ORIGINAL ARTICLE Anastasios J. Tasiopoulos ® Evangelos J. Tolis John M. Tsangaris ® Angelos Evangelou J. Derek Woollins ® Alexandra M.Z. Slawin Joa˜ o Costa Pessoa ® Isabel Correia Themistoklis A. Kabanos Model investigations for vanadium-protein interactions: vanadium(III) compounds with dipeptides and their oxovanadium(IV) analogues Received: 30 July 2001 /Accepted: 8 October 2001 / Published online: 30 November 2001 Ó SBIC 2001 Abstract The reaction of VCl 3 with 1,10-phenanthroline and a series of dipeptides (H 2 dip), having aliphatic as well as aromatic side chains, in methyl alcohol and in the presence of triethylamine affords vanadium(III) com- pounds of the general formula [V III (dip)(MeOH) (phen)]Cl. Aerial oxidation/hydrolysis of the vanadi- um(III) species gives their oxovanadium(IV) analogues of the general formula [V IV O(dip)(phen)]. X-ray crys- tallographic characterization of the [V IV O(dip)(phen)] compounds (where dip 2– =Gly-L-Ala, Gly-L-Val and Gly-L-Phe) revealed that the vanadium atom possesses a severely distorted octahedral coordination and is ligated to a tridentate dip 2– ligand at the N amine atom, the deprotonated N peptide atom and one of the O carboxylate atoms, as well as an oxo group and two phenanthroline nitrogen atoms. Circular dichroism characterization of the V III /V IV O 2+ -dipeptide com- pounds revealed a strong signal for the V IV O 2+ species in the visible range of the spectrum, with a characteristic pattern which may be exploited to identify the N am ,N pep and O car ligation of a peptide or a protein to V IV O 2+ center, and a weak Cotton effect of opposite sign to their vanadium(III) analogues. The visible spectra of the V III - dipeptide compounds revealed two d-d bands with high intensity, thus indicating that the covalency of the metal- donor atoms is significant, i.e. the vanadium d orbitals are significantly mixed with the ligand orbitals, and this is confirmed by the low values of their Racah B pa- rameters. The high-intensity band of the V IV O 2+ -di- peptide compounds at 460 nm implies also a strong covalency of the metal with the equatorial donor atoms and this was supported by the EPR spectra of these compounds. Moreover, the V III /V IV O 2+ -dipeptide complexes were characterized by EPR and IR spec- troscopies as well as conductivity and magnetic suscep- tibility measurements. Keywords Vanadium ® Peptides ® Circular dichroism ® Electron paramagnetic resonance Introduction Vanadium is a bioessential element that is found in remarkably high concentrations in marine ascidians [1], in certain mushrooms [2] and in polychaete worms [3]. In addition, two classes of vanadium enzymes, vanadium nitrogenases [4, 5] and vanadate-dependent haloperox- idases ([6] and references therein), found in Nature, as well as the vanadium’s insulinomimetic action [7, 8, 9, 10, 11, 12] and anticancer activity [13, 14, 15], have spurred a considerable amount of research by bioinor- ganic [16, 17] and coordination chemists [16, 17], bio- chemists, etc. Moreover, the oxovanadium(IV) cation, V IV O 2+ , has been used in electron paramagnetic reso- nance (EPR) as a spin probe [18]. Detailed structural, physicochemical and kinetic investigations on synthetic model compounds of vana- dium with peptides, that are the most closely related models to proteins, will contribute greatly to our J Biol Inorg Chem (2002) 7: 363–374 DOI 10.1007/s00775-001-0308-0 A.J. Tasiopoulos ® E.J. Tolis ® J.M. Tsangaris ® T.A. Kabanos (&) Department of Chemistry, Section of Inorganic and Analytical Chemistry, University of Ioannina, 45110 Ioannina, Greece E-mail: tkampano@cc.uoi.gr Fax: +30-651-44831 A. Evangelou Laboratory of Experimental Physiology, Faculty of Medicine, University of Ioannina, 46110 Ioannina, Greece J.D. Woollins ® A.M.Z. Slawin Department of Chemistry, University of St. Andrews, St. Andrews KY16 9ST, UK J.C. Pessoa (&) ® I. Correia Centro Quı´mica Estrutural, Instituto Superior Te´cnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal E-mail: pcjpessoa@popsrv.ist.utl.pt