Platinum(IV) Complexes with Dipeptide. X-ray Crystal Structure, 195Pt NMR Spectra, and Their Inhibitory Glucose Metabolism Activity in C andida a lbicans

Three dipeptide complexes of the form K[PtIV(dipep)Cl3] and two complexes of the form K[PtIV(Hdipep)Cl4] were newly prepared and isolated. The platinum(IV) complexes containing the dipeptide were obtained directly by adding KI to H2[PtCl6] solution. The reaction using KI was rapidly completed and provided analytically pure yellow products in the form of K[Pt(dipeptide)Cl3] for H2digly, H2glyα-ala, H2α-alagly and H2diα-ala. The K[PtIV(digly)Cl3] complex crystallizes in the monoclinic space group P21/c with unit cell dimensions a = 10.540(3) Å, b = 13.835(3) Å, c = 8.123(3) Å, β = 97.01(2)°, Z = 4. The crystal data represented the first report of a Pt(IV) complex with a deprotonated peptide, and this complex has the rare iminol type diglycine(2−) coordinating to Pt(IV) with the bond lengths of the C2−N1 (amide) bond (1.285(13) Å). The 195Pt NMR peaks of the K[PtIV(dipep)Cl3] and the K[PtIV(Hdipep)Cl4] complexes appeared at about 270 ppm and at about −130 ppm, respectively, and were predicted for a given set of ligand atoms. While the K[PtIV(x-gly)Cl3] complexes, where x denotes the glycine or α-alanine moieties, were easily reduced to the corresponding platinum(II) complexes, the K[PtIV(x-α-ala)Cl3] complexes were not reduced, but the Cl- ion was substituted for OH- ion in the reaction solution. The K[Pt(digly)Cl3] and K[Pt(gly-l-α-ala)Cl3] 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 inhibited by K[Pt(digly)Cl3] and K[Pt(gly-l-α-ala)Cl3] but not by the antifungal agent fluconazole.