Formation and Structure of 1:1 Complexes between Aryl Hydroxamic Acids and Vanadate at Neutral pH

Abstract

Although aryl hydroxamic acids are well-known to form coordination complexes with vanadate (V(V)), the nature of these complexes at neutral pH and submillimolar concentrations, the conditions under which such complexes inhibit various serine amidohydrolases, is not well established. A series of qualitative and quantitative experiments, involving UV/vis, (1)H NMR, and (51)V NMR spectroscopies, established that both 1:1 and 1:2 vanadate/hydroxamate complexes form at pH 7.5, with the former dominating at submillimolar concentrations. Formation constants for the complexes of several aryl and alkyl hydroxamic acids were determined; for example, for benzohydroxamic acid, the stepwise formation constants of the 1:1 and 1:2 complexes were 3000 and 400 M(-1), respectively. The (51)V chemical shift of the 1:1 4-nitrobenzohydroxamic acid complex was -497 ppm, and that of its unsubstituted analogue was -498 ppm. A (1)H-(15)N HSQC spectrum of the 4-nitrobenzo-(15)N-hydroxamic acid/vanadate complex indicated the presence of an N-H group with (15)N and (1)H chemical shifts of 115 and 5.83 ppm, respectively. A (13)C NMR spectrum of the complex of 4-nitrobenzo-(13)C-hydroxamic acid with vanadate displayed a resonance at 170.1 ppm and thus a coordination-induced shift (CIS) of +3.8 ppm. In contrast, the CIS value of an established 1:2 complex, thought to contain chelated hydroxamic acid ligands, was +11.9 ppm. These spectral data led to the following structural picture of 1:1 complexes of vanadate and aryl hydroxamic acids. They contain penta- or hexa-coordinated vanadium. The ligand is in the hydroxamate rather than hydroximate form. The ligand is presumably bound to vanadium through the hydroxamic hydroxyl oxygen, but the hydroxamic acid carbonyl oxygen interacts weakly with vanadium. These species are the most likely candidates for the inhibitors of serine amidohydrolases found in vanadate/hydroxamic acid mixtures.

Investigation on the complex of diperoxovanadate with 2-(2′-pyridyl)-imidazole

“…3 was measured in this work. For the pure 2-(2 0 -Py)-Imi solution, two 14 N peaks appeared at about 295 and 195 ppm, respectively. For the interaction system of NH 4 VO 3 /H 2 O 2 /2-(2 0 -Py)-Imi with 1:5:1 molar ratio (0.2 mol/L vanadate concentration), two 14 N peaks of the coordinated 2-(2 0 -Py)-Imi appeared at about 219 and 157 ppm, which were much more shielded than the free ligand.…”

“…14 N, and 51 V spectra was D 2 O. DSS [3-(trimethylsilyl)-propanesulfonic acid sodium salt] was used as an internal reference for 1 H and 13 C chemical shifts. 14 N and 51 V chemical shifts were measured relatively to the external standard MeNO 2 and VOCl 3 , respectively, with upfield shifts considered negative.…”

“…It is therefore not surprising to see that coordination chemistry and biological mechanism of vanadate compounds have recently encouraged many interests [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. For example, Orvig et al have synthesized and characterized many vanadium (III,IV,V) complexes and studied their insulinomimetic activities [18][19][20][21][22][23][24].…”

“…Kiss et al [11][12][13] have characterized the vanadium (IV,V) complexes in aqueous solution by several spectroscopies. Pratt et al [14][15][16] have investigated the formation and structure of complexes between hydroxamic acids and vanadate at neutral pH and their mechanism of inhibition of the b-lactamase. Among these studies, detailed and thorough spectroscopic investigations on the interaction systems between peroxovanadate complexes and organic ligands have been performed [25][26][27][28][29][30].…”

DFT study of the V(IV)/V(V) oxidation mechanism in the presence of N-hydroxyacetamide

“…The interaction of V(V) and V(IV) with hydroxamic acids is attracting much attention [23][24][25][26][27]. This is due to fact that hydroxamic acids are also biologically very important.…”