Sequence-Specific Recognition of DNA by Phenanthrenequinone Diimine Complexes of Rhodium(III): Importance of Steric and van der Waals Interactions

Abstract

The importance of steric and van der Waals interactions in the sequence-specific recognition of DNA by [Rh(phi)]^(3+) complexes has been explored through the synthesis and application of a series of Rh(phi)^(3+) (phi: 9,10-phenanthrenequinone diimine) derivatives. [Rh(phi)]^(3+) complexes intercalate in the major groove of DNA via the phi ligand and promote strand scission in the presence of UV light. The complexes reported here are derivatives of the parent molecules [Rh(phi)_2bpy]^(3+)and [Rh(bpy)_2phi]^(3+)(bpy:2,2'-bipyridyl). The [Rh(phi)]^(3+) complexes have comparable photoefficiencies; therefore, their different photocleavage patterns on ^(32)P-end-labeled DNA fragments reflect their unique sequence-specific recognition characteristics. The shapes of the [Rh(phi)]^(3+) complexes are found to govern DNA recognition and reaction. Importantly and generally, the more sterically bulky complexes, containing methyl or phenyl groups on the ancillary ligands, cleave DNA at a subset of sequences recognized by their parent molecules. [Rh(diphenylbpy)_2phi]^(3+) specifically targets the site 5'-CTCTAGAG-3'. Furthermore, chiral discrimination in site selectivity is observed; the different isomers target different sites. Δ- and Λ-[Rh(5,5'-dimethylbpy)_2phi]^(3+) cleave specifically at sites that are defined by the consensus sequences 5'-C-T-N-G-3' and 5'-A-C/G-T-C/G-3', respectively. The sequence selectivities may be understood on the basis of both negative steric clashes and positive van der Waals interactions between methyl groups on the metal complex and thymine methyl groups in the DNA major groove.

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