Metalloporphyrin-based biomimetic catalysts, sensors, and redox-(photo)active therapeutics

A.M. BARBOSA; C.G.C. MAIA; G.M. UCOSKI; M.S. DI NEZIO; W.D. FRAGOSO; M.S. RIBEIRO; S. NAKAGAKI; V.H.A. PINTO; A.C.V. MASCARENHAS; J.F. SARMENTO-NETO; C.V. LIMA; BUENO-JANICE; G.D. PIERINI; C.G. ANDRADE; M.F. PISTONESI; M.E. CENTURIÓN; M.G. FONSECA; S.G. LEMOS; A. FONTES; BATINIC-HABERLE; E.R.M. GOMES; B.S. SANTOS; J.S. REBOUÇAS

Congreso; XIX BMIC? VI LaBIC ? VIII Brazilian Meeting on Rare Earths September; 2018

Water-soluble porphyrins have allowed the effective design of biomimetic catalysts, metal sensors, and experimental therapeutics. Mn(III) 2-N-alkylpyridylporphyrins, including A3B-type Mn porphyrins, have been prepared and investigated as biomimetic models of oxidoreductase enzymes, such as cytochromes P450, peroxidases, and superoxide dismutases (SOD). The immobilization of Mn porphyrins (MnPs) onto inert supports, such as silicates (e.g., silica gel, SBA-15) or clay minerals (e.g., vermiculite, palygorskite) yielded organic-inorganic hybrid materials as oxidation catalysts with excellent recyclability. The inorganic supports mimicked P450 apoprotein by increasing MnP oxidative stability. Empirical structure-activity relationships guided the design of SOD mimics based on MnPs of tailored lipophilicity and electrostatic facilitation. The redox properties of MnPs allowed the development of an alternative, electrochemical method for measuring MnPs in biological samples, as well as the development of modified electrodes for H2O2 electrocatalysis. An anionic porphyrin was found suitable for the analytical determination of Zn(II) in commercial propolis extracts without sample pretreatment, the method being amenable to adaptation to other biological matrices. Zn(II) 2-N-alkylpyridylporphyrin-based photosensitizers were shown to impose an indirect redox imbalance on the promastigote and amastigote forms of Leishmania braziliensis under photodynamic therapy (PDT) conditions. PDT associated with ZnTE-2-PyP4+ represents a promising alternative to cutaneous leishmaniasis treatment. Preclinical studies on in vitro and in vivo rat models showed that MnTE-2-PyP5+ reduced Ca2+ signaling on cardiomyocytes and effectively prevented and treated cardiac arrhythmias preserving heart contractile function.