NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

Abstract

Publisher's copyright statement: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-pro t 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. ABSTRACT Solid-state NMR is used to characterise dynamics in the ethanol solvate of the pharmaceutical material formoterol fumarate and its associated desolvate. Jump rates and activation barriers for dynamic processes such as phenyl ring rotation and methyl group rotational diffusion are derived from 1D-EXSY and 13 C spin-lattice relaxation times respectively. 2 H and 13 C spin-lattice relaxation times measured under magic-angle spinning conditions are used to show that the fumarate ion in the desolvate is undergoing smallamplitude motion on a frequency scale of 100s of MHz at ambient temperature with an activation parameter of about 32 kJ mol -1 . Exact calculations of relaxation times under MAS provide a simple and robust means to test motional models in cases where relaxation rate maxima are observed, including for systems where the crystal structure of the material is unknown.

Deuterium MAS NMR Studies of Dynamics on Multiple Timescales: Histidine and Oxalic Acid

“…The T 1Z and T 1Q values averaged over the spinning sidebands are given in Table 3 and Table 4. Based on the previous relation, we can therefore estimate a correlation time of free diffusion between 0.2 ns at [61] analysed the 2 H T 1Z relaxation under MAS and remarked that the relaxation data were not very sensitive to the motional model. The COOD and D 2 O sites in oxalic acid show a trend similar to ND 3 + in l-histidine, namely a decrease of the T 1Z as temperature is raised.…”

“…Assuming the same geometry for ND 3 + and assuming that we are in the extreme narrowing limit, the absence of any significant anisotropy of T 1Z indicates that the NÀ 2 H bond diffuses freely about the CÀN axis. Based on the previous relation, we can therefore estimate a correlation time of free diffusion between 0.2 ns at [61] analysed the 2 H T 1Z relaxation under MAS and remarked that the relaxation data were not very sensitive to the motional model. The relaxation rate of quadrupolar order, which is dominated by motions at the Larmor frequency, remains constant for the two ND sites of the imidazole ring in l-histidine, regardless of temperature.…”

Bisoprolol and Bisoprolol-Valsartan Compatibility Studied by Differential Scanning Calorimetry, Nuclear Magnetic Resonance and X-Ray Powder Diffractometry

“…Ref. ( 52 ) and references therein. Carbon C-8 and C-12 exhibit similar behavior, although this is not clearly resolved due to overlap with the C-7 resonance.…”

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

“…there is no single motional process creating a well-defined T 1 minimum. We have previously observed small amplitude motions that are large enough to drive relaxation but too small to significantly average the quadrupolar coupling constant [30]. The crystal structure solution and the averaged chemical environments for the droperidol molecules in the unit cell indicate that the solvent molecules are also flipping orientations, but the 2 H NMR data and the 13 C relaxation times are not sensitive to this process.…”