Thermal and solvent effects on the NMR and UV parameters of some bioreductive drugs

摘要

~(15)N NMR chemical shifts and n->pi* electronic transition energy for metronidazole(1)has been calculated and compared with experimental data.A detailed computational study of 1 is presented,with special attention to the performance of various theoretical methods for reproducing spectroscopic parameters in solution.The most sophisticated approach involves density functional based on the Car-Parrinello molecular dynamics simulations of 1 in aqueous solution(BP86 level)and averaging chemical shifts and DELTAE(n->pi*)over snapshots from the trajectory.In the NMR and UV 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 good agreement with experiment is also obtained using static geometry optimization and NMR computation of pristine 1 employing a PCM approach.Further theoretical predictions are also reported for ~(17)O NMR and DELTAE(n->pi*)of three hydroxycinnamic acid derivatives,which suggest that it is essential to incorporate the dynamics and solvent effects for NMR and UV calculations in the condensed phase.