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oai:figshare.com:article/33851308 2026-09-16T13:45:48Z portal_1197 item_type_3 month_year_09_2026

Data for Exploring the potential of multinuclear solid‐state 1H, 13C, and 35Cl magnetic resonance to characterize static and dynamic disorder in pharmaceutical hydrochlorides Patrick M.J. Szell (24985393) Zainab Rehman (11644291) Ben P. Tatman (11816330) Leslie P. Hughes (1357650) Helen Blade (1600069) Steven P. Brown (1296819) Crystallography Nuclear magnetic resonance spectroscopy Pharmaceutical chemistry X-ray crystallography Organic compounds Density functionals Migrated from ePrints Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch to batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field 35Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: Specifically, dynamic disorder occurring in duloxetine hydrochloride (1), static disorder in promethazine hydrochloride (2), and trifluoperazine dihydrochloride (3). In all structures, the presence of crystallographic disorder was confirmed by 13C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3, 1H MAS NMR provided additional confirmation. Applying 35Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3, while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from 1H, 13C, and 35Cl NMR, we show that 3 exhibits a unique case of disorder involving the +N-H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy 3 distinct sites.<br><br>Dataset contains following items: DFT-calculated data Solid-state NMR Data 2022-10-05T00:00:00Z Dataset Dataset 10.82444/warw.33851308.v1 https://figshare.com/articles/dataset/Data_for_Exploring_the_potential_of_multinuclear_solid_state_1H_13C_and_35Cl_magnetic_resonance_to_characterize_static_and_dynamic_disorder_in_pharmaceutical_hydrochlorides/33851308 CC BY 4.0