Enantioselective binding of chiral 1,14-dimethyl[5] helicene-spermine ligands with B- and Z-DNA

Duplex DNA adopts a right-handed B-DNA conformation under physiological conditions. Z-DNA, meanwhile, has a left-handed helical structure and is in equilibrium with right-handed B-DNA. We recently reported that the bisnaphthyl maleimide-spermine conjugate (1) induced a B-to Z-DNA transition with high efficiency at low salt concentrations. It was also found that the bisnaphthyl ligand (1) spontaneously transformed into the corresponding [5] helicene derivative (2). Because [5] helicene 2 can potentially be chiral and because the chiral discrimination of B-and Z-DNA is also of interest, we became interested in whether enatiomerically pure [5] helicene-spermine conjugates might discriminate the chirality of B-or Z-DNA. In this study, we have demonstrated an efficient synthesis of chiral DNA-binding ligands by the conjugation of a [5] helicene unit with a spermine unit. These chiral helicene ligands exhibited recognition of B-and Z-DNA, with (P)-3 displaying preference for B-DNA and (M)-3 for Z-DNA. The characteristic features of the helicene-spermine ligands developed in this study include two points: the cationic spermine portion produces electrostatic interactions along the phosphate backbone of the minor groove, and the helicene forms complexes in an end-stacking mode. Such binding modes, together with the thermodynamic parameters, account for the mode of chiral recognition of (P)- and (M)-3 for B-and Z-DNA. (c) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.