Vanadate complexes in serum: a speciation modeling study

Abstract

The speciations of two drug candidate ligands, 2-hydroxypyridine-N-oxide (Hhpno) and 2-mercaptopyridine-N-oxide (Hmpno), with vanadate (V(V)) were determined at 25.0 degrees C and 0.20 mol dm(-3) KCl by pH-metric and (51)V-NMR methods. At pH 7.4, the two predominant compounds with both ligands are the VO(2)L(2) and VO(2)L(OH). NH(4)[VO(2)(hpno)(2)] x 3 H(2)O was prepared in solid form, and its crystal structure was determined by X-ray diffraction. The stabilities of the complexes VO(2)L(2) of five drug candidate ligands were compared at pH 7.4. In view of the stability sequence hpno > maltol approximately hdp (Hhdp: 3-hydroxy-1,2-dimethyl-4-pyridinone) >> mpno > picolinic acid, the first two of these ligands were chosen for equilibrium studies with apotransferrin (apoTf) competition. The V(V)-apoTf stability constants (log K(1) = 6.03 +/- 0.10; log K(2) = 5.46 +/- 0.18) determined by (51)V-NMR spectroscopy were confirmed by ultrafiltration. Both methods proved that there seems to be no hydrogencarbonate-vanadate competition for the apoTf anion-binding positions. The other potential high molecular mass V(V) binder in the serum is human serum albumin (HSA). As no interaction was detected by (51)V-NMR spectroscopy or fluorimetry, the binding properties of HSA were quantified on the basis of literature data. As a final conclusion, speciation modeling calculations suggest that, under serum conditions, apoTf is probably the primary metal ion binder, even in the presence of the most stable V(V) carrier ligands hpno and maltol and HSA plays a negligible role in V(V) binding.

Crystal structure of dicarbonyl(pyridin-2-olate-1-oxido-κ2 O,O′)rhodium(I), C7H4NO4Rh

“…This study forms part of research in our group on the relationships of structure and [6][7][8][9][10][11]. Crystal structures of dicarbonyl rhodium(I) complexes with di erent bidentate ligands have been less studied [12][13][14][15].…”

A novel VIVO–pyrimidinone complex: synthesis, solution speciation and human serum protein binding

“…22,23,40,[43][44][45][46][47][48][49][50] Transferrin (hTF) is a single-chain glycoprotein containing around 630 amino acids which are arranged in two similar lobes, and is important for iron transportation. It is present in human blood plasma in about 37 μM concentration.…”

Development of the application of speciation in chemistry

“…However, X-ray absorption near edge structure (XANES) studies [162] suggest that red blood cells also have an important role in the biospeciation of vanadium. Under these concentration conditions, the carrier ligands, HSA, or small biomolecules present in the serum (lactate, citrate, phosphate, Gly, or His) do not form sufficiently strong complexes to compete with apoTf, although ~5% of the V(V) exists as free H 2 VO 4 -ions in solution [152].…”

“…The V(IV)O [145][146][147][148][149][150][151], V(V) [152,153], and Zn(II) [154] complexes of drug candidate ligands and LMM serum constituents have been studied using several methods in a wide range of conditions, e.g., by pH-potentiometry in the pH range of 2-11, and complete speciation distributions of these multicomponent systems have been reported. The conditional stability constants of the V(V)-apoTf complexes (log  1 = 6.0 and log  2 = 11.4) were determined by 51 V-NMR spectroscopy and ultrafiltration, and no competition was found between V(V) and HCO 3 − for the anion-binding positions of apoTf [152].…”

“…The conditional stability constants of the V(V)-apoTf complexes (log  1 = 6.0 and log  2 = 11.4) were determined by 51 V-NMR spectroscopy and ultrafiltration, and no competition was found between V(V) and HCO 3 − for the anion-binding positions of apoTf [152].…”