Karimi Narges, Heydari Dokoohaki Maryam, Zolghadr Amin Reza, Klein Axel
Department of Chemistry, School of Science, Shiraz University, Shiraz 71946-84795, Iran.
University of Cologne, Faculty for Mathematics and Natural Sciences, Department of Chemistry and Biochemistry, Institute for Inorganic Chemistry and Materials Chemistry, Köln, Germany.
Phys Chem Chem Phys. 2025 Jul 23;27(29):15527-15543. doi: 10.1039/d5cp01312g.
Molecular dynamics (MD) simulation and density functional theory (DFT) analyses were carried out on the solubilization of the heteroaromatic drugs allopurinol, losartan, and omeprazole in reline, which is a deep eutectic solvent (DES) composed of choline chloride/urea in 1 : 2 molar ratio. The aim was to gain a deep understanding of the molecular properties of the different components in the solutions and the dynamic interactions between them. Especially, the impact of hydrogen bonding and π-stacking interactions between rings planes in drug⋯drug interactions leading to unwanted aggregations was carefully evaluated using combined angular/radial distribution functions and also natural bond orbital theory. Addition of the drugs to the DES led to decreased conductivity and diffusion coefficients (ranging from 1.52 to 1.07 × 10 m s). The effects of the small allopurinol on the DES structure are more pronounced compared with the larger losartan and omeprazole molecules. This is in line with the formation of aggregates, which are markedly smaller for allopurinol (∼2.6 molecules in average) than for omeprazole (∼4.3) and losartan (∼5.5). DFT-calculated dimers of the drug molecules are stabilized by π-stacking with energies ranging from -10 (allopurinol) to -32 kcal mol (losartan) and show interplanar distances ranging from 0.36 to 0.47 nm. Our observations might pave the way for designing optimized DES for drug delivery.
对异芳族药物别嘌醇、氯沙坦和奥美拉唑在由摩尔比为1:2的氯化胆碱/尿素组成的深共熔溶剂（DES）即reline中的增溶作用进行了分子动力学（MD）模拟和密度泛函理论（DFT）分析。目的是深入了解溶液中不同成分的分子性质以及它们之间的动态相互作用。特别是，使用组合角/径向分布函数以及自然键轨道理论，仔细评估了药物⋯药物相互作用中氢键和环平面间π堆积相互作用对导致不良聚集的影响。将药物添加到DES中会导致电导率和扩散系数降低（范围为1.52至1.07×10 m s）。与较大的氯沙坦和奥美拉唑分子相比，小分子别嘌醇对DES结构的影响更为明显。这与聚集体的形成一致，别嘌醇的聚集体（平均约2.6个分子）明显小于奥美拉唑（约4.3个）和氯沙坦（约5.5个）。DFT计算的药物分子二聚体通过π堆积稳定，能量范围为-10（别嘌醇）至-32 kcal mol（氯沙坦），平面间距离范围为0.36至0.47 nm。我们的观察结果可能为设计用于药物递送的优化DES铺平道路。
