Structural characterization and comparative analysis of two crystalline forms of drug cocrystal (S086) by MicroED, XPS, and XAFS

IF 2.4 3区化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR

Polyhedron Pub Date : 2025-02-19 DOI:10.1016/j.poly.2025.117451

Wen-Jie Xu , Jie Yan , Song Li , Duan-Ming Tan , Sheng Hu

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Abstract

Similar to the world’s first marketed ARNI drug sacubitril/valsartan (LCZ696), S086 is also a drug-drug cocrystal formed by neprilysin inhibitor (NEP) and angiotensin receptor blocker (ARB). ARNI drugs have played an important role in treating hypertension as a new class of antihypertensive drugs. Therefore, understanding the solid-state structure of S086 has become very meaningful. Employing advanced analytical techniques such as MicroED, XPS and XAFS, our comprehensive analysis has elucidated that the two crystalline forms, α and ξ of S086, are cocrystals derived from the synergistic combination of EXP3174, sacubitril, and calcium atoms, mediated by strong interactions. Due to the difficulty in obtaining X-ray single crystal structures, XPS and XAFS analyses, which offer unique insights into material structure, reasonably suggest that the two crystal forms of S086 possess highly similar coordination structures centered around calcium atoms with mixed ligands, but there are still subtle differences. The subtle differences in carboxylate coordination modes between α and ξ are reflected in the recently published linear and nonlinear IR spectroscopic studies of S086.

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来源期刊

Polyhedron 化学-晶体学

CiteScore

4.90

自引率

7.70%

发文量

515

审稿时长

2 months

期刊介绍： Polyhedron publishes original, fundamental, experimental and theoretical work of the highest quality in all the major areas of inorganic chemistry. This includes synthetic chemistry, coordination chemistry, organometallic chemistry, bioinorganic chemistry, and solid-state and materials chemistry. Papers should be significant pieces of work, and all new compounds must be appropriately characterized. The inclusion of single-crystal X-ray structural data is strongly encouraged, but papers reporting only the X-ray structure determination of a single compound will usually not be considered. Papers on solid-state or materials chemistry will be expected to have a significant molecular chemistry component (such as the synthesis and characterization of the molecular precursors and/or a systematic study of the use of different precursors or reaction conditions) or demonstrate a cutting-edge application (for example inorganic materials for energy applications). Papers dealing only with stability constants are not considered.