Hydrogen bonded and stacked geometries of the temozolomide dimer.

Dispersion-corrected density functional theory (DFT) and MP2 quantum chemical methods are used to examine homodimers of temozolomide (TMZ). Of the 12 dimer configurations found to be minima, the antarafacial stacked dimer is the most favored, it is lower in energy than coplanar dimers which are stabilized by H-bonds. The comparison between B3LYP and B3LYP-D binding energies points to dispersion as a primary factor in stabilizing the stacked geometries. CO(π) → CO(π*) charge transfers between amide groups in the global minimum are identified by NBO, as well as a pair of weak CH∙∙N H-bonds. AIM analysis of the electron density provides an alternative description which includes N∙∙O, N∙∙N, and C∙∙C noncovalent bonds.