Narrow Results

Proton-coupled electron transfer (PCET) is central to the reactivity of porphyrins. The coupling of the electron to the proton is central to a porphyrin’s ability to catalyze energy conversion reactions of which the hydrogen evolution reaction (HER) is exemplary. To understand the mechanistic details of the PCET chemistry of porphyrins and related macrocyclic congeners, we have designed hangman constructs that allow a proton, placed in the secondary coordination sphere (off of the hangman backbone), to be coupled to redox transformations at the macrocycle. For metals whose reduction potentials are positive of the porphyrin macrocycle, such as Co and Fe, HER catalysis is confined to PCET transformations of the metal center where the active catalyst for HER is a reduced metal hydride. Alternatively, the reduction potentials of Ni, Zn, and 2H (freebase) porphyrins allow for redox non-innocence of the macrocycle; here the active “hydridic” catalyst is a phlorin, which gives rise to elaborate HER reaction sequences. Beyond HER catalysis, redox non-innocence of Ni, Zn, and 2H porphyrins and related compounds has been informative for providing detailed mechanistic insight into the multi-site PCET hydrogenation of olefinic bonds of the macrocycle. This mini-review unravels the PCET dichotomy between the metal and macrocycle in promoting HER catalysis and novel chemical transformations that give rise to unusual macrocyclic structures.

Combined therapy is currently a popular method for increasing the efficiency of antitumor treatment. It involves the use of two different tumor treatment methods, namely, chemotherapy and PDT. Combining a cytotoxic agent and a photosensitizer in a single molecule results in a synergistic antitumor effect that overcomes the multiple drug resistance and reduces the therapeutic drug doses. In this work, pyridine-containing natural chlorins were obtained by introducing a pyridine group into 13¹-$N$-(4-aminobutyl)amide of chlorin $e_6$ and its bacteriochlorin analogue, $O$-propyloxime-$N$-propoxybacteriopurinimide as well as $N$-aminobacteriopurinimide methyl ester. Moreover, a terpyridine residue was introduced as an external chelating moiety into $N$-hydroxypurpurinimide and $N$-aminobacteriopurinimide, and platinum complexes of all the above photosensitizers were obtained. The interactions of the latter with DNA were simulated and the lead compound, the platinum complex of pyridine derivative 13¹-$N$-(4-aminobutyl)amide chlorin $e_6$, which may become a potential agent for combined photodynamic and chemotherapy in oncology, was selected. The ability of the compounds obtained to manifest photodynamic and chemocytotoxic effects on tumor cells of various genesis was shown.

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer (PS) play key roles in the treatment efficacy. In this study, a novel PS, 5,10,15,20-tetrakis((5-dipropylamino)pentyl)-chlorin (TDPC) which displayed a characteristic long wavelength absorption peak at 650 nm were synthesized. It also shows a singlet oxygen generation rate of 4.257 min^-1. Generally, TDPC is localized in mitochondria and nucleus of cell. After light irradiation with 650 nm laser, it can kill many types of cell, in addition, TDPC–PDT can destroy ECA-109 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following TDPC–PDT. The results showed that it either increased or decreased, among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. In general, TDPC is an effective antitumor PS in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new PSs.

In this study, a novel photosensitizer meso-tetra (3-pyrrolidinomethyl-4-methoxyphenyl) chlorin (TPMC) was reported. It displays a characteristic long wavelength absorption peak at 656 nm and it shows a singlet oxygen quantum yield of 0.48. After light irradiation with 650 nm laser, it can kill Eca-109 and SMMC-7721 cells in vitro (25 mW/cm², 1.2 to 3.6 J/cm²) and destroy Eca-109 tumor in nude mice (50 mW/cm², 90 J/cm²). It has the perspective to be developed as a new anti-tumor drug in photodynamic therapy (PDT) photodiagnosis, and deserves further investigation.