DNA recognition by the enantiomers of Rh(en)2phi3+ : recognition through hydrogen bonding and van der Waals contacts

Citation

Shields, Thomas P. (1995) DNA recognition by the enantiomers of Rh(en)2phi3+ : recognition through hydrogen bonding and van der Waals contacts. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/tx6p-mg53. https://resolver.caltech.edu/CaltechETD:etd-10222007-131939

Abstract

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The enantiomers of Rh(en)2phi[...] (en = ethylene diamine, phi = 9,10-phenanthrene quinone diimine) have been prepared in order to explore systematically the contributions of hydrogen bonding and van der Waals contacts to sequence selective DNA binding. Both enantiomers bind strongly to DNA via intercalation of the aromatic phi ligand, and produce direct strand scission upon irradiation with near-UV light. The cleavage mechanism is consistent with the direct abstraction of the C3'-H atom from the major groove of DNA by a bound, photoexcited Rh(phi)[...] species. Elements of the sequence specificity of [...] and [...] were established by comparing recognition characteristics to those of several [...] complexes containing ancillary saturated amines and a thioether, and by cleavage of oligonucleotide targets containing [...], 7-deazaguanine and deoxyuracil substitutions. Both enantiomers display a strong sensitivity to the inclusion or removal of a single methyl group in the major groove of [...] displays relatively high selectivity in targeting [...] steps and this selectivity is the result of hydrogen bonding between the axial amines of the metal complex and the [...] position of guanine residues. In contrast, [...] is less selective; besides binding to [...] steps, the A-enantiomer also recognizes [...] steps through a positive van der Waals contact between the ancillary methylene groups and the 5-methyl group of thymine. The structural basis for these enantioselective elements of recognition have also been investigated via [...] methods. Both [...] bind to d(GTGCAC)[...] by classical intercalation, and 2D-NOESY studies of the [...] complex demonstrate specific intercalation at the central [...] site. Molecular models show that deep intercalation of the phi ligand ideally locates the ancillary ethylene diamine ligands for the proposed hydrogen bonding and van der Waals contacts. While illustrating the importance of hydrogen bonding and van der Waals contacts in achieving site specificity, the current work also suggests a modular approach to the design of molecules capable of recognizing larger DNA sequences.

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