SYNTHESIS AND ANTIDIABETIC ACTIVITY OF [VO(SALEN)], [VO(SALOPHEN)], [VO(SALCYEN)], AND [VO(ACACEN)] COMPLEXES

• Main Author: Agus Beni Widana, Gede
• Format: Dissertations
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/52187
• Institution: Institut Teknologi Bandung

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by high blood glucose levels, which caused by insufficient amount of insulin or resistance of insulin receptor. DM can lead to other diseases such as skin infections, heart attacks, strokes, kidney failures, and even deaths. Insulin injections can be used to treat DM caused by insulin deficiency, however, to cure the abnormalities of insulin receptors requires a variety of chemical compounds. The oxovanadium(IV) complexes can be used as a drug or food supplement for those who have insulin receptors problems. Some of them use oxovanadium(IV) complexes containing two bidentate ligands with N and O donor atoms. Further research showed that oxovanadium(IV) complexes with tetradentate -ONNO- donor atoms, such as [VO(salen)], are more effective than similar oxovanadium(IV) complexes with two bidentate ligands. The antidiabetic activity of the complex is usually observed using in vitro and in vivo tests. In vitro test using an enzyme that responsible for the metabolism process, while in vivo assays are carried out using alloxan-induced diabetic Wistar rats (Rattus novergicus). In this research, tetradentate -ONNO- ligands have been synthesized by condensation reactions between salicylaldehyde and diimine producing H2salen, H2salophen and H2salcyen ligands, as well asthe condensation reaction between diketone and diimine producing H2acacen ligand. All ligands have been characterized by proton and carbon-13 NMR spectroscopy. The imine groups were observed at chemical shift of 8.44 – 8.87 ppm, while the aromatic groups were observed at ? 6.75 – 7.59 ppm. In the 13C NMR spectra, the imine groups of the four tetradentate ligands were observed at the chemical shift range of 163.19 – 168.34 ppm. Four oxovanadium(IV) complexes have been synthesized, as a result of green solids for [VO(salen)] and [VO(salcyen)], yellowish green for [VO(salophen)] and the dark blue solid for [VO(acacen)]. The chemical formula of [VO(salen)], [VO(salophen)], [VO(salcyen)] and [VO(acacen)]complexes are [VO(C12H18N2O2)],[VO(C20H14N2O2).0,5H2O], [VO(C20H20N2O2)], and [VO(C16H14N2O2)], respectively. All complexes are mononuclear and paramagnetic with ?eff 1.71-1.88 BM refers to one unpaired electron for VO2+. The oxovanadium(IV) complexes are easily dissolved in some organic solvent, such as DMSO, acetonitrile, and dichloromethane. All complexes is found non- ionized in DMSO according to their low molar conductivity value 0.03 - 2.58 ?- 1cm-1mol-1. All solutions (in DMSO) are relatively stable for three days of storage at room temperature.The visible spectra of green solutions of [VO(salen)] and [VO(salcyen)] in DMSO showed ?max 578 – 580 nm, and the yellowish green [VO(salophen)] solution in DMSO showed ?max 597 nm. Two peaks at ?max 559 and 623 nm are observed from [VO(acacen)] solutions in DMSO indicated the Jahn-Teller distortion. The in vitro study showed that the [VO(salen)], [VO(salophen)], [VO(salcyen)] and [VO(acacen)] complexes with a concentration of 250 ?M are capable to inhibit the activity of a human salivary ?-amilase enzyme by 24%, 23%, 35%, and 43%, respectively. The [VO(acacen)] complex is the most potent inhibitor because the acacen ligand contains aliphatic groups as electron-donating group. The electron-donating group in the ligand causes the increase in electron density of the V=O group and strengthen the hydrogen interactions between V=O group and hydroxyl groups on the enzyme, while the three salicylaldimine ligands weaken the hydrogen interactions between V=O group and the enzyme due to aromatics functional groups as an electron-withdrawing group. In vivo antidiabetic assays results showed that the [VO(salen)], [VO(salophen)], [VO(salcyen)], and [VO(acacen)] complexes were able to reduce blood glucose levels of Wistar diabetic rats up to 70% at low doses, which were 0.5 mg vanadium/kgBW. As comparison, metformin, which is commonly used as an antidiabetic drug can reduce blood glucose levels up to 35% at a dose of 50 mg/kg BW. Therefore, the potential of the four oxovanadium(IV) complexes as antidiabetic was significantly higher than metformin.