Blade, Helen, Blundell, Charles D., Brown, Steven P., Carson, Jake, Dannatt, Hugh R., Hughes, Leslie P. and Menakath, Anjali (2020) Data for Conformations in solution and in solid-state polymorphs : correlating experimental and calculated NMR chemical shifts for Tolfenamic Acid. [Dataset]

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Abstract

A new approach for quantitively assessing putative crystal structures with applications in crystal structure prediction (CSP) is introduced that is based upon experimental solution- and magic-angle spinning (MAS) solid-state NMR data and density functional theory (DFT) calculation. For the specific case of tolfenamic acid (TFA), we consider experimental solution-state NMR for a range of solvents, experimental MAS NMR of polymorphs I and II, and DFT calculations for four polymorphs. The change in NMR chemical shift observed in passing from the solution state to the solid state (ΔδExperimental) is calculated as the difference between 1H and 13C experimental solid-state chemical shifts for each polymorphic form (δSolid expt) and the corresponding solution-state NMR chemical shifts (δSolution expt). Separately, we use the gauge-included projector augmented wave (GIPAW) method to calculate the NMR chemical shifts for each form (δSolid calc) and for TFA in solution (δSolution calc), using the dynamic 3D solution conformational ensemble determined from NMR spectroscopy. The calculated change in passing from the solution state to the solid state, ΔδCalculated, is then calculated as the difference of δSolid calc and δSolution calc. Regression analysis for ΔδCalculated against ΔδExperimental followed by a t-test for statistical significance provides a robust quantitative assessment. We show that this assessment clearly identifies the correct polymorph, i.e., when comparing ΔδExperimental based on the experimental MAS NMR chemical shifts of Form I or II with ΔδCalculated based on calculated chemical shifts for polymorphs I, II, III and IV. Complementarity to the established approach of comparing δSolid expt to δSolid calc is explored. We further show that our approach is applicable if there are no solid-state crystal structure data. Specifically, δSolid calc in ΔδCalculated is replaced by the chemical shift for an isolated molecule with a specific conformation. Sampling conformations at specific 15° angle values and comparing them against experimental 13C chemical shift data for Forms I and II identifies matching narrow ranges of conformations, successfully predicting the conformation of tolfenamic acid in each form. This methodology can therefore be used in crystal structure prediction to both reduce the initial conformational search space and also quantitatively assess subsequent putative structures to reliably and unambiguously identify the correct structure.

Item Type:	Dataset
Divisions:	Faculty of Science > Physics
Type of Data:	Experimental data
Publisher:	Department of Physics
Official Date:	23 September 2020
Dates:	Date Event 23 September 2020 Created
Date of first compliant deposit:	23 September 2020
Status:	Not Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Copyright Holders:	University of Warwick
Description:	Data record consists of a zip archive containing raw data, organised into named subfolders according to CASTEP calculations, solid-state NMR data and PXRD analysis, and an accompanying readme file. Raw data files from solid-state NMR experiments includes those for Figure 5A and Supplementary Figures S5 and S6. Raw data files for CASTEP calculations depend on the solid. Calculations of solid (full crystal) include the initial cif file, the geometry optimized cif file and the magres file. Calculations of solid (isolated molecule) include the initial .cell file and the magres file. For the CASTEP calculations of solution conformers of TFA in an isolated box with R1 C7 – R1 N8 – R2 C1 – R2 C6 torsion angle set at 15 degrees intervals , the initial .cell file and the magres file are provided. Raw data files for PXRD analysis are in RAW format.
Related URLs:	https://wrap.warwick.ac.uk/142050 Other
Contributors:	Contribution Name Contributor ID Depositor Brown, Steven P. 1193

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