New peroxovanadium compounds containing biogenic co-ligands: synthesis, stability and effect on alkaline phosphatase activity

Abstract

A set of new diperoxovanadate(V) complexes with the dipeptides glycyl-glycine or glycyl-leucine as ancillary ligands of the type, A[VO(O 2 ) 2 (peptide)(H 2 O)] Á H 2 O, A = Na or K have been synthesized and characterized by elemental analysis, thermal analysis, magnetic susceptibility and spectral studies. The complexes contain side-on bound peroxo groups and a dipeptide zwitterion as co-ligand, binding the metal center unidentately through O (carboxylate) atom. The compounds are highly stable toward decomposition in solutions of acidic as well as physiological pH and serve as weak substrates to catalase, undergoing degradation in the presence of the enzyme at a rate much slower than H 2 O 2 . The compounds stoichiometrically oxidize GSH to GSSG. On comparing the GSH oxidizing ability of these compounds with those of previously reported peroxotungsten compounds containing similar co-ligands, a significant difference was noted. The compounds induce a strong inhibitory effect on alkaline phosphatase activity with a potency higher than that of the free peptides, vanadate, or peroxovanadate.

Kinetics of Inhibition of Rabbit Intestine Alkaline Phosphatase by Heteroligand Peroxo Complexes of Vanadium(V) and Tungsten(VI)

“…The extent and initial rates of degradation of the compounds ( Table 2) under the effect of catalase action was found to be comparable to that of diperoxo compounds vanadium and tungsten synthesized and examined previously by us [24,25], indicating their similarity with respect to number of peroxide and probably the pattern of coordination to the respective metal center.…”

“…Each of the complexes pV1 and pW1, like pV2 and pW2, has been found to be an oxidizing agent with respect to reduced GSH [24][25][26]. The amounts of GSH oxidized at two different concentrations of 5 and 10 μM of the complexes are presented in Fig.…”

“…The solution was incubated at 30°C. The compound was then added to the test solution and aliquots of 5 ml were pipetted out and titrated for peroxide content after stopping the reaction by adding it to cold sulfuric acid (0.7 M, 100 ml) at time 5,10,15,20,25, and 40 min of starting the reaction. Three concentrations of peroxo compounds (0.05, 0.1, 0.2 mM) were tested.…”

“…We have recently synthesized a series of peroxo compounds of V(V) and W(VI) containing amino acids and dipeptides as coligands with reasonable stability in solution and capable of inhibiting activity of ALP [24][25][26]. Inhibitor potency of these compounds appeared to be sensitive to the coligand environment.…”

“…Inhibitor potency of these compounds appeared to be sensitive to the coligand environment. As a direct sequel to our work on peroxometallates [24][25][26][27][28][29] and in order to gain a better understanding on the mode of their interaction with enzymes, we deemed it imperative to investigate the kinetics of inhibition of ALP by the aforementioned pV and pW compounds and to extend our studies to other well-defined and stable peroxometallates containing biogenic ancillary ligands. For the present study, we have focused on synthesizing newer peroxo compounds of V and W possessing a tripeptide as ancillary ligand with appropriate characteristics of solubility and stability.…”