Accurate fragment-based 51-V chemical shift predictions in molecular crystals

Abstract

Nuclear magnetic resonance (NMR) spectroscopy plays a crucial role in determining molecular structure for complex biological and pharmaceutical compounds. NMR investigations are increasingly reliant on computation for mapping spectral features to chemical structures. Here we benchmark the accuracy of fragment-based 51V chemical shielding tensor calculations using a training set comprised of 10 biologically and pharmaceutically relevant oxovanadium complexes. Using our self-consistent reproduction of the Madelung potential (SCRMP) electrostatic embedding model, we demonstrate comparable performance between fragment methods and computationally demanding cluster-based techniques. Specifically, fragment methods employing hybrid density functionals are capable of reproducing the experimental 51V isotropic chemical shifts with a training set rms error of ~9 ​ppm, representing a 20% improvement over traditional plane wave techniques. We provide training set-derived linear regression models for mapping the absolute shieldings obtained from computation to the experimentally determined chemical shifts using four common density functionals; PBE0, B3LYP, PBE, and BLYP. Finally, we establish the utility of fragment methods and the reported regression parameters examining four oxovanadium structures excluded from the training set including the tetracoordinate oxovanadium silicate (Ph3SiO)3VO, VO15NGlySalbz which contains redox-active ligands, and the solid-state form of the common 51V NMR reference compound VOCl3.