Ab initio and DFT studies on the structure, infrared spectrum, and thermodynamic properties of Hoechst 33258

Ab initio and DFT(B3LYP) levels of theory, with basis sets of 3-21G, 6-31G*, and LanL2DZ, have been applied to the specific DNA binder Hoechst 33258. All calculations lead to a structure with two benzimidazole groups and one phenyl group being coplanar. Atoms H-33 and H-37 bear large positive charges, and the distance between the two atoms is about 5 angstrom, which allows the molecule interacting with the negative sites of neighboring bases in the DNA helix and thus facilitates Hoechst 33258 to gravitate on AT-rich regions in the minor groove of DNA, owing to the deeper negative potential in such sequences. The most stable conformer corresponds to the dihedral angles of ca. 0 degrees for phi(1-2-14-15) and phi(27-26-5-4), and 180 degrees for phi(20-19-11-12). This fact provides clear evidence that Hoechst 33258 has an arc-like shape with coplanar aromatic rings. Both the HOMO and the LUMO are made up of the P-z orbitals of the non-hydrogen atoms in two benzimidazole groups and one phenyl group. On going from the ground state to the first singlet excited state, the lengths of the single bonds between the aromatic rings decrease, and the aromatic rings are more conjugated with each other in the excited state. The beat of formation (Delta H-f) of Hoechst 33258, evaluated from the isodesmic reaction, is 406.32 kJ/mol at the B3LYP/6-31G* level.