Synthesis, characterisation and insulin-mimetic activity of oxovanadium(IV) complexes with amidrazone derivatives

Abstract The complexation of VO 2+ ion by ten acetamidrazone and 2-phenylacetamidrazone derivatives (L) was studied. Sixteen novel VO 2+ complexes were synthesised and characterised through the combined application of analytical and spectroscopic (EPR (electron paramagnetic resonance), FT-IR and diffuse reflectance electronic absorption) techniques. Eight are 1:2 species of composition [VOL 2 ]SO 4  ·  x H 2 O and eight are 1:1 species with formula [VOL(SO 4 )] n  ·  x H 2 O. The experimental data suggest a bidentate coordination mode for L with the donor set formed by the imine nitrogen and the carbonyl oxygen. EPR spectra indicate a square-pyramidal geometry for the 1:1 complexes and a penta-coordinated geometry intermediate between the square-pyramid and the trigonal-bipyramid for the 1:2 species. The hyperfine coupling constant along z axis, A z , of the 1:2 complexes exhibits a marked reduction with respect to the predicted value (∼148 × 10 −4  cm −1 vs. ∼170 × 10 −4  cm −1 ). IR spectroscopic evidence supports the presence of sulphate as a counter-ion in the 1:2, and as a bridging bidentate ligand in the 1:1 complexes. Insulin-mimetic tests on modified fibroblasts, based on a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide) assay, performed on three of the bis-chelated and eight of the mono-chelated derivatives, indicate that they are biologically active. The similar hydro/lipophilicity and the lack of ligand substituents recognizable by cell membrane receptors prevent substantial differentiation in the insulin-mimetic action.