NOESY investigation of bicalutamide conformational changes in DMSO: Role of solution concentration in polymorph formation

被引：0

作者：

Belov, Konstantin V. ^{[1
]}

Khodov, Ilya A. ^{[1
]}

机构：

[1] G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo

来源：

Journal of Molecular Liquids | 2025年 / 422卷

基金：

俄罗斯科学基金会;

关键词：

Bicalutamide; Conformers; Drugs; NMR; NOESY; Spatial structure;

D O I：

10.1016/j.molliq.2025.126896

中图分类号：

学科分类号：

摘要：

Conformationally polymorphism refers to the phenomenon where the formation of different solid forms of a compound is predominantly governed by the molecular conformation in solution. This study explores the conformational behavior of bicalutamide (BCL), a nonsteroidal antiandrogen with low aqueous solubility, which influences its nucleation pathway and polymorph formation. Bicalutamide exists in two distinct conformations, «open» (Form I) and «closed» (Form II), which are concentration-dependent and determined by intra- and intermolecular interactions. These conformational differences affect the nucleation process, packing efficiency, and stability of the polymorphs, impacting the solubility, stability, and bioavailability of the compound. Using NMR spectroscopy and quantum-chemical calculations, the distribution of «open» and «closed» BCL conformers was studied at various concentrations in dimethyl sulfoxide (DMSO‑d6). Results show a shift in the conformer population from predominantly «closed» at high concentrations to predominantly «open» at lower concentrations, with a sharp transition observed in the concentration range of 1.44 M to 1.08 M. This concentration-induced conformational rearrangement influences the nucleation pathways and polymorph formation, critical for pharmaceutical applications, as different polymorphs exhibit variations in physicochemical properties. © 2025 Elsevier B.V.

引用

共 58 条

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