Binary Complexes of Oxovanadium (IV) with Vitamin B6 Compounds and Glycinehydroxamate

Several oxovanadium (IV) complexes of pyradoxamine (PM), pyridoxol (P), pyridoxal (PL), and glycinehydroxamate (GX) were obtained as a result of potentiometric data analysis using SUPERQUAD at I = 0.15 M NaCl and T = 25°C. Protonated, unprotonated and hydroxospecies were detected in solutions. No polymeric species of oxovanadium(IV) were found under the experimental conditions used. Differential pulse polarography (DPP) was used to study the reduction properties of VO 2+ complex species. Electronic spectra of the systems were discussed. Structures of some complex species of the vanadyl ions were suggested based on the knowledge of the ligating atoms provided by the ligands as well as the assumption that the metal ion can acquire at least an octahedral geometry. The uptake of these species in biological systems was also discussed. INTRODUCTION Vanadium is an essential trace element for different organisms. Our body contains about 23 mg of vanadium distributed in many parts of the body and some of it is stored in fat tissues [1]. Many reports reveal that different vanadium compounds reduce cholestrol levels in humans [2]. These compounds may also help in treating atherosclerosis and heart disease [3]. Other reports have shown that some vanadium compounds exhibit antitumoral effect [4,5]. It has also been found that vanadium compounds reduce the growth of human prostate cancer cells in tissue cultures, and also lower the bone and liver cancer in animals [3]. One of the most important physiological response of vanadium is its insulinmimetic property [6-9]. Vanadium compounds enhance glucose transport and oxidation. They also increase glycogen synthesis in liver and inhibit gluconeogenesis [10]. It is also known that vanadium is required as an essential cofactor in certain haloperoxidases and nitrogenases of some red and brown algae [11]. On the other hand, vanadate compounds even at low concentration, inhibit certain enzymes such as ion transport ATP-ase, phosphatase and ribonuclease [12]. Although the uptake of vanadium in humans is about 10-60 μg/day, yet its essentiality as an ultratrace element has not been proven [13]. To avoid complexity of biochemical processes, chemists usually deal with model systems in order to understand the behaviour of chemical species in solutions. These models allow chemists to establish a relationship between structural, equilibrium, and kinetic features of well defined chemical systems and to apply the results to a more complicated biological systems. *Address correspondence to this author at the Chemistry Department, Kuwait University P.O. Box 5969 Safat, 13060, Kuwait; E-mail: [email protected] Most of vanadium compounds that have insulin-mimetic properties have vanadium in the oxidation state (IV). Examples of these are: vanadyle sulfate [6], bis(pyrrolidine-Ncarbodithioato)oxovanadium(IV) [14], bis(cysteine methylester)-oxovanadium(IV), [15],bis(acetylacetonato)oxovanadium(IV) [16], bis-(picolinato)oxovanadium(IV), [5]. Although clinical tests of oral administration of vanadate compounds reduces blood sugar, yet this process is associated with toxic symptoms such as weight loss, poor appetite, vomiting and diarrhea. Continuous effort is devoted to prepare vanadium compounds of high potency for blood sugar and less toxicity [17]. Although the mechanism that describes the role of vanadium compounds as therapeutic agents in reducing blood sugar is not clear, yet its inhibiting ability on the protein tyrosine phosphatases can not be neglected [18]. The main goal of this investigation is to understand the chemical properties and behaviour of oxovanadium(IV) complexes involving low molecular weight biological ligands in solutions and to apply such knowledge in future to relevant biological systems. The selected ligands were vitamin B6 compounds and glycinehydroxamate which have no reported toxic characters compared to other used ligands. EXPERIMENTAL Materials Reagent grade glycinehydroxamate, pyridoxamine dihydrochloride, pyridoxol hydrochloride, and pyridoxal hydrochloride were Sigma chemicals (>98%). They were used without further purification. Highly pure VOSO4 (Aldrich) was used in this work. Preparation of Solutions A stock solution of VO 2+ (0.02M) and glycinehydroxamate(0.02M) were prepared in identical concentration of Binary Complexes of Oxovanadium (IV) with Vitamin B6 Compounds The Open Inorganic Chemistry Journal, 2009, Volume 3 57 HCl. The stock solutions of the vitamin B6 ligands were freshly prepared before titrations. The stock solutions of the ligands were stored at ~4 o C. The stock solution of VO 2+ was standardized by complexometric EDTA titration using CuYPAN or dithizone as an indicator. The appropriate concentration of the ligands and metal ions (1.0 – 3.0) x10 3 M were prepared, keeping the ionic strength of solution constant at I = 0.15 M NaCl in a 25.0 ml measuring flasks. The determination of binary formation constants of vanadium metal ion with vitamin B6 compounds, pyridoxamine (PM), pyridoxol (P), and pyridoxal (PL), and glycinehydroxamate (GX) was achieved by potentiometric titrimetry. Potentiometric titrations were carried out by Metrohm Titrator, model 670 Titroprocessor, equipped with Metrohm glass and calomel electrodes. The pH meter was calibrated by three standard buffers (4.00, 7.00, 10.00) as well as by titrating standard HCl solution (0.10 M) against standard NaOH, carbonate free (0.097 M) at I = 0.15 M NaCl and at T = (25 ±0.01) o C. The calculated pH values were different from the measured values by only ~ 0.016 pH unit. This was attributed to the glass junction-potential and the activity coefficient of the H + ions. The prepared solutions of different systems were transferred to a titration cell thermostated at (25 ± 0.01) 0 C by using Julabo circulator. Highly purified nitrogen gas is purged through the titrated solution before and during titration. Titration with 0.097 M NaOH carbonate free at ionic strength of 0.15 M NaCl was done till pH ~11. Although the equilibration time was found to be less than 5 seconds yet the pH readings were taken after 40 seconds by adjusting the titrator time to a 40 s time interval after each addition of the titrant. The data is then collected by an online personal computer. Spectrophotometric Analysis A Cary 500 spectrophotometer was used to collect the spectral data for GX-V(IV), PMV(IV), PL-V(IV) and P-V(IV) systems. Solutions of VO 2+ (1.0 – 3.0)10 4 M and the ligands (1.0 – 3.0)10 -3 M in 100 ml volumetric flask at the ionic strength of 0.15 M NaCl were prepared. The pH of solutions were adjusted by the addition of small amount of NaOH or HCl as appropriate. Polarographic measurements were done by using Metrohm Polarecord E 506. The polarograph was provided with a dropping mercury indicator electrode, saturated Ag/AgCl reference electrode and a counter platinum-wire electrode. The settings of the polarographs were as follows: the voltage range varied, depending on the system under consideration, between 0.0 and – 2.0 volt. The pulse amplitude was 40 mV, the drop time was one second, the recorder speed was 0.5 mm/s. The experiment was performed at room temperature (~ 23 0 C). The pH values were in the range of 2.0 to 11.0 and were obtained by a Radiometer pH meter type 84 provided with a Russell combination electrode (calibrated as previously mentioned). The concentrations of the ligands were each 5.0x10 -3 M and that of VO 2+ was 1.0x10 -3 M. All solutions were deoxygenated by purging with pure humidified nitrogen gas through them before taking the differential pulse polarograms (DPP) and above the surface during the run. RESULTS AND DISCUSSION Equilibrium Study Table 1 shows the sets of solutions used in the potentiometric titrations of VO 2+ and that of the ligands: pyridoxol (P), pyridoxal (PL), pyridoxamine (PM) and glycinehydroxamate (GX). The precipitation pH’s are only noticed in case of PL-V(IV), and PM-V(IV) systems at pH > 5.0. The inflection points in the graphs of pH vs a, Fig. 1(a, b, c, and d), (where a is the number of moles of base per total number of moles of hydrogen ions; both from the ligands and added acid) indicated complex formation of different stoichiometries. The pH vs a graphs shifts to the left in all systems as the ligand: metal ratios (at constant metal ion concentration) increases. This may be attributed to the absence of higher complex species of the form 3:1: rH + (r = number of hydrogen ions). Several equilibrium models were tested by using SUPERQUAD program [19], keeping invariant the protonation constants of the ligands. The best set of formation constants was determined by selecting the model resulted from obtaining the best values of the statistical parameters provided by the program, Table 2. In addition, the model which gave calculated pH identical to the experimental pH was accepted as shown in the distribution curves of different complex species as a function of pH, Figs. 2(a, b, c, and d) and /or correlating the calculated and experimental titrration volume obtained from the adopted equilibrium model, Figs. 3(a, b, c, and d). In both cases HYSS2003 program was used [20]. Table 1. Concentration in Molarity of the Reactants Used in the pH-Metric Study at Ionic Strength of 0.15 M NaCl and T= 25 o C VO 2+ x10 3 M GX x10 3 M PM x10 3 M P x10 3 M PL x10 3 M 1.0 2.0 0.8 1.0 1.5 0.8 1.0 1.0 2.0 1.6 2.0 3.0 2.4 3.0 1.0 2.0 1.6 2.0 3.0 2.4 3.0 1.0 2.0 1.6 2.0 3.0 2.4 3.0 1.0 2.0 1.6 2.0 3.0 2.4 3.0 Duplicate runs were done for each experiment. 58 The Open Inorganic Chemistry Journal, 2009, Volume 3 Marafie et al.