Vanadium(V)-substituted Keggin-type heteropolyoxotungstophosphates as electron transfer and antimicrobial agents: oxidation of glutathione and sensitization of MRSA towards β-lactam antibiotics

Abstract

Glutathione (GSH) undergoes facile electron transfer with vanadium(V)-substituted Keggin-type heteropolyoxometalates, $[ {\text{PV}}^{\text{V}} {\text{W}}_{ 1 1} {\text{O}}_{ 4 0} ]^{{ 4 { - }}}$ (HPA1) and $[ {\text{PV}}^{\text{V}} {\text{V}}^{\text{V}} {\text{W}}_{ 1 0} {\text{O}}_{ 4 0} ]^{{ 5 { - }}}$ (HPA2). The kinetics of these reactions have been investigated in phthalate buffers spectrophotometrically at 25 °C in aqueous medium. One mole of HPA1 consumes one mole of GSH and the product is the one-electron reduced heteropoly blue, $[ {\text{PV}}^{\text{IV}} {\text{W}}_{ 1 1} {\text{O}}_{ 40} ]^{ 5- }$. But in the GSH-HPA2 reaction, one mole of HPA2 consumes two moles of GSH and gives the two-electron reduced heteropoly blue $[ {\text{PV}}^{\text{IV}} {\text{V}}^{\text{IV}} {\text{W}}_{ 10} {\text{O}}_{ 40} ]^{ 7- }$. Both reactions show overall third-order kinetics. At constant pH, the order with respect to both [HPA] species is one and order with respect to [GSH] is two. At constant [GSH], the rate shows inverse dependence on [H⁺], suggesting participation of the deprotonated thiol group of GSH in the reaction. A suitable mechanism has been proposed and a rate law for the title reaction is derived. The antimicrobial activities of HPA1, HPA2 and $[ {\text{PV}}^{\text{V}} {\text{V}}^{\text{V}} {\text{V}}^{\text{V}} {\text{W}}_{ 9} {\text{O}}_{ 4 0} ]^{{ 6 { - }}}$ (HPA3) against MRSA were tested in vitro in combination with vancomycin and penicillin G. The HPAs sensitize MRSA towards penicillin G.