Hydrates of active pharmaceutical ingredients: A 35Cl and 2H solid-state NMR and DFT study

Assessment of Approximations to the Embedding Potential in Frozen-Density Embedding Theory for the Calculation of Electric Field Gradients

“…The three components on the diagonal, by convention, are referred to as | V x x | ≤ | V y y | ≤ | V z z | A number of metrics can be used to evaluate the quality of an EFG calculation, including consideration of all three independent components of the EFG tensor. Experiments related to the EFG are only sensitive to V zz and, as has been done in other recent reports, , we will only consider V zz in our analyses and not the other, smaller elements.…”

“…15,16 The need for explicit quantum mechanical treatment of the electrons in the molecule is thus commonly recognized in the community; therefore, several nonembedding quantum mechanical approaches have been used by various researchers. One method models only the nearest atoms in the system and neglects the environment completely, 4 another targets only the shift in the largest diagonal component of the EFG relative to a reference calculation, 17 and other approaches are based on the error compensation ansatz. 18,19 In this work, we turn to the explicit quantummechanical treatment of the embedded species and embedding methods based on frozen-density embedding theory (FDET), in which the embedding potential (multiplicative embedding operator) is given as a sum of the classical electrostatic component and the nonclassical part representing the quantum confinement by means of a universal bifunctional.…”

“…The Sternheimer approximation is computationally advantageous and has been used effectively in simulations of EFG dynamics, − but its usefulness is limited due to the dependence of the empirical coefficients used in relation on the specific system and its geometry. − Additionally, its validity in the condensed phase has been questioned, and the addition of higher-order terms in the electronic response has been proposed. , The need for explicit quantum mechanical treatment of the electrons in the molecule is thus commonly recognized in the community; therefore, several non-embedding quantum mechanical approaches have been used by various researchers. One method models only the nearest atoms in the system and neglects the environment completely, another targets only the shift in the largest diagonal component of the EFG relative to a reference calculation, and other approaches are based on the error compensation ansatz. , In this work, we turn to the explicit quantum-mechanical treatment of the embedded species and embedding methods based on frozen-density embedding theory (FDET), in which the embedding potential (multiplicative embedding operator) is given as a sum of the classical electrostatic component and the nonclassical part representing the quantum confinement by means of a universal bifunctional. − …”

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

“…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.…”