Magnetic Resonance in Chemistry

doi: 10.1002/mrc.5103pmid: N/A

doi: 10.1002/mrc.4918pmid: N/A

No abstract is available for this article.

Abraham, Anuji; Salager, Elodie; Krishnan, Damodaran; Su, Yongchao

doi: 10.1002/mrc.5086pmid: 33006157

Lobo, Nitin P.; Ramanathan, K.V.; Narasimhaswamy, T.

doi: 10.1002/mrc.4972pmid: 31770458

In this review, methods to obtain the orientational order of topologically variant molecular mesogens using by one‐ and two‐dimensional (2D) solid‐state 13C nuclear magnetic resonance (NMR) spectroscopy are described. Besides 13C chemical shifts, the 13C─1H dipolar couplings measured from 2D‐separated local field (SLF) technique are used for computing the order parameters of a variety of mesogens. The investigated molecules are composed of a variable number of rings in the core, that is, core ranging from simply one ring to five rings. Among the mesogens investigated, a special focus has been placed on mesogens with thiophene rings, which are gaining popularity as liquid crystalline organic semiconductors. The replacement of a phenyl ring by thiophene in the core has a dramatic influence on molecular topology, as observed from the measured order parameters. The review highlights the advantages of the 2D SLF method for understanding the local dynamics and for mapping the topology of mesogens through the measured order parameters. SLF NMR studies of as many as 24 molecular mesogens that vary in terms of the molecular structure as well as topology are covered in the review. Order parameters of the rings have been estimated from the 13C─1H dipolar couplings in the nematic, smectic A, smectic C, and tilted hexatic phases as well as in B1 and B2 mesophases of various mesogens. It is anticipated that, in the years to come, the 2D SLF method would provide advanced molecular information on structurally complex mesogens that are emerging in liquid crystal science through the incessant efforts of synthetic chemists.

Bai, Shi; Quinn, Caitlin M.; Holmes, Sean T.; Dybowski, Cecil

doi: 10.1002/mrc.4937pmid: 31469449

We report 43Ca and 13C solid‐state nuclear magnetic resonance (NMR) spectroscopic studies of the ethylene glycol solvate of atorvastatin calcium. The 13C and 43Ca chemical shift and 43Ca quadrupolar coupling tensor parameters are reported. The results are interpreted in terms of the reported X‐ray diffraction crystal structure of the solvate and are compared with the NMR parameters of atorvastatin calcium trihydrate, the active pharmaceutical ingredient in Lipitor®. Hartree–Fock and density functional theory calculations of the NMR parameters based on a cluster model derived from the optimized X‐ray diffraction crystal structure of the ethylene glycol solvate of atorvastatin calcium are in reasonable agreement with the experimental 43Ca and 13C NMR measurables.

Mathew, Renny; Uchman, Karolina A.; Gkoura, Lydia; Pickard, Chris J.; Baias, Maria

doi: 10.1002/mrc.4987pmid: 31900955

A combined experimental and computational approach was used to distinguish between different polymorphs of the pharmaceutical drug aspirin. This method involves the use of ab initio random structure searching (AIRSS), a density functional theory (DFT)‐based crystal structure prediction method for the high‐accuracy prediction of polymorphic structures, with DFT calculations of nuclear magnetic resonance (NMR) parameters and solid‐state NMR experiments at natural abundance. AIRSS was used to predict the crystal structures of form‐I and form‐II of aspirin. The root‐mean‐square deviation between experimental and calculated 1H chemical shifts was used to identify form‐I as the polymorph present in the experimental sample, the selection being successful despite the large similarities between the molecular environments in the crystals of the two polymorphs.

Corlett, Emily K.; Blade, Helen; Hughes, Leslie P.; Sidebottom, Philip J.; Walker, David; Walton, Richard I.; Brown, Steven P.

doi: 10.1002/mrc.5021pmid: 32187751

Single‐crystal X‐ray diffraction structures of the 5‐amino‐2‐methylpyridinium hydrogen fumarate salt have been solved at 150 and 300 K (CCDC 1952142 and 1952143). A base–acid–base–acid ring is formed through pyridinium‐carboxylate and amine‐carboxylate hydrogen bonds that hold together chains formed from hydrogen‐bonded hydrogen fumarate ions. 1H and 13C chemical shifts as well as 14N shifts that additionally depend on the quadrupolar interaction are determined by experimental magic angle spinning (MAS) solid‐state nuclear magnetic resonance (NMR) and gauge‐including projector‐augmented wave (GIPAW) calculation. Two‐dimensional homonuclear 1H‐1H double‐quantum (DQ) MAS and heteronuclear 1H‐13C and 14N‐1H spectra are presented. Only small differences of up to 0.1 and 0.6 ppm for 1H and 13C are observed between GIPAW calculations starting with the two structures solved at 150 and 300 K (after geometry optimisation of atomic positions, but not unit cell parameters). A comparison of GIPAW‐calculated 1H chemical shifts for isolated molecules and the full crystal structures is indicative of hydrogen bonding strength.

Pugliese, Andrea; Hawarden, Lucy E.; Abraham, Anuji; Tobyn, Michael; Blanc, Frédéric

doi: 10.1002/mrc.4984pmid: 31880823

Hydroxypropylmethylcellulose (HPMC) acetyl succinate (HPMC‐AS) is a key polymer used for the enablement of amorphous solid dispersions (ASDs) in oral solid dosage forms. Choice of the appropriate grade within the material is often made empirically by the manufacturer of small‐scale formulations, followed by extensive real time stability. A key factor in understanding and predicting the performance of an ASD is related to the presence of hydrogen (or other) bonds between the polymer and active pharmaceutical ingredient (API), which will increase stability over the parameters captured by miscibility and predicted by the Gordon–Taylor equation. Solid state nuclear magnetic resonance (NMR) is particularly well equipped to probe spatial proximities, for example, between polymer and API; however, in the case of HPMC‐AS, these interactions have been sometimes difficult to identity as the carbon‐13 NMR spectra assignment is yet to be firmly established. Using feedstock, selectively substituted HPMC polymers, and NMR editing experiments, we propose here a comprehensive understanding of the chemical structure of HPMC‐AS and a definitive spectral assignment of the 13C NMR spectra of this polymer. The NMR data also capture the molar ratios of the acetate and succinate moieties present in HPMC‐AS of various grades without the need for post treatment required by chromatography methods commonly use in pharmacopoeia. This knowledge will allow the prediction and measurement of interactions between polymers and APIs and therefore a rational choice of polymer grade to enhance the solid state stability of ASDs.

Yin, Jinglin; Huang, Chengbin; Guan, Hanxi; Pang, Zhenfeng; Su, Yongchao; Kong, Xueqian

doi: 10.1002/mrc.4982pmid: 31846098

Pharmaceutical amorphous solid dispersions, a multicomponent system prepared by dispersing drug substances into polymeric matrix via thermal and mechanical processes, represent a major platform to deliver the poorly water‐soluble drug. Microscopic properties of drug‐polymer contacts play mechanistic roles in manipulating long‐term physical stability as well as dissolution profiles. Although solid‐state nuclear magnetic resonance has been utilized as an indispensable tool to probe structural details, previous studies are limited to ex situ characterizations. Our work provides likely the first documented example to investigate comelting of ketoconazole and polyacrylic acid, as a model system, in an in situ manner. Their physical mixture is melted and mixed in the solid‐state nuclear magnetic resonance rotor under magic angle spinning at up to approximately 400 K. Critical structural events of molecular miscibility and interaction have been successfully identified. These results design and evaluate the instrumental and experimental protocols for real‐time characterizations of the comelting of pharmaceutical materials.

Carvalho, José P.; Jaworski, Aleksander; Brady, Michael J.; Pell, Andrew J.

doi: 10.1002/mrc.5004pmid: 31997384

A new approach for processing satellite‐transition magic‐angle spinning (STMAS) and multiple‐quantum magic‐angle spinning (MQMAS) data, based on the two‐dimensional one‐pulse (TOP) method, which separates the second‐rank quadrupolar anisotropy and paramagnetic shift interactions via a double shearing transformation, is described. This method is particularly relevant in paramagnetic systems, where substantial inhomogeneous broadening may broaden the lineshapes. Furthermore, it possesses an advantage over the conventional processing of MQMAS and STMAS spectra because it overcomes the limitation on the spectral width in the indirect dimension imposed by rotor synchronization of the sampling interval. This method was applied experimentally to the 27Al solid‐state nuclear magnetic resonance of a series of yttrium aluminum garnets (YAGs) doped with different lanthanide ions, from which the quadrupolar parameters of paramagnetically shifted and bulk unshifted sites were extracted. These parameters were then compared with density functional theory calculations, which permitted a better understanding of the local structure of Ln substituent ions in the YAG lattice.