Dehydration-Driven Nanomechanical Responses of the Antiviral Drug EIDD-1931,Crystal Growth & Design

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Dehydration-Driven Nanomechanical Responses of the Antiviral Drug EIDD-1931
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2023-03-10 , DOI: 10.1021/acs.cgd.2c01445
Indira S. Divya _{1,

2} , Amit Mondal ₃ , Surojit Bhunia ₃ , Kiran S. R. N. Mangalampalli ₄ , Jubi John _{1,

2} , C. Malla Reddy ₃ , Sunil Varughese _{1,

2}

Affiliation

The hydrate dimorphs of the antiviral drug EIDD-1931 (EIDD) exist as tautomers possessing different conformations, synthon preferences, thermal decomposition profiles, and mechanical properties. This coexistence of manifold contrasting structural features is unusual and makes the hydrate dimorphs of EIDD-1931 exceptional. As analogs of uridine and cytidine, the tautomers corresponding to the crystal forms (Form I and Form II) of EIDD help effectively block viral RNA replication. With regard to the analogous nucleosides, the computed MESP of EIDD exhibits extensive alterations and disproportionate distribution of maxima and minima sites, contributing to its hydration characteristics. The water of crystallization and its efflorescence have a direct impact on the thermal decomposition profiles as well as the nanomechanical response of the crystal forms because of their distinct roles in the stabilization of the structure─as a two-donor, two-acceptor interaction center occupying isolated sites in Form I as opposed to a one-donor, one-acceptor moiety confined to a void-filling role in Form II. From a broader perspective, the nanomechanical responses correlated to the interaction characteristics, and dehydration events are remarkable in deriving a molecular basis of the properties in pharmaceutics wherein a major share of the pharmaceuticals exists as hydrates.

中文翻译：

抗病毒药物 EIDD-1931 的脱水驱动纳米机械反应

抗病毒药物 EIDD-1931 (EIDD) 的水合物二晶型物作为互变异构体存在，具有不同的构象、合成子偏好、热分解曲线和机械性能。这种多种对比结构特征的共存是不寻常的，并且使 EIDD-1931 的水合物二晶型物与众不同。作为尿苷和胞苷的类似物，EIDD的晶型（Form I和Form II）对应的互变异构体有助于有效阻断病毒RNA的复制。关于类似的核苷，EIDD 的计算 MESP 表现出广泛的改变和最大和最小位点的不成比例分布，有助于其水合特性。结晶水及其风化对热分解曲线以及晶体形式的纳米力学响应有直接影响，因为它们在稳定结构方面具有独特的作用──作为占据双供体、双受体相互作用中心形式 I 中的孤立位点与形式 II 中局限于空隙填充作用的单供体、单受体部分相反。从更广泛的角度来看，与相互作用特征相关的纳米力学响应和脱水事件在推导药物特性的分子基础方面非常显着，其中大部分药物以水合物形式存在。双受体相互作用中心占据形式 I 中的孤立位点，而不是单供体，单受体部分局限于形式 II 中的空隙填充作用。从更广泛的角度来看，与相互作用特征相关的纳米力学响应和脱水事件在推导药物特性的分子基础方面非常显着，其中大部分药物以水合物形式存在。双受体相互作用中心占据形式 I 中的孤立位点，而不是单供体，单受体部分局限于形式 II 中的空隙填充作用。从更广泛的角度来看，与相互作用特征相关的纳米力学响应和脱水事件在推导药物特性的分子基础方面非常显着，其中大部分药物以水合物形式存在。

更新日期：2023-03-10

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