Platinum(IV) complexes with dipeptide. X-ray crystal Structure,Pt-195 NMR spectra, and their inhibitory glucose metabolism activity in Candida albicans

Three dipeptide complexes of the form K[Pt-IV(dipep)Cl-3] and two complexes of the form K[Pt-IV(Hdipep)Cl-4 were newly prepared and isolated. The plat inum(IV) complexes containing the dipeptide were obtained directly by addin g KI to H2CPtCl6] solution. The reaction using KI was rapidly completed and provided analytically purl yellow products in the form of K[Pt(dipeptide)C l-3] for H(2)digly, H(2)gly alpha -ala, H(2)alpha -alagly and H(2)di alpha -ala. The K[Pt-IV(digly)Cl-3] complex crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions a = 10.540(3) Angstrom ,b = 13.835( 3) Angstrom, c = 8.123(3) Angstrom, beta = 97.01(2)degrees, Z = 4. The crys tal data represented the first report of a Pt(IV) complex with a deprotonat ed peptide, and this complex has the rare iminol type diglycine(2-) coordin ating to Pt(IV) with the bond lengths of the C2-N1 (amide) bond (1.285(13) Angstrom). The Pt-195 NMR peaks of-the K[Pt-IV (dipep)Cl-3 and the K[Pt-IV( Hdipep)Cl-4] complexes appeared at about 270 ppm and at about -130 ppm, res pectively, and were predicted for a given set of ligand atoms. While the K[ Pt-IV(x-gly)Cl-3] complexes, where x denotes the glycine or alpha -alanine moieties, were easily reduced to the corresponding platinum(II) complexes, the K[Pt-IV(x alpha -ala)Cl-3] complexes were not reduced, but the Cl- ion was substituted for OH- ion in the reaction solution. The E([Pt(digly)Cl-3] and K[Pt(gly-L-alpha -ala)Cl-3] complexes inhibited the growth of Candida albicans, and the antifungal activities were 3- to 4-fold higher than those of cisplatin. The metabolism of glucose in C. albicans was strongly inhibi ted by K[Pt(digly)Cl-3] and K[Pt(gly-L-alpha -ala)Cl-3]but not by the antif ungal agent fluconazole.