Interaction and Reaction of the Antioxidant Mn^III [Meso-Tetrakis(4-NMethyI Pyridinium) Porphyrin] with the Apoptosis Reporter Lipid Phosphatidylserine

Abstract

In the present study, the binding of the cationic Mn III TMPyP [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 Mn III TMPyP 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 Mn III TMPyP 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 Mn II /Mn III (+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 O 2-• to O 2 by the porphyrin. Mn III TMPyP 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 (Mn IV =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.

Photodamage in a Mitochondrial Membrane Model Modulated by the Topology of Cationic and Anionic Meso‐Tetrakis Porphyrin Free Bases

“…TMPyP is a hydrophilic porphyrin, and it is not expected to be found buried in the bilayer. Thus, these spectral changes can be assigned to an electrostatic interaction of the positively charged metal‐free TMPyP meso ligands with the negatively charged interface of PC/CL .…”

“…Biological membranes are targets for the action of PDT. Therefore, numerous studies have been concerned with the interaction of porphyrins with liposomes and other membrane mimetic models . However, literature lacks comparative studies involving photodynamic action of hydrophilic porphyrins on mitochondrial membrane models.…”

Technological Applications of Porphyrins and Related Compounds: Spintronics and Micro-/Nanomotors

“…Theoretical studies of porphyrins have also gained relevance [4,[20][21][22][23]. Synthesis of porphyrins is principally motivated by improved use in photodynamic therapy, energy, and catalysis [24][25][26]. The catalytic and photochemical properties of porphyrins are dependent on the presence and type of the central metal ion with axial ligands, the peripheral decoration, and microenvironment of the ring [11,27].…”

Free-Base and Metal Complexes of 5,10,15,20-Tetrakis(NMethyl Pyridinium L)Porphyrin: Catalytic and Therapeutic Properties

“…The potential values of Mn 2+ /Mn 3+ redox process were found to be E 1/2 =94 mV for ortho Mn 3+ TMPyP and E 1/2 = 42 and 50 mV, respectively, for meta and para isomers. However, in a heterogeneous system, Araujo-Chaves et al [20] have reported that the para isomer has the redox potential increased by the association with the negatively charged interface of lipid bilayers. Interestingly, the association of para Mn 3+ TMPyP to PC/PS liposomes at physiological pH exhibited a redox potential of +110 mV vs NHE.…”

“…Para MnTMPyP exhibits a lower redox potential value that disfavors SOD activity [19]. However, the association of para MnTMPyP to negatively charged membranes (phosphatidylcholine (PC)/phosphatidylserine (PS)) modulates its redox potential toward a more efficient SOD activity [20]. Thus, the study of Araujo-Chaves et al [13] is an example of the modulation of a porphyrin activity by the microenvironment.…”