Regarding the diamagnetic components in Rosenberg's 'platinum pyrimidine blues': Species in the cis-Pt(NH3)(2)-1-methyluracil system

摘要

Antitumor-active "Pt-pyrimidine blues", derived from cis-(NH3)(2)Pt-II and the pyrimidine model nucleobase 1-methyluracil (1MeUH) upon reaction in a 1:1-ratio in water, represent mixtures of predominantly (ca. 95%) 1:1-, 1:2-, 2:2-, 2:1- complexes (Pt:1MeU(H)) and unreacted 1MeUH, as well as a minor proportion (estimated 5%) of oligomeric species, some of which become partially oxidized to provide the blue color. The present study concentrates on the identification of (at least) seven colorless or yellow diamagnetic components by use of H-1 NMR spectroscopic methods (H-1, H-1-COSY; DOSY) and/or by comparison with isolated authentic samples, respectively. These are cis-[Pt(NH3)(2)(1MeU-N3)(OH2)](+) (1b), cis-Pt(NH3)(2)(1MeU-N3)(2) (1c), head-tail- and head-head isomers of cis-[(NH3)(2)Pt(1MeU-N3,O4)(2)Pt(NH3)(2)](2+) (3a) and (3b), respectively, cis-[(NH3)(2)Pt(mu-OH)(mu-1MeU-N3,O4)Pt(NH3)(2)](2+) (10), cis-[(NH3)(2)(1MeU-N3)Pt (mu-OH)Pt(1MeU-N3)(NH3)(2)](+) (4), and unreacted 1MeUH. A likely eights component, cis-[(NH3)(2)(1MeU-N3)Pt(mu-OH)Pt(OH/OH2)(NH3)(2)](+/2+) (9) has not been identified unambiguously. The propensities of Pt-II to form mu-hydroxido species and of N3-platinated 1MeU to attract a second Pt-II via its O4 site are responsible for the formation of these species. The as yet unidentified minor, presumably oligomeric species most likely represent compounds with terminal 1MeU-N3 ligands, as well as bridging 1MeU-N3,O4 and/or bridging OH- ligands, formed upon co-condensation reactions of primary products with available cis-[Pt(NH3)(2)(OH2)(2)](2+). Earlier ideas, that "Pt-pyrimidine blues" may largely or even exclusively be oligomers with a uniform motif involving exclusively bridging pyrimidine ligands, are not substantiated by our study.