Biospeciation and antidiabetic effects of oxidovanadium(IV) complexes

• Main Author: Ugirinema, Vital
• Other Authors: Tshentu, Zenixole R
• Format: Others
• Language: English
• Published: Nelson Mandela Metropolitan University 2014
• Subjects: Vanadium compounds; Diabetes
• Online Access: http://hdl.handle.net/10948/d1020973

The syntheses of bis(1R-imidazole-2/4-carboxylato)oxidovanadium(IV) complexes was successfully carried out and the complexes were isolated in the solid state. The coordinated water was confirmed by elemental analyses, and single crystal XRD. The complexes were therefore distorted octahedral rather than square planar due to the coordination of water at the sixth position. The reaction of the vanadyl ion (VO2+) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), and phosphate (Phos)] and high molecular weight (HMM) human serum proteins [albumin (HSA) and transferrin (hTf)] were studied in aqueous solution using potentiometric acid base titrations under oxygen and carbon dioxide–free conditions. The data obtained from these titrations was used to calculate the binary and ternary stability constants using the programme HYPERQUAD. The overall stability constants for VO2+-L-Ox system (log β1111 = 18.9, 18.79 and 19.86), VO2+-L-Lact system (log β1111 = 21.83, 20.98 and 22.86), and VO2+-L-Phos system (log β1111 = 27.35, 24.16 and 27.42) (for L= Im4COOH, Im2COOH and MeIm2COOH, respectively) were obtained. The species distribution diagrams showed that under physiological pH the following ternary and quaternary species; [(VO)L(bL)], and [VO(L)(bL)(OH)], would dominate provided that the competition with serum proteins is not too strong. These species were also confirmed by HPLC, LC-MS and EPR. The overall stability constants for the VO2+-L-HSA system (log β2,1,1,0 = 24.3, 23.7 and 24.7), and for the VO2+-L-hTf system (log β2,2,1,0 = 31.1, 30.8, 36.4 for L = Im4COOH, Im2COOH and MeIm2COOH, respectively), suggesting stronger binding of transferrin. The formation constants for the formation of binary (VO(IV) and the proteins) were 9.1 and 13 for log β11, and 20.9 and 25.2 for β12, for human serum albumin and human serum transferrin respectively. The species distribution diagrams for the proteins (HMM) with oxidovanadium(IV) under physiological pH was dominated by VO(HMM)2, VOL(HMM) for unsubstituted Im4COOH and Im2COOH, however, for the N-substituted MeIm2COOH, the species distribution diagrams under physiological pH, were dominated by VOL2, VO(HMM)2 and VO2L2(HMM). These species were further confirmed by HPLC, MALDI-TOF-MS and EPR. The glucose stimulated insulin secretion (GSIS) action of the complexes was investigated using INS-1E cells at 1μM concentration which was established through cytotoxicity studies via the MTT assay. The vanadium salt (VOSO4), cationic vanadium(IV) complex ([VO(MeImCH2OH)2]2+) were also included in the GSIS study in addition to the three neutral complexes [VO(Im4COO)2, VO(Im2COO)2 and VO(MeIm2COO)2] for comparison. The neutral complexes, especially VO(MeIm2COO)2, showed promising results in the stimulation of insulin secretion than the cationic complex and the vanadium salt.