H. Buning et al., Bis[platinum(II)] and bis[platinum(IV)] complexes with optically active bis(vicinal-1,2-diamines) and their interaction with DNA, J INORG BIO, 75(4), 1999, pp. 269-279
Bis[platinum(II)] [Cl2Pt(LL)PtCl2] complexes 2, 5 and 8 with chiral non-rac
emic ligands: 1a-c (LL=(R,R), (S,S) and (R,S) N,N'-bis( (3,4-diaminobutyl)h
exanediamide); 4a,b (LL = (R,R) and (S,S) N,N'-bis[3,4-bis(diaminobutyl)] u
rea); 7a-d (LL' = (R,R), (S,S), (R,S) and (S,R) 4,5-diamino-N-(3,4-diaminob
utyl) pentanamide) and bis[platinum(IV)] complex 10-13 with ligands: 1a,b a
nd 4a,b have been prepared and characterized by IR, H-1, C-13 and Pt-195 NM
R spectra. The interactions of 2a-c, 5a, 5b, 8a-d and 10a with dsDNA were i
nvestigated with the goal of examining whether the chirality, the nature of
the spacer and the oxidation state have an influence on platinum-DNA bindi
ng properties. Pill the bis[platinum(II)] complexes form with dsDNA intra-
and interstrand crosslinks and crosslinks over sticky ends, whereas the bis
[platinum(IV)] complex 10a only forms intra- and interstrand crosslinks. Th
e platinum-DNA coordination sites were determined by the T4 DNA polymerase
footprinting method. The results show that all investigated bis(platinum) c
omplexes have high preference: towards distinct purines. All isomeric bis(
amide) 2a-c and mono( amide) 8a-d complexes exhibit nearly the same binding
pattern, whereas the ureide complexes 5a and 5b have other coordination si
tes with higher sequence preference. Interestingly. the ureides 5a and 5b d
iffer in their coordination sites not only in comparison to the bis(amides)
2a-c and mono( amides) 8a-d, but also between each other. The bis[platinum
(IV)] complex 10a also differs in coordination sites in comparison to all t
he bis[platinum(II)] compounds. (C) 1999 Elsevier Science Inc. All rights r
eserved.