NMR Crystallography: Toward Chemical Shift-Driven Crystal Structure Determination of the β-Lactam Antibiotic Amoxicillin Trihydrate

We report a new strategy for NMR crystallography of multiple-component molecular crystals in which 1 H NMR chemical shifts enter directly in the structure generation step, governed by a genetic algorithm. Chemical shifts are also used in the structure-refinement step as pseudoforces acting on the models, leading to the lowest-energy structure. This methodology, which avoids the use of time-consuming ab initio chemical shift calculations, is successfully applied to powdered amoxicillin trihydrate, a widely used β-lactamic antibiotic.