Amphiphilic peroxynitrite decomposition catalysts in liposomal assemblies

Abstract

For these amphiphilic analogs of FeTMPyP and MnTMPyP, the polarity of the environment of the metalloporphyrin headgroup is intimately related to the efficiency of the catalyst; a polar aqueous environment is essential for effective catalysis of ONOO- decomposition. Thus, catalysts 1b. and 2b. react rapidly with ONOO- and are potential therapeutic agents that, unlike their water-soluble TMPyP analogs, could be administered as liposomal formulations in SLs. These SL-bound amphiphilic metalloporphyrins may prove to be highly effective in the exploration and treatment of ONOO- related disease states.

meso-Tetra(pentafluorophenyl)porphyrin as an Efficient Platform for Combinatorial Synthesis and the Selection of New Photodynamic Therapeutics using a Cancer Cell Line

“…Because of the 3 − charge of the free base, these compound stabilize high valent metal ions, including some that are suitable for contrast agents such as Ga(III). 71 Since the perfluorophenyl groups in triPCF 15 are orthogonal to the corrole macrocycle, similar to those on the porphyrin TPPF 20 , the reactivity of the para fluoro group was expected to be similar.…”

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AbstractThe four para fluoro groups on 5,10,15,3,4,5, ) are known to react with a variety of nucleophiles, but the reaction conditions for this substitution reaction depend on the nature of the nucleophiles, e.g. primary amines versus thiols.

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Catalytic antioxidants to treat amyotropic lateral sclerosis

“…In the mid 1990s, the ability of this class of compounds to react very rapidly with peroxynitrite (second-order rate constants of ∼ 10 6 -10 8 M -1 s -1 ) and to catalytically decompose it became evident [31,33,36,37]. By this time, peroxynitrite was being recognised as a potent endogenous oxidant and cytotoxin, which could account for much of the oxidative injury previously ascribed to superoxide, NO, hydrogen peroxide and even the hydroxyl radical [38][39][40].…”

“…Many of these manganese porphyrins have been shown to react with superoxide, peroxynitrite, carbonate radical and nitric oxide (NO) at rates fast enough to out-compete other biomolecular targets [30]. In general, the manganese porphyrins require endogenous reductants -such as ascorbate, glutathione, NADPH and so on -to regenerate the metal-reduced (Mn 3+ or Mn 2+ ) forms [31,32] and to quench secondary reactive species produced [2,[33][34][35]. However, by reacting with oxidants such as peroxynitrite (and then being re-reduced by endogenous reductants such as ascorbate and glutathione) faster than the direct reaction of peroxynitrite with these reductants, the metalloporphyrins greatly amplify the effectiveness of endogenous reductants at detoxifying reactive species.…”

“…Thus contamination of MnTCPP preparations with differing amounts of FeTCPP has been considered as a possible explanation for the variability in biological activity observed with MnTCPP from different sources. Unlike MnTCPP, FeTCPP (and other iron porphyrins) can catalytically decompose peroxynitrite even in the absence of added reductants [33,36]. For all of these reasons, FeTCPP was chosen as the first metalloporphyrin to be tested in the G93A ALS mouse model.…”