Vanadium Schiff Base Complexes: Chemistry, Properties, and Concerns about Possible Therapeutic Applications

Abstract

We discuss aspects related to the speciation of vanadium compounds (VCs) with salen-type ligands, as well as V IV O(acac) 2 and V IV O(phen) 2 (SO 4 ), namely the stability of their V IV and V v complexes in aqueous aerobic solutions at pH∼7, and consequences on the study of toxicity, insulin mimetic and nuclease activity studies. We show that in these aerobic aqueous solutions V IV Schiff-base (SB) complexes of the salen-type are normally not stable to oxidation to V V and to hydrolysis of the ligand. V IV O(phen) 2 (SO 4 ) and V IV O(acac) 2 and are also not stable to oxidation, and a significant decomposition of these complexes occurs within the first 30 minutes after their dissolution. Therefore, when these VCs are used for in vitro or in vivo studies the active species is not known. Reduction of the salen SB to give amine compounds yields salan ligands which form much more stable complexes than the parent SB. When dissolved in non-degassed aqueous solutions at pH∼7 the V IV -salan compounds oxidise to V V -salan complexes, but no hydrolysis is detected. At least with the cell lines tested these VCs are not toxic possibly because they do not enter the cells significantly. We emphasize that to understand if the VCs enter the cells or not is an important point to sort out in insulin-mimetic studies. In fact we also report some studies of nuclease activity of several salen and salan VCs, as well as of V IV O(acac) 2 and V IV O(phen) 2 (SO 4 ) with plasmid DNA. Many of these VCs show nuclease activity even in the absence of activating agents, so toxicity resulting from this may occur. We also study several parameters relevant for the nuclease activity of VCs, namely the nature and concentration of the buffer used.