Abstract
In the present study, the binding of the cationic MnIIITMPyP [meso-tetrakis (4-N-methyl pyridinium) porphyrin] to negatively charged membrane models containing phosphatidylcholine (PC)/ phosphatidylserine (PS) and the porphyrin reactivity with PS-derived peroxides (LOOH) were evaluated. This investigation is relevant due to the participation of PS in cell signaling and apoptosis. Addition of PC/PS liposomes to MnIIITMPyP solutions led to spectral changes of the porphyrin electronic absorption spectrum suggestive of electrostatic interactions with the negatively charged interface provided by PS. The binding of MnIIITMPyP to PC/PS liposomes was corroborated by the quenching of the fluorophore merocyanine 540. In addition total energy calculations of saturated and unsaturated PS based on the spinpolarized variant of KS-DFT were used to support some experimental data. Cyclic voltammetry analysis revealed that the association to PC/PS liposomes shifted the redox potential of the MnII/MnIII (+87 mV vs NHE, in aqueous buffered solution) couple to a more positive value to (+110 mV vs NHE). This event favors the oxidation of O2 -• to O2 by the porphyrin. MnIIITMPyP was able to react with the lipid-derived peroxides as evidenced by spectral changes of the porphyrin consistent with the generation of a high valence state (MnIV=O) of the catalyst. The spectral changes were not observed when biological lipids containing unsaturated PC and PS were replaced by the corresponding dipalmitoyl (DP)- derived: DPPC/DPPS.
Keywords: MnIIITMPyP [meso-tetrakis (4-N-methyl pyridinium) porphyrin], Phosphatidylserine, Liposomes, Electronic absorption spectroscopy fluorescence spectroscopy, Electrostatic interaction, Superoxide dismutase mimetics.
3