Thermodynamic Stability Considerations for Isostructural Dehydrates

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

“…This confirms that the acetonitrile breaks the local symmetry of droperidol molecules, consistent with the determined crystal structure [20]. The experimental and GIPAW-calculated 15 N chemical shift differences are almost the same, 1.0 and 0.8 ppm respectively. The alcohol molecules are strongly hydrogen-bonded with the droperidol O1 atom, thus affecting the strength of the intermolecular hydrogen bond between droperidol molecules N2-H···O1 and the calculated chemical shift difference for N2 is significantly higher in S Me and S Et , 1.6 and 3.2 ppm respectively.…”

“…15 N spectra were recorded at ambient temperature, whereas 13 C and 2 H spectra were recorded at controlled temperatures from 20 o C down to -45 o C. Note that these are set temperatures that do not attempt to correct for sample heating under magicangle spinning; these are estimated to be of the order of +5, +8 and +15 °C for the 2 H, 15 N and 13 C spectra respectively. 13 C and 15 N spectra were obtained under MAS conditions using cross polarization (CP) with the following conditions: recycle delay 7-30 s for NSH, S Me and S Et , and 120-180 s for S ACN , and S NM , contact time 0.5-2 ms, a sample spin rate of 13 kHz for 13 15 N by setting the high-frequency signal from a replacement sample of adamantane to 38.4 ppm or the nitrate signal from a replacement sample of solid ammonium nitrate to -5.1 ppm, and typically processed with an apodisation function corresponding to a 20 Hz Lorentzian line-broadening prior to Fourier transformation. 13 C linewidths were determined by fitting the peaks to a mixed Lorentzian /Gaussian lineshape in the Bruker TopSpin software.…”

“…It is also possible to form mixed isostructural solvates, where solvent molecules can be exchanged in only a subset of the crystallographic sites [13; 14]. Although empty host structures can be stable [15], they are typically unstable [16] or collapse immediately after the removal of the guest, despite the weak nature of the host-guest interactions [17].…”

“…In this study we use 13 C, 15 N and 2 H solid-state NMR to determine and characterize the differences between these five droperidol isostructural solvates. This includes the identification and characterization of the molecular motion in NSH, S Me and S Et , to explain the slight disorder of water molecule in NSH and to distinguish between static vs. dynamic disorder in the alcohol solvates.…”

“…Solvate characterisation using 15 N CPMAS spectra Figure 4. 15 N CPMAS spectra of droperidol solvates S Et , S Me and S ACN , showing the splitting of the N2 peak in the spectrum of S ACN .…”