Solid-state NMR and computational investigation of solvent molecule arrangement and dynamics in isostructural solvates of droperidol

Abstract

Citation for published item:frzi § sD eF nd rodgkinsonD F @PHISA 9olidEstte xw nd omputtionl investigtion of solvent moleule rrngement nd dynmis in isostruturl solvtes of droperidolF9D olid stte nuler mgneti resonneFD TS F ppF IPEPHF Further information on publisher's website: httpXGGdxFdoiForgGIHFIHITGjFssnmrFPHIRFHWFHHI Publisher's copyright statement: NOTICE: this is the author's version of a work that was accepted for publication in Solid State Nuclear Magnetic Resonance. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reected in this document. Changes may have been made to this work since it was submitted for publication. A denitive version was subsequently published in Solid State Nuclear Magnetic Resonance, 65, February 2015, 10.1016/j.ssnmr.2014.001. Additional information:Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. 2 H NMR spectra of deuterium-labelled samples allowed the characterization of the solvent molecule dynamics in the alcohol solvates and the non-stoichiometric hydrate. The likely motion of the alcohol molecules is rapid libration within a site, plus occasional exchange into an equivalent site related by the inversion symmetry, while the water molecules are more strongly disordered. DFT calculations strongly suggest that the differences in dynamics between the solvates are related to differences in the energetic penalty for reversing the orientation of a solvent molecule.Keywords: droperidol; solid-state NMR; hydrates/solvates; isostructural solvates; solvent dynamics; spin-lattice relaxation; motional broadening; ab initio calculations Graphical abstract Highlights 15 N CP/MAS NMR clearly distinguishes ordered and dynamically disordered systems.  Spectral quality is strongly correlated to ABMS broadenings.  2 H MAS NMR provides direct insight into the nature of the solvent motion.  DFT calculations help to rationalise the differences in experimental observations.

Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid

“…Indeed, since we are comparing the same group (C=O) with similar limited mobility, we can safely suppose nearly equal cross-polarization rates (i.e., T IS ) and 1 H T 1ρ values. Similar, the approach was successfully tested for other systems [50]. The position of the C=O C4 signal, at higher frequencies in PZQ-AA (166.8 ppm) and PZQ-2P (165.7 ppm) with respect to that of PZQ Form B (164.3) may be taken as evidence of their involvement in intermolecular hydrogen bonding with the solvent molecules [51].…”

NMR crystallography of molecular organics

“…the value of Z' = 0.5 inferred from 13 C NMR similarly significantly constrained the number of space groups to be considered [326]. The value of Z' is not always evident from 13 C spectra; DFT calculations are helpful in these cases to confirm that symmetry independent sites have locally very similar environments [157,327].…”

“…The presence of disorder often introduces effective additional symmetry. For example, in a set of essentially isomorphous solvates of droperidol, Z' could be either 1 or 2 depending on whether the solvent was disordered (creating a pseudo-inversion centre) or not [327]. In practice, however, strong susceptibility broadenings meant that 13 C NMR spectra could not clearly distinguish between ordered vs. disordered solvent arrangements.…”

Synergy of Solid-State NMR, Single-Crystal X-ray Diffraction, and Crystal Structure Prediction Methods: A Case Study of Teriflunomide (TFM)

“…The transformation from TFM LT and TFM RT appears to be driven by an entropic preference similar to that in a previous study. 100 It is curious to compare the case here for TFM , where disorder in TFM RT is associated with a change in comparison to TFM LT in the Z′ value from 2 to 1, with that presented by Szell et al, where disorder leads to a change in Z′ value from 1 to 2. 101 …”