Platinum(IV) complexes with dipeptide. X-ray crystal structure, 195Pt NMR spectra, and their inhibitory glucose metabolism activity in Candida albicans.
Three dipeptide complexes of the form K[Pt(IV)(dipep)Cl3] and two complexes of the form K[Pt(IV)(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, H2gly(alpha)-ala, H2alpha-alagly and H2di(alpha)-ala. The K[Pt(IV)(digly)Cl3] complex crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions a = 10.540(3) A, b = 13.835(3) A, c = 8.123(3) A, beta = 97.01(2) degrees, 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) A). The 195Pt NMR peaks of the K[Pt(IV)(dipep)Cl3] and the K[Pt(IV)(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[Pt(IV)(x-gly)Cl3] 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)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-alpha-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-alpha-ala)Cl3] but not by the antifungal agent fluconazole.
Watabe
M
M
General Education Department, Kogakuin University, Hachioji, Tokyo 192-0015, Japan. watabe@cc.kogakuin.ac.jp
Kai
M
M
Asanuma
S
S
Yoshikane
M
M
Horiuchi
A
A
Ogasawara
A
A
Watanabe
T
T
Mikami
T
T
Matsumoto
T
T
D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009587:Nitrogen Isotopes; D017671:Platinum Compounds / Q000737:chemistry* / Q000494:pharmacology
D000935:Antifungal Agents; D004151:Dipeptides; D009587:Nitrogen Isotopes; D017671:Platinum Compounds; D005947:Glucose