SEQUENCE-SELECTIVE DNA RECOGNITION AND PHOTOCLEAVAGE - A COMPARISON OF ENANTIOMERS OF RH(EN)(2)PHI(3+)

The recognition and photoinduced cleavage of DNA by the enantiomers of bis(ethylenediamine)(9,10-phenanthrenequinone diimine)Rh(III) [Rh(en) (2)phi(3+)] have been characterized and the basis for enantioselective differences delineated. Rh(en)(2)phi(3+) isomers bind strongly to DNA via intercalation and, upon photoactivation with near-UV light, produ ce direct strand cleavage. On the basis of product analysis, the photo induced DNA cleavage appears to proceed by a mechanism consistent with that observed for the parent Rh(phen)(2)phi(3+), involving direct abs traction of the 3'-hydrogen atom of the deoxyribose by the activated, intercalated phi. Quantitative photocleavage, titrations indicate tigh t binding by both enantiomers to the DNA duplex. For Delta-Rh(en)(2)ph i(3+), DNA site affinities range from 0.3 x 10(6) to 8.0 x 10(6) M(-1) , and a distinct preference for GC sites is evident. Lambda-Rh(en)(2)p hi(3+) is found to be sequence neutral with an average site affinity o f 2 x 10(6) M(-1). The basis for sequence selectivity of the enantiome rs has been examined through comparison of photocleavage patterns to t hose of several phi complexes of rhodium(III) containing or lacking ax ial amines; those complexes containing the axial amines are found to t arget GC sites. DNA photocleavage studies on oligonucleotides containi ng the modified bases O-6-methylguanine, 7-deazaguanine, and deoxyurac il have been utilized to determine points of interaction on the DNA he lix. These results establish binding by both complexes in the major gr oove of DNA. Differences in site recognition between enantiomers are a ttributed to the different hydrogen bonding and van der Waals contacts available in the major groove for the ancillary ethylenediamine ligan ds which differ in disposition in the two isomers.