MP2 and DFT Calculations of the Interaction Energies Between Boronated Aromatic Molecules and Small DNA Models: Applications to Cancer Therapy

Abstract

Boronated molecules are increasingly used in pharmacological applications, including cancer therapy. In boron-neutron capture therapy, boronated molecules localized in tumor cells are bombarded with slow neutrons in order to induce cell death. This work examines possible localization of boronated molecules in DNA by examining differences in interaction energies between boronated and non-boronated ligands with nucleic acid models. We have created complexes of boronated and non-boronated aromatic ligands with different nucleic acid sequences and optimized their structures. Counterpoise-corrected interaction energies for these single- and double-stranded complexes have been calculated using MP2, CCSD, and various DFT functionals with the 6-31+G* and 6-311+G* basis sets. Results show consistent differences in binding between boronated molecules and non-boronated molecules to nucleic acids within single-stranded DNA complexes. ONIOM(MP2:AM1) interaction energy calculations for boronated and non-boronated ligands within double-stranded DNA complexes largely agree with the single-stranded results. Double-stranded complexes were also modeled with and without charges on the phosphate groups and produced similar results. Interactions energies of a model hybrid intercalant possessing a dipole indicate improved interactions with charged, double-stranded complexes. The use of boron in intercalating drug design shows promise in enhancing the interaction strength and selectivity of DNA-targeted drugs.