Chlorin and bacteriochlorin derivatives of 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK-MEL-188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time-dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.

New halogenated water-soluble chlorin and bacteriochlorin as photostable PDT sensitizers: synthesis, spectroscopy, photophysics, and in vitro photosensitizing efficacy.

Mechanistic studies on metalloporphyrin epoxidation reactions with hydrogen peroxide: evidence for two active oxidative species

A series of substituted tetraphenylporphyrin iron chloride complexes [RTPPFe(III)Cl, R=o/p-NO₂, o/p-Cl, H, o/p-CH₃, o/p-OCH₃] were synthesized by a novel universal mixed-solvent method and the spectral properties of free base porphyrins and iron porphyrin compounds were compared with each other. The experimental results showed that the one-pot mixed solvent method was superior to the two-step method in the yields, reaction time and workup of reaction mixtures for the synthesis of iron porphyrin compounds. The highest yields (28.7%-40.4%) of RTPPFe(III)Cl were obtained in the mixed solvents propionic acid, glacial acetic acid and m-nitrotoluene under reflux for 2 h. A detailed analysis of ultraviolet-visible (UV-vis), infrared (IR) and far-infrared (FIR) spectra suggested the transformation from free base porphyrins to iron porphyrins. The red shift of the Soret band in ultraviolet-visible spectra due to the presence of p-nitrophenyl substituents and the blue shift of Fe-Cl bond of TPPFeCl in far-infrared spectra were further explained by the electron transfer and molecular planarity in the porphyrin ring.

Synthesis, Characterization and Spectral Properties of Substituted Tetraphenylporphyrin Iron Chloride Complexes

Superoxide is involved in a plethora of pathological and physiological processes via oxidative stress and/or signal transduction pathways. Superoxide dismutase (SOD) mimics have, thus, been actively sought for clinical and mechanistic purposes. Manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is one of the most intensely explored "SOD mimics" in biology and medicine. However, we show here that this claimed SOD activity of MnTBAP in aqueous media is not corroborated by comprehensive structure-activity relationship studies for a wide set of Mn porphyrins and that MnTBAP from usual commercial sources contains different amounts of noninnocent trace impurities (Mn clusters), which inhibited xanthine oxidase and had SOD activity in their own right. In addition, the preparation and thorough characterization of a high-purity MnTBAP is presented for the first time and confirmed that pure MnTBAP has no SOD activity in aqueous medium. These findings call for an assessment of the relevance and suitability of using MnTBAP (or its impurities) as a mechanistic probe and antioxidant therapeutic; conclusions on the physiological and pathological role of superoxide derived from studies using MnTBAP of uncertain purity should be examined judiciously. An unequivocal distinction between the biological effects due to MnTBAP and that of its impurities can only be unambiguously made if a pure sample is/was used. This work also illustrates the contribution of fundamental structure-activity relationship studies not only for drug design and optimization, but also as a "watchdog" mechanism for checking/spotting eventual incongruence of drug activity in chemical and biological settings.

Pure manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is not a superoxide dismutase mimic in aqueous systems: a case of structure–activity relationship as a watchdog mechanism in experimental therapeutics and biology

Work during the last decade laid down the basis for biomimetic oxidation catalysis, which has become an established technique. Preliminary work relied on the use of metal complexes of 5,10,15,20-tetrakisphenylporphyrin (TPP), but these proved to be inadequate to perform the catalytic function. Further, derivatives of TPP with suitable and adequately positioned substituents, allowed the preparation of high performance catalysts, in terms of catalytic efficiency and stability, for some selected oxidations under specific reaction conditions and for a diversity of oxygen donors. The first oxidations were achieved using the ‘special’ oxygen donor iodosylbenzene, but cheaper and generally available oxidants such as sodium hypochlorite or hydrogen peroxide are presently used as the oxidants. Catalysts capable of promoting stereoselective catalysis are reported. Conditions for the efficient use of the catalysts so far reported require particular specificities and the catalytic activity is only shown, in the majority of the reported works, in the presence of selected species to act as axial ligands to the metal ion of the catalyst. Specific porphyrin structures were reported where the addition of a specific axial ligand can be avoided.

State of the art in the development of biomimetic oxidation catalysts

Improved syntheses of 5,10,15,20-tetrakisaryl- and tetrakisalkylporphyrins

Improvements are described to the synthesis of the catalytically important 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 1(R = H) and [2,3,7,8,12,13,17,18-octachloro-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III)3(R = Cl) which enable large-scale preparation of such compounds to be carried out easily. A comparative study of the catalytic performance of the manganese complexes of these two porphyrins proved that, contrary to earlier expectations, the manganese complex of 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin is the most stable and efficient catalyst for epoxidation when using sodium hypochlorite as oxidant. With [2,3,7,8,12,13,17,18-octachloro-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III)3, chlorinated products tend to be formed and these can be the dominant products for some substrates.

5,10,15,20-Tetrakisaryl- and 2,3,7,8,12,13,17,18-octahalogeno-5,10,15,20-tetrakisarylporphyrins and their metal complexes as catalysts in hypochlorite epoxidations

M. Luisa P. G. Nunes

Papers

Improved syntheses of 5,10,15,20-tetrakisaryl- and tetrakisalkylporphyrins

5,10,15,20-Tetrakisaryl- and 2,3,7,8,12,13,17,18-octahalogeno-5,10,15,20-tetrakisarylporphyrins and their metal complexes as catalysts in hypochlorite epoxidations