Mononuclear and dinuclear peroxotungsten complexes with co-ordinated dipeptides as potent inhibitors of alkaline phosphatase activity

Abstract

New molecular peroxotungstate(VI) complexes with dipeptides as ancillary ligands of the type, [WO(O 2 ) 2 (dipeptide) (H 2 O)].3H 2 O, dipeptide ¼ glycyl-glycine or glycyl-leucine, have been synthesized and characterized by elemental analysis, spectral and physico-chemical methods including thermal analysis. The complexes contain side-on bound peroxo groups and a peptide zwitterion bonded to the metal centre unidentately through an O(carboxylate) atom. Investigations on certain biologically important key properties of these compounds and a set of dimeric compounds in analogous co-ligand environment, Na 2 [W 2 O 3 (O 2 ) 4 (dipeptide) 2 ].3H 2 O, dipeptide ¼ glycyl-glycine and glycyl-leucine, reported previously by us revealed interesting features of the compounds. Each of the compounds despite having a 7 co-ordinated metal centre exerts a strong inhibitory effect on alkaline phosphatase activity with a potency higher than that of the free dipeptide, tungstate or peroxotungstate. The compounds exhibit remarkable stability in solutions of acidic as well as physiological pH and are weaker as substrate to the enzyme catalase, compared to H 2 O 2 . The mononuclear and dinuclear peroxotungsten compounds are efficient oxidants of reduced glutathione (GSH), a reaction in which only one of the peroxo groups of a diperoxotungsten moiety of the complexes was found to be active.

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.…”

“…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.…”

“…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. Pertinent here is to mention that, although a few reports are available on peptide containing pV compounds [27][28][29][30], pW compounds with biogenic coligands have so far received scant attention [24,26,31,32].…”

“…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.…”