An ab initio study of the conformational preferences of Hoechst 33258 in gas-phase and aqueous solution environments

A quantum mechanical study of the conformational preferences of Hoechst 33258, a synthetic minor groove-binding drug, has been performed in both gas-phase and aqueous solution. Gas-phase calculations were performed at the HF/6-31G(d) and MP2/6-31G(d) levels of theory, whereas calculations in the aqueous solution phase were performed using the PCM model with the 6-31G(d) basis set. The molecule was divided into three fragments, which were submitted to a systematic and detailed conformational study. The results clearly indicate that Hoechst 33258 does not adopt a planar conformation in either the gas-phase or aqueous solution. Thus, a folded conformation is not induced by binding of the molecule to DNA, but is an intrinsic property of the compound. Received: 3 March 1998 / Accepted: 29 May 1998 / Published online 19 August 1998