechanism based on the known conformational flexibility of the dimer structure and describe possible applications of these unique sensors, from detecting viscosity increase during photoinduced cell death to structural responses of polymers and artificial lipid membranes, to temperature changes, and to mechanical deformation.

Doxorubicin (DOX) resistance, which results in a reduced accumulation of DOX in the nucleus and hence decreased DNA damage, is a major challenge for chemotherapy against hepatocellular carcinoma. In this paper, we combined chemotherapy with photodynamic therapy (PDT) to combat DOX-resistant human hepatocellular carcinoma cells. We have prepared the polymeric micelles conjugating with DOX and zinc(II) phthalocyanine (ZnPc) through a pH-responsive hydrazone linker and a glutathione (GSH)-responsive disulfide linker, respectively. The polymeric micelles (DOX-ZnPc-micelles) exhibited a spherical shape with a size of about 98 nm diameter and showed excellent stability in aqueous solution. Due to the self-quenching of the ZnPc inside the micelles, DOX-ZnPc-micelles did not emit fluorescence upon red light irradiation. Drug release experiments verified that DOX and ZnPc could be released under acidic conditions and reducing environments, respectively. A higher concentration of DOX was internalized into DOX-resistant R-HepG2 cells through the delivery of polymeric micelles when compared with the free DOX, hence DOX-ZnPc-micelles exhibited a significant enhancement in anticancer activity. The IC${}_{50}$ value of DOX against R-HepG2 cells was found to be 21 $\mu$M when combined with PDT and it was 5-fold less than that of a single treatment of DOX (102 $\mu$M). The DOX-ZnPc-micelles could induce cell apoptosis and necrosis on R-HepG2 cells by combined therapeutic modalities, while these micelles induced only apoptosis on HepG2 cells. We have demonstrated that utilization of polymeric micelles can significantly enhance the cellular uptake and cytotoxicity of DOX against R-HepG2 cells when compared with free DOX. Moreover, PDT can act as an adjuvant therapeutic modality and combine with chemotherapy to further improve therapeutic efficacy. Overall speaking, DOX-ZnPc-micelles can overcome DOX resistance and induce a synergistic therapeutic effect against DOX-resistant R-HepG2 cells, hence improving the therapeutic efficacy when compared with monotherapy.