Prabhakar Prathiksha, Ramalingam Anantharaj
Department of Chemical Engineering, Sri Sivasubramaniya Nadar College of Engineering, Rajiv Gandhi Salai (OMR), Kalavakkam, Chennai, Tamil Nadu, 603110, India.
J Mol Model. 2025 Sep 2;31(9):263. doi: 10.1007/s00894-025-06474-w.
The drug solubilization is still a significant challenge in pharmaceutical research. This study examined the sigma-surface, sigma-profile, and sigma potential of 35 water insoluble drugs using deep eutectic solvents (DES) made up of a strong hydrogen bond acceptor (HBA) choline chloride (ChCl) and several hydrogen bond donors (HBDs) at the molecular level. The combinations of ChCl and 75 HBDs include acid (C1-C10), alcohol (C1-C10), aldehyde (C1-C10), amide (C1-C10), amine (C1-C10), ester (C2-C10), ether (C2-C10), and ketone (C3-C10). Analysis showed that the presence of HBD and HBA in the drugs has an impact on solubility, as ChCl has shown better interaction with drugs that contain the donor groups such as carboxyl (-COOH), amino (-NH₂), and hydroxyl (-OH) due to their strong hydrogen-bonding ability, high polarity, and large hydrogen-bond networks. These results show that acid, alcohol, and amide-based DESs can be potential carriers for poorly soluble drugs and the necessity of understanding their physiochemical characteristics to maximize solubility.
COSMOthermX (Version: 19.0.5) and TURBOMOLE (TmoleX21.0.1) were utilized to gather and process the data presented here. Turbomole was used for COSMO simulations to evaluate solvation effects at various levels and characteristics as input for the COSMOtherm software. Geometry optimizations were performed using density functional theory (DFT) at the BP86 (Becke-Perdew) functional level with the triple zeta valence polarization (TZVP) basis set. COSMO files were created using the BP_TZVP_19.ctd parameterization in COSMOthermX (version 19.0.5).
药物增溶仍是药物研究中的一项重大挑战。本研究在分子水平上研究了由强氢键受体（HBA）氯化胆碱（ChCl）和几种氢键供体（HBD）组成的深共熔溶剂（DES）对35种水不溶性药物的西格玛表面、西格玛分布和西格玛电位的影响。ChCl与75种HBD的组合包括酸（C1 - C10）、醇（C1 - C10）、醛（C1 - C10）、酰胺（C1 - C10）、胺（C1 - C10）、酯（C2 - C10）、醚（C2 - C10）和酮（C3 - C10）。分析表明，药物中HBD和HBA的存在对溶解度有影响，因为ChCl与含有供体基团如羧基（-COOH）、氨基（-NH₂）和羟基（-OH）的药物表现出更好的相互作用，这归因于它们强的氢键形成能力、高极性和大的氢键网络。这些结果表明，基于酸、醇和酰胺的DESs可以成为难溶性药物的潜在载体，并且有必要了解它们的物理化学特性以实现最大溶解度。
使用COSMOthermX（版本：19.0.5）和TURBOMOLE（TmoleX21.0.1）来收集和处理此处呈现的数据。Turbomole用于COSMO模拟，以评估不同水平和特征的溶剂化效应，作为COSMOtherm软件的输入。使用密度泛函理论（DFT）在BP86（Becke - Perdew）泛函水平和三重ζ价极化（TZVP）基组下进行几何优化。使用COSMOthermX（版本19.0.5）中的BP_TZVP_19.ctd参数化创建COSMO文件。
