Journal of Porphyrins and Phthalocyanines

Photosynthetic organisms provide, directly or indirectly, the energy that sustains life on earth by harvesting light from the sun. The amount of light impinging on the surface of the earth vastly surpasses the energy needs of life including man. Harvesting the sun is, therefore, an option for a sustainable energy source: directly by improving biomass production, indirectly by coupling it to the production of hydrogen for fuel or, conceptually, by using photosynthetic strategies for technological solutions based on non-biological or hybrid materials. In this review, we summarize the various light climates on earth, the primary reactions responsible for light harvesting and transduction to chemical energy in photosynthesis, and the mechanisms of competitively adapting the photosynthetic apparatus to the ever-changing light conditions. The focus is on oxygenic photosynthesis, its adaptation to the various light-climates by specialized pigments and on the extension of its limits by the evolution of red-shifted chlorophylls. The implications for potential technical solutions are briefly discussed.

According to recent advances in nanotechnology, various nano-sized formulations have been designed for the application in biomedical fields, including diagnosis, drug delivery, and therapeutics. The nanotechnology-based formulations have a great merit in the design of multifunctional platform for the biomedical applications. Therefore, recent trends in nanotechnology are moving onto the combination of nanotechnology and conventional therapeutic. Typically, photodynamic therapy (PDT) is one of promising techniques for the combination with nanotechnology owing to its less invasiveness. In this paper, we are going to briefly review recent advances in nanotechnology-based PDT, including selective delivery and excitation of photosensitizers, combination therapy, and multifunctional PDT.

A new member of the cyclo[n]pyrrole class of expanded porphyrins was prepared from the corresponding thiophene-containing terpyrrole precursor through use of a mild electrochemical oxidative procedure. The isolated macrocycle, featuring nine heterocyclic subunits directly connected through their α,α′-positions, is the largest cyclo[n]pyrrole derivative reported to date. The structure obtained via synchrotron radiation-based studies revealed a dimeric arrangement involving individual macrocyclic subunits.

Although exogenous porphyrin accumulation in cancer cells is important for the success of photodynamic therapies, the mechanism is not clear. We hypothesized that a newly reported transporter, heme carrier protein 1 (HCP1), is highly expressed in cancer cells, and transports porphyrins into the cells. We investigated the following three unknowns: whether cancer cells take up hematoporphyrin derivative via HCP1, whether HCP1 is involved in photodynamic therapies, and whether cancer cells highly express HCP1. First, when HCP1-overexpressed cells were treated with hematoporphyrin derivative and then exposed to an eximer laser beam, they emitted a significantly higher intensity of hematoporphyrin derivative fluorescence and became more susceptible to the laser beam than control. Second, when three other types of cancer cells with silenced HCP1 were treated with hematoporphyrin derivative and then exposed to the laser beam, they emitted a significantly lower intensity of hematoporphyrin derivative fluorescence. Third, non-cancer cells slightly expressed HCP1; on the other hand, the three other types of cancer cells clearly expressed HCP1. These results indicated that cancer cells uptake hematoporphyrin derivative via HCP1 and over-expression of HCP1 increases the efficacy of photodynamic therapies by increasing porphyrin accumulation in the cells. This is the first report about a transporter of porphyrin in cancer cells.

Four dyad systems composed of a central truxene and either one or three β-substituted zinc(II) porphyrins (ZnP: TruZnP (7) and TruTriZnP (9)) or free-bases (H₂P: TruP (6) and TruTriP (8)) have been prepared. The presence of β-methyl groups minimizes π-conjugation through the quasi right angle made by the porphyrin and the truxene planes, and renders these dyads relatively rigid. The position of the absorption and emission 0–0 peaks confirms the role of the truxene and porphyrin as the energy donor and acceptor, respectively. Selective excitation of the truxene results in an efficient singlet energy transfer (S₁ ET) from the truxene to the porphyrin unit. The rates for S₁ ET (k_ET) are extracted from the change in the fluorescence lifetime of truxene in the presence and absence of the acceptor, and are temperature independent, (TruP (6), TruTriP (8), TruZnP (7) and TruTriZnP (9) are 5.0, 1.4, 1.0 and 1.4 at 298 K and 5.9, 1.3, 2.6, and 0.86 (ns)^-1 at 77 K, respectively), consistent with their relative rigidity. These k_ET's are similar to other related but more flexible systems reported by one of us (Inorg. Chem.2011, 50, 11493–11505). The k_ET's time scale was assumed, based on modeling, to be related with hindered rotations about the truxene-porphyrin C–C bonds due to steric hexyl–hexyl interactions. This work confirms this earlier conclusion was correct.

The effect of the axial ligand fluorination of the water-soluble P(V)porphyrin complex on photosensitized protein damage was examined. The activity of singlet oxygen generation by diethoxyP(V) porphyrin was slightly improved by the fluorination of the ethoxy chains. Absorption spectrum measurements demonstrated the binding interaction between the P(V)porphyrins and human serum albumin, a water-soluble protein. Photo-irradiated P(V)porphyrins damaged the amino acid residue of human serum albumin, resulting in the decrease of the fluorescence intensity from the tryptophan residue of human serum albumin. A singlet oxygen quencher, sodium azide, could not completely inhibit the damage of human serum albumin, suggesting that the electron transfer mechanism contributes to protein damage as does singlet oxygen generation. The decrease of the fluorescence lifetime of P(V)porphyrin by human serum albumin supported the electron transfer mechanism. The estimated contributions of the electron transfer mechanism are 0.57 and 0.44 for the fluorinated and non-fluorinated P(V)porphyrins, respectively. The total quantum yield of the protein photo-oxidation was slightly enhanced by this axial fluorination.

The mechanism of the reaction between ferric Caldariomyces fumago chloroperoxidase (CCPO) and meta-chloroperoxybenzoic acid (mCPBA) has been examined. It has previously been established that an Fe(IV)-oxo porphyrin radical species known as Compound I (Cpd I) is formed by two-electron oxidation of the native ferric enzyme by a variety of oxidants including organic peracids and hydroperoxides. Cpd I can return to the ferric state either by direct oxygen insertion into an organic substrate (e.g. a P450 oxygenase-like reaction), or by two consecutive one-electron additions, the first resulting in an intermediate Fe(IV)-oxo species known as Compound II (Cpd II). There has been much debate over the role of Cpd II and the details of its structure. In the present study, both CCPO Fe(IV)-oxo intermediates are formed, but unlike most CCPO reactions, Cpd I and Cpd II are formed using the same reactant, mCPBA. Thus, the peracid is used as an oxo donor to produce Cpd I and then as a reductant to reduce Cpd I to Cpd II, and finally, Cpd II to the ferric state. The observation of saturation kinetics with respect to mCPBA concentration for each step is consistent with the formation of CCPO-mCPBA complexes in each phase of the reaction. The original reaction mechanism for ferric CCPO with mCPBA was hypothesized to involve a scrambling mechanism with a unique Fe-OOO-C(O)R intermediate formed with no observed Cpd II intermediate. The data reported herein clearly demonstrate the formation of Cpd II in returning the oxidized enzyme back to its native ferric state.

Bacteriochlorins are attractive candidates as photosensitizers for photodynamic therapy (PDT) due to their intense absorption in the near-infrared (NIR) region of the spectrum where light transmission through tissue is maximal. Many naturally occurring bacteriochlorins are inherently unstable due to adventitious atmospheric oxidation. A de novo synthesis affords bacteriochlorins that contain a geminal dimethyl group in each reduced pyrrole ring to increase stability against oxidation. Here, three new synthetic bacteriochlorins, each bearing a single side-chain containing one or two positive charges, were investigated for their in vitro PDT activity against HeLa human cancer cells. All bacteriochlorins were active at low nanomolar concentration when activated with NIR light; those bearing a single positive charge exhibited faster uptake and higher activity. The bacteriochlorins were localized in mitochondria, lysosomes and endoplasmic reticulum as shown by organelle specific fluorescent probes. Cell death was via apoptosis as shown by cell morphology and nuclear condensation. Taken together, the results show the importance of appropriate peripheral groups about a photosensitizer for effective PDT applications.

A novel dipyrrolyl metal-coordination ligand dimer directly connected at the meso positions showed the formation of a Zn^II-bridged coordination polymer and the spontaneous transformation to a meso–meso- and singly β–β-fused tetrapyrrolyl molecule in solution by C–C bond formation and concomitant proton migration.

Zinc 5-(4-carboxy-phenylethynyl)-10,20-biphenylporphines bearing various substituents on the 10,20-phenyl rings are studied for their electrochemical and spectroelectrochemical properties. Cyclic voltammetry and optically transparent thin-layer electrochemical measurements suggest that the first reductions of these porphyrins should be the reduction reaction of the carboxylic protons. For the porphyrin ring reactions, our study shows that the redox properties can be significantly affected by the alkoxyl chains on the 10,20-phenyl rings.

This paper describes the preparation and spectral properties of a near-infrared fluorophore in which two bis(2-picolyl)amino moieties are axially linked to a silicon(IV) phthalocyanine core. The effects of various metal ions on its absorption and fluorescence spectra have been examined. The results indicate that this compound shows a high sensitivity and moderate selectivity toward Zn²⁺ ion.

The design and synthesis of new molecular hybrids composed of protoporphyrin IX (PPIX) and vitamin B₁₂ via copper catalyzed alkyne azide cycloaddition reaction is described. New, clickable aminoazide and aminoalkyne linkers were prepared and subsequently attached to PPIX (via vinyl group) and to vitamin B₁₂ giving desired building blocks. Preliminary results showed that respective water soluble hybrids were formed under CuAAC reaction. Gratifyingly, Cu incorporation into the PPIX core was avoided, which was important for further biological studies.

We report the synthesis of Fe(TalkylP)(OClO₃)] (alkyl = ethyl and propyl) and [Fe(TPrP)(THF)₂]ClO₄, which are characterized by UV-vis, EPR, X-ray crystallography, and solid-state magnetic susceptibilities. The macrocycles of all three complexes are ruffled, all of the structural features for [Fe(TEtP(OClO₃)] and [Fe(TPrP)(OClO₃)] are characteristic of the nearly pure S = 3/2 state, while the structural parameters for [Fe(TPrP)(THF)₂]ClO₄ feature a pure intermediate-spin (S = 3/2) state, which are all consistent with EPR and magnetic data. It is clear from these studies that the ruffled conformation plays a significant role in affecting the extent of S = 3/2 character.

In order to improve the therapeutic effect of zinc phthalocyanines (ZnPc), a photoactive nanodrug was prepared with acetylated chondroitin sulfate (AcCS), utilizing a simple chemical method. AcCS/ZnPc nanodrugs have a unimodal size distribution below 200 nm and a negative surface charge due to AcCS located on the nanodrug surface. In organic solvent such as DMSO or DMF, it has strong fluorescence intensity and generates abundant singlet oxygen. However, in aqueous solvent, AcCS/ZnPc nanodrugs developed a self-organized form which induced reducing fluorescence intensity and singlet oxygen generation. The cellular uptake of the nanodrug was determined using a cell lysis test and confocal microscopy observation. The results indicated that cellular internalization efficiency of the nanodrug was 1.7–2.1 times higher than that of free ZnPc. Also, the phototoxicity of the nanodrug was detected via MTT assay with or without light. Although free ZnPc did not exhibit cytotoxicity in both light and dark condition, the nanodrug exhibited increasing cytotoxicity after irradiation. We therefore suggest that AcCS/ZnPc nanodrugs may have promising applications as new photodynamic agents for the clinical treatment of various tumors.

The visible-light-driven dechlorination of 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) was carried out in the presence of a hydrophobic vitamin B₁₂, heptamethyl cobyrinate perchlorate and Rhodamine B. DDT was successfully dechlorinated to form 1,1-bis(4-chlorophenyl)-2,2-dichloroethane (DDD) as the mono-dechlorinated product upon visible light irradiation with a tungsten lamp (λ > 440 nm). Upon prolonged visible light irradiation to DDT, DDMU (1-chloro-2,2-bis(4-chlorophenyl)ethylene), DDMS (1-chloro-2,2-bis(4-chlorophenyl)ethane) and DCS (trans-4,4′-dichlorostilbene) were obtained as the di- and tri-dechlorinated products. The use of the photostable organic sensitizer enabled prolonged photocatalysis via a noble-metal-free process. The vitamin B₁₂ derivative was replaced by an imine/oxime-type cobalt complex although the cobalt complex system showed a lower catalytic activity than the B₁₂ derivative system. The dechlorination mechanism in the B₁₂-Rhodamin B system was investigated by various methods such as UV-vis absorption and fluorescence quenching.

The use of protonless ¹³C′–¹³C′ EXSY (COCO-EXSY) is proposed here to measure electron self-exchange rates. The experiment is compared to the commonly employed ¹H and ¹⁵N EXSY experiments using as a reference system human cytochrome c. In COCO-EXSY, the exchange peaks are stronger than in the other experiments with respect to the self peaks and their intensity is less dependent on the choice of the EXSY mixing time. The use of ¹³C directed detection may be essential for all those cases where T₂ relaxation is detrimental, as in the case of proteins containing highly paramagnetic metal centers, or rotating slowly in solution, or where the amide signals are difficult to detect due to chemical or conformational exchange. The proposed experiment has a general applicability and can be used to monitor exchange phenomena different from electron self-exchange.

Two zinc(II) phthalocyanines (ZnPcs) were conjugated with a monoclonal antibody (MAb) directed against carcinoembryonic antigen (CEA), using an in situ activated carboxylic acid on the ZnPcs. The bioconjugate with the highest ZnPc/MAb ratio of 3 was investigated in vitro for its ability to target and fluorescently label human colorectal HT-29 cells. The ZnPc-CEA MAb 2 was observed to efficiently target HT-29 cells, about 37 times more than unconjugated ZnPc. Furthermore, in the presence of a 4-fold excess of unlabelled anti-CEA antibody, the fluorescence signal of 2 was reduced by ~90% showing that the targeting is CEA-mediated. These studies further confirm the high specificity of Pc-antibody conjugates for antigens over-expressed on tumor cells and warrant further investigations of these immunoconjugates and their derivatives for imaging of colorectal cancer.

Covalently linked BF₂-oxasmaragdyrin-BODIPY and BF₂-oxasmaragdyrin-ferrocene dyads were synthesized by coupling of meso-triaryl oxasmaragdyrin containing meso-iodophenyl group with meso-(p-ethynylphenyl) borondipyrromethene and α-ethynyl ferrocene respectively under mild Pd(0) coupling conditions. NMR, absorption and electrochemical studies indicated that the two moieties in the dyads retain their individual characteristic features. The fluorescence studies indicated a possibility of photoinduced singlet-singlet energy transfer from BODIPY unit to BF₂-oxasmaragdyrin unit in BF₂-oxasmaragdyrin-BODIPY dyad and photoinduced electron transfer from ferrocene unit to excited state of BF₂-oxasmaragdyrin unit in BF₂-oxasmaragdyrin-ferrocene dyad.