The application of tailor-made force fields and molecular dynamics for NMR crystallography: a case study of free base cocaine

Abstract

The performance of a fully automatically generated tailor-made force field in the field of NMR crystallography is evaluated and compared with existing benchmarks. The advantages and limitations of NMR crystallography with motional averaging are revealed in this study.

NMR crystallography of molecular organics

“…This would be too large for ab initio DFT, and so snapshots for NMR calculations were derived from a separate simulation on a single unit cell, but which used the average lattice parameters observed in the supercell simulation. In follow-up work, "tailor-made" force fields derived using an automated method from dc-DFT calculations [153] were used to determine vibrational corrections for structures of cocaine generated by crystal structure prediction (see Section 3.8), and to assess whether this provided better discrimination between correct and incorrect structures [154]. While the DFT-derived force fields resulted in objectively more realistic behaviour in MD simulations than the default force field (COMPASS), the vibrational corrections did not significantly improve discrimination.…”

NMR crystallography: structure and properties of materials from solid-state nuclear magnetic resonance observables

“…In the work of Baias, it was noted that while 1 H chemical shifts could be used to identify the correct structure of various small organic molecules produced by CSP methods, 13 C chemical shifts were not as useful or sensitive in this regard, at least in the cases they studied. Interestingly, the study of Li et al (2017) concludes that the influence of motional averaging on the 1 H and 13 C isotropic chemical shifts is minimal, and that the errors inherent to the GIPAW method are actually the limiting factor in obtaining more accurate values. Hofstetter & Emsley (2017) have recently reported on the concept of positional variance in NMR crystallography, providing an 'ORTEP'-style image of positional uncertainties derived from NMR.…”

A jumping crystal predicted with molecular dynamics and analysed with TLS refinement against powder diffraction data

“…A (partial) solution is the introduction of tailor-made force fields (TMFFs): force fields parameterized for one specific chemical compound at a time, allowing for more rigour in the description of the details of the energy potential of that compound (Neumann, 2008). In a previous paper, we described how MD with a tailor-made force field for cocaine describes the room-temperature crystal structure of cocaine very well (Li et al, 2017). The accuracy of these force fields can be further improved by, for example, introducing anisotropic van der Waals interactions for halogens (Day et al, 2005, see section 4.4.2) or replacing the atomic point charges by atomic multipoles (Pyzer-Knapp et al, 2016).…”