Synthesis and Characterization of V^IVO Complexes of Picolinate and Pyrazine Derivatives. Behavior in the Solid State and Aqueous Solution and Biotransformation in the Presence of Blood Plasma Proteins

Abstract

Oxidovanadium(IV) complexes with 5-cyanopyridine-2-carboxylic acid (HpicCN), 3,5-difluoropyridine-2-carboxylic acid (HpicFF), 3-hydroxypyridine-2-carboxylic acid (H2hypic), and pyrazine-2-carboxylic acid (Hprz) have been synthesized and characterized in the solid state and aqueous solution through elemental analysis, IR and EPR spectroscopy, potentiometric titrations, and DFT simulations. The crystal structures of the complexes (OC-6-23)-[VO(picCN)2(H2O)]·2H2O (1·2H2O), (OC-6-24)-[VO(picCN)2(H2O)]·4H2O (2·4H2O), (OC-6-24)-Na[VO(Hhypic)3]·H2O (4), and two enantiomers of (OC-6-24)-[VO(prz)2(H2O)] (Λ-5 and Δ-5) have been determined also by X-ray crystallography. 1 presents the first crystallographic evidence for the formation of a OC-6-23 isomer for bis(picolinato) V(IV)O complexes, whereas 2, 4, and 5 possess the more common OC-6-24 arrangement. The strength order of the ligands is H2hypic ≫ HpicCN > Hprz > HpicFF, and this results in a different behavior at pH 7.40. In organic and aqueous solution the three isomers OC-6-23, OC-6-24, and OC-6-42 are formed, and this is confirmed by DFT simulations. In all the systems with apo-transferrin (VO)2(apo-hTf) is the main species in solution, with the hydrolytic V(IV)O species becoming more important with lowering the strength of the ligand. In the systems with albumin, (VO)(x)HSA (x = 5, 6) coexists with VOL2(HSA) and VOL(HSA)(H2O) when L = picCN, prz, with [VO(Hhypic)(hypic)](-), [VO(hypic)2](2-), and [(VO)4(μ-hypic)4(H2O)4] when H2hypic is studied, and with the hydrolytic V(IV)O species when HpicFF is examined. Finally, the consequence of the hydrolysis on the binding of V(IV)O(2+) to the blood proteins, the possible uptake of V species by the cells, and the possible relationship with the insulin-enhancing activity are discussed.

Behavior of the potential antitumor VIVO complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies

“…The chemical form with which a vanadium compound reaches the target organs affects the uptake by the cells, which can take place through passive diffusion or be mediated by transport proteins. It was shown that the geometry at the physiological pH of a pharmacologically active VOL 2 compound, where L is a bidentate ligand, can influence the interaction with the proteins, such as transferrin (hTf), albumin (HSA), immunoglobulin G (IgG) or hemoglobin (Hb) [39]: when it is cis-octahedral (cis-VOL 2 (H 2 O)), the equatorial water molecule can be replaced by an accessible His-N to form a species with stoichiometry cis-VOL 2 (Protein), whereas when it is square pyramidal (VOL 2 ) no interaction is expected [37,38,[40][41][42][43][44][45][46][47][48][49][50] …”

Bis(picolinato) complexes of vanadium and zinc as potential antidiabetic agents: synthesis, structural elucidation and in vitro insulin-mimetic activity study

“…Oxidovanadium(IV), V IV O, compounds 1 and 2 were synthesized from VOSO 4 Á5H 2 O and HpicFF or H 2 hypic as described previously. 18 Dioxidovanadate(V) and V V O 2 , compounds were prepared from ammonium metavanadate and the corresponding picolinic acid analogues, HpicFF (3) or H 2 hypic (4), in a 1 : 2 ratio in methanol or water/methanol, respectively. Zinc(II) bis(3,5-difluoropicolinato) and bis(3-hydroxypicolinato) complexes were prepared in two steps.…”

“…25 Lately, we have been studying V IV O compounds with picolinic acid and pyrazine derivatives concerning their structures and interactions with serum proteins. 18 For compounds 1 and 2 three isomers were observed by EPR in an organic solvent or in aqueous solution. The H 2 hypic was found to be the strongest ligand and the HpicFF the weakest one and thus different biotransformations at physiological pH in the presence of apo-transferrin and human serum albumin were observed.…”

“…The H 2 hypic was found to be the strongest ligand and the HpicFF the weakest one and thus different biotransformations at physiological pH in the presence of apo-transferrin and human serum albumin were observed. 18 For the study of pharmacological activity all such generated species have to be taken into account and it is a challenge to obtain the observed solution-state species also in the solid state. In this respect, we were able to establish the first crystallographic evidence for the formation of an isomer of a vanadyl bis(picolinato) complex with the two pyridine nitrogen atoms in a mutual trans position previously observed only in the solution-state; the known solid-state structures possess a common arrangement with the two equatorial pyridine nitrogen atoms in a mutual cis position.…”

“…In this respect, we were able to establish the first crystallographic evidence for the formation of an isomer of a vanadyl bis(picolinato) complex with the two pyridine nitrogen atoms in a mutual trans position previously observed only in the solution-state; the known solid-state structures possess a common arrangement with the two equatorial pyridine nitrogen atoms in a mutual cis position. 18 We have extended our research on the diverse structural characteristics and supramolecular topologies of potential antidiabetic vanadium species 23,26 also on vanadium(V) and zinc(II) compounds in order to study the flexibility of the coordination sphere and possible spatial arrangements in these species as well.…”