MER-[RU(TERPY)CL-3] (TERPY=2,2'/6',2''-TERPYRIDINE) SHOWS BIOLOGICAL ACTIVITY, FORMS INTERSTRAND CROSS-LINKS IN DNA AND BINDS TWO GUANINE DERIVATIVES IN A TRANS CONFIGURATION

摘要

The compound mer-[Ru(terpy)Cl-3] was found to be active as a cytostatic in L1210 leukemia cells, with an activity in between cisplatin and carboplatin. It was shown that the Ru complex covalently binds to DNA and this binding results in the formation of similar to 2% interstrand cross-links. In addition, no Ru-promoted nicks are formed. The parent compound has also been reacted with the DNA model bases 9-methylhypoxanthine (9mhyp) and 9-ethylguanine (9egua). The solid complexes trans-[Ru(terpy)(B- kN(7))(2)(H2O)](PF6)(2), where B = 9mhyp or 9egua, were isolated and characterized in acetone solution by proton NMR. The bases are symmetrically arranged around the metal center, and involved in hydrogen bonding with the water ligand, most likely via their O6 atoms. The water ligand has been substituted by acetonitrile. The complexes trans-[Ru(terpy)(B-kN(7))(2)(CH3CN)](PF6)(2), where B = 9mhyp or 9egua, have been prepared in situ. Compared to the aqua complexes, the hydrogen bond donor molecule is lost and a rearrangement of the guanine bases is observed. [References: 33]