Multi-component crystals containing urea: mechanochemical synthesis and characterization by ³⁵Cl solid-state NMR spectroscopy and DFT calculations

Abstract

Mechanochemical synthesis provides new pathways for the rational design of multi-component crystals (MCCs) involving anionic or cationic components, which offer molecular-level architectures unavailable to MCCs comprised of strictly neutral components....

Synthesis and Characterization of Xylazine Hydrochloride Polymorphs, Hydrates, and Cocrystals: A 35Cl Solid-State NMR and DFT Study

“…Structural convergence was assessed using a maximum change in energy of 5 × 10 –6 eV atom –1 , a maximum displacement of 5 × 10 –4 Å atom –1 , and a maximum Cartesian force of 10 –2 eV Å –1 . Chlorine magnetic shielding tensors were computed using the GIPAW approach and converted to the chemical shift scale relative to solid NaCl by setting the calculated magnetic shielding of NH 4 Cl to δ iso ( 35 Cl) = 120 ppm . Euler angles, which use the ZY ′ Z ″ convention for rotation, were extracted from the CASTEP output files using EFGShield 4.1 .…”

“…Chlorine magnetic shielding tensors were computed using the GIPAW approach 93 and converted to the chemical shift scale relative to solid NaCl by setting the calculated magnetic shielding of NH 4 Cl to δ iso ( 35 Cl) = 120 ppm. 94 Euler angles, which use the ZY′Z″ convention for rotation, were extracted from the CASTEP output files using EFGShield 4.1. 83 The procedure for calculating 13 C chemical shifts uses both CASTEP and the Amsterdam Modelling Suite (AMS), as described in Supporting S1.…”

“…For example, the calculated values of C Q for the chloride ion in Lhistidine HCl•H 2 O differ by only 120 kHz for DFT-D2* geometry-optimized structural models based on SCXRD structures obtained at 298 and 100 K. However, in rare instances, motions of highly mobile moieties, such as NH 4 + ions, can impact both calculated and experimental EFG tensors; in such cases, these effects can be modeled using ab initio molecular dynamics. 54 The types and arrangements of hydrogen bonds around chloride ions are correlated to the 35 Cl EFG tensors (Table 3). 30,31,36,54,57 Hydrogen bonds with the largest influence on the 35 Cl EFG tensors are those in which the H•••Cl − distance is less than ca.…”

“…54 The types and arrangements of hydrogen bonds around chloride ions are correlated to the 35 Cl EFG tensors (Table 3). 30,31,36,54,57 Hydrogen bonds with the largest influence on the 35 Cl EFG tensors are those in which the H•••Cl − distance is less than ca. 2.2 Å, which we define here as short contacts, whereas all interactions up to ca.…”

“…Our group and others have demonstrated that 35 Cl SSNMR spectroscopy is invaluable for rapid fingerprinting and differentiation of different solid forms of the APIs in both bulk and dosage forms, as well as probing the local geometries of ions, including the types, numbers, and arrangements of chemical species participating in H···Cl – hydrogen bonding. − The 35 Cl SSNMR spectra of chloride ions in organic HCl salts almost always feature broad central-transition (CT, +1/2 ↔ −1/2) powder patterns that are influenced by the second-order quadrupolar interaction (SOQI), and in many cases, chlorine chemical shift anisotropy (CSA). The 35 Cl electric field gradient (EFG) tensor, which gives rise to the QI, is extremely sensitive to changes and/or differences in chloride ion environments that result from distinct hydrogen-bonding arrangements.…”