H‐bonding and stacking interactions between chloroquine and temozolomide

Abstract

The interactions between temozolomide and chloroquine were examined via Dispersion‐Corrected Density Functional Theory and MP2 methods. Chloroquine was considered in both its lowest energy structure and in a local minimum where its aromatic system and secondary amine group are free to interact directly with temozolomide. The accessibility of these two components to intermolecular interaction makes the lowest energy dimer of this local monomer minimum competitive in total energy with that involving chloroquine's most stable monomer geometry. In either case, the most stable heterodimer places the aromatic ring systems of the two molecules parallel and directly above one another in a stacked geometry. Most of the local minima are also characterized by a stacked geometry as well. Comparison between B3LYP and B3LYP‐D binding energies confirms dispersion is a primary factor in stabilizing these structures. © 2016 Wiley Periodicals, Inc.

Interactions between temozolomide and guanine and its S and Se-substituted analogues

“…Negative red sections are located around unprotonated N atoms, as well as the O/S/Se atoms. The corresponding MEP around TMZ was previously reported . This MEP in Figure exhibits primary negative potential around its two O atoms, with positive regions around its H atoms and directly above its six‐membered ring.…”

“…[82,83] For that reason, the molecular electrostatic potentials (MEPs) of the molecules of interest are presented in Figure 4, reported. [29][30][31][32][33][34][35] This MEP in Figure 4 exhibits primary negative potential around its two O atoms, with positive regions around its H atoms and directly above its six-membered ring.…”

“…As a means to focus on certain fundamentals, interactions of TMZ with small molecules have been examined previously by this laboratory, specifically H 2 O, HCl, BH 3 , and . Using the lessons learned, work progressed to larger pharmacological agents chloroquine and quercetin, as well as possible homodimers of TMZ . Progressing toward other aspects of biological activity, the interaction of TMZ with each of the nucleic acid bases was examined and demonstrated the possibility of binding much like the standard Watson‐Crick pairing that is instrumental to the structure and function of DNA .…”

“…[29][30][31] Using the lessons learned, work progressed to larger pharmacological agents chloroquine and quercetin, as well as possible homodimers of TMZ. [32][33][34] Progressing toward other aspects of biological activity, the interaction of TMZ with each of the nucleic acid bases was examined and demonstrated the possibility of binding much like the standard Watson-Crick pairing that is instrumental to the structure and function of DNA. [35] But at the same time, quite different sorts of geometries, energetically similar to or even more stable than such pairing were revealed for the first time.…”

Interactions of Nucleic Acid Bases with Temozolomide. Stacked, Perpendicular, and Coplanar Heterodimers

“…Previous work from this laboratory has examined the interactions of TMZ with both small molecules H 2 O, HCl, BH 3 , and BF 3 , as well as larger pharmacological agents chloroquine and quercetin, as well as possible homodimers of TMZ. [30][31][32][33][34][35] The preferred geometries of the heterodimers of TMZ with both water and HCl are guided by standard H-bond considerations. The O atom of the terminal amide group is the primary atom of attack, with an interaction energy exceeding 30 kJ/mol.…”