Recently, 1H, 31P, and 19F NMR magnetic resonance imaging MRI of radiosensitizers has been applied for measuring tumor and tissue oxygenation. In spite of the great importance of such bioreductive drugs, urthermore, surprisingly little detailed computational work on this subject has appeared. Thus, in this work a detailed computational study of BD is presented, calling special attention to the performance of various theoretical methods in reproducing the 13C and 15N, coupling-constant (H-N) data observed in solution. The most sophisticated approach involves density functional based Car–Parrinello molecular dynamics simulations (CPMD) in aqueous solution and averaging chemical shifts over snapshots from the trajectory. In the NMR calculations for these snapshots (performed at the B3LYP level), a small number of discrete water molecules are retained, and the remaining bulk solution effects are included via a polarizable continuum model (PCM). A similarly good accord with experiment is obtained from much less involved, static geometry optimization and NMR computation of pristine 1 employing a PCM approach. Solvent effects on chemical shift are not due to changes in geometric parameters upon solvation, but arise from the direct response of the electronic wave function to the presence of the solvent, which can be represented by discrete molecules and/or the dielectric bulk.
Keywords: 15N NMR, radiosensitizers, molecular dynamics simulations, solvent effects, spin–spin coupling constants.