Comparative studies on manganese-based SOD mimetics, including the phosphate effect, by using global spectral analysis

Abstract

Stopped-flow measurements have been successfully combined with time-resolved UV/vis spectroscopy and global spectral analysis of superoxide decay for the comparative study of catalytic activity of putative manganese SOD (superoxide dismutase) mimetics known in the literature. The SOD activity of the studied complexes decreases in the following order: a) M40403>Mn(III)TM-4-PyP(5+)>Mn(II)pyane >>EUK-113 at pH 7.4 (M40403=([manganese(II)dichlorido{(4R,9R,14R,19R)-3,10,13,20,26-pentaazatetracyclo[20.3.1.0.4,9014,19]hexacosa-1(26),-22(23),24-triene}], Mn(III)TM-4-PyP(5+)=Mn(III)meso-tetrakis(N-methylpyridinium-4-yl)porphyrin, Mn(II)Pyane=Mn(II)trans-2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]-octadeca-1(18),14,16-triene, EUK-113=[manganese(III)acetato(6,6'-((1E,1'E)-(ethane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenolate)]) in Hepes buffer (Hepes=4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid), b) Mn(III)TM-4-PyP(5+)>M40403≅Mn(II)pyane >>EUK-113 at pH 8.1 in Hepes buffer and c) Mn(III)TM-4-PyP(5+)≅Mn(II)pyane>MnCl(2)>M40403≅EUK-113 at pH 7.4 in phosphate buffer. MnCl(2) in Hepes, Mn(III)TSPP(3-), Mn(III)TBAP(3-), Mn(III)acetate, Mn(II)lactate and Mn(II)EDTA do not exhibit SOD activity (Mn(III)TSPP(3-)=Mn(III)mesotetrakis(benzoic acid)porphyrin, Mn(III)TBAP(3-)=Mn(III)mesotetrakis(4-sulfonatophenyl)porphyrin). MnCl(2) possess SOD activity that is comparable with those of other mimetics in the presence of phosphate. Our results demonstrate that phosphate anions, independent of ionic strength effect, influence the activity of manganese SOD mimetics, which is crucial for understanding and comparing their biological activity.