Interest in the mechanism of action of the anticancer drag cis-diammedichloroplatinum(II) (cisplatin) has greatly stimulated the study of the interaction of cisplatin and its analogs with DNA fragments. Circular dichroism (CD) data were obtained on complexes of the type (R,R-DACH)PtG2 and (S,S-DACH)PtG2 (DACH = 1,2-diaminocyclohexane; G = 9-EtG, 3'GMP. In general these systems give rise, in solution, to an equilibrium mixture of three rotamers (HH, LHT and DHT) with either right handed (R) or left handed (L) canting. The configuration of the carrier ligand can significantly influence the stabilization of one rotamer over the others. R,R-DACH and S,S-DACH ligands stabilize L and R canting, respectively. For each type of canting one rotamer ensures better dipole-dipole interaction (LHT and DHT for L and R canting, respectively). In addition to the carrier ligand effect, phosphate cis-G interaction (3'GMP and 5'GMP) and phosphate cis-amine interaction (5'GMP) also influence rotamer distributions. These latter effects are pH dependent. The different interactions have been considered in the interpretation of CD spectra at various pH values.
Rotamer distribution and base canting in [Pt(DACH)G2] complexes as revealed by CD spectra
BENEDETTI, MICHELE;
2001-01-01
Abstract
Interest in the mechanism of action of the anticancer drag cis-diammedichloroplatinum(II) (cisplatin) has greatly stimulated the study of the interaction of cisplatin and its analogs with DNA fragments. Circular dichroism (CD) data were obtained on complexes of the type (R,R-DACH)PtG2 and (S,S-DACH)PtG2 (DACH = 1,2-diaminocyclohexane; G = 9-EtG, 3'GMP. In general these systems give rise, in solution, to an equilibrium mixture of three rotamers (HH, LHT and DHT) with either right handed (R) or left handed (L) canting. The configuration of the carrier ligand can significantly influence the stabilization of one rotamer over the others. R,R-DACH and S,S-DACH ligands stabilize L and R canting, respectively. For each type of canting one rotamer ensures better dipole-dipole interaction (LHT and DHT for L and R canting, respectively). In addition to the carrier ligand effect, phosphate cis-G interaction (3'GMP and 5'GMP) and phosphate cis-amine interaction (5'GMP) also influence rotamer distributions. These latter effects are pH dependent. The different interactions have been considered in the interpretation of CD spectra at various pH values.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
