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在阴离子型萘普生和布洛芬插入模型细胞膜的过程中,水维持了紫外可见光谱特征。

Water Maintains the UV-Vis Spectral Features During the Insertion of Anionic Naproxen and Ibuprofen into Model Cell Membranes.

作者信息

Rojas-Valencia Natalia, Gómez Sara, Giovannini Tommaso, Cappelli Chiara, Restrepo Albeiro, Núñez Zarur Francisco

机构信息

Facultad de Ciencias Básicas, Universidad de Medellín, Carrera 87 No. 30-65, 050026, Medellín, Colombia.

Scuola Normale Superiore, Classe di Scienze, Piazza dei Cavalieri 7, 56126, Pisa, Italy.

出版信息

J Phys Chem B. 2023 Mar 16;127(10):2146-2155. doi: 10.1021/acs.jpcb.2c08332. Epub 2023 Mar 6.

Abstract

UV-vis spectra of anionic ibuprofen and naproxen in a model lipid bilayer of the cell membrane are investigated using computational techniques in combination with a comparative analysis of drug spectra in purely aqueous environments. The simulations aim at elucidating the intricacies behind the negligible changes in the maximum absorption wavelength in the experimental spectra. A set of configurations of the systems constituted by lipid, water, and drugs or just water and drugs are obtained from classical Molecular Dynamics simulations. UV-vis spectra are computed in the framework of atomistic Quantum Mechanical/Molecular Mechanics (QM/MM) approaches together with Time-Dependent Density Functional Theory (TD-DFT). Our results suggest that the molecular orbitals involved in the electronic transitions are the same, regardless of the chemical environment. A thorough analysis of the contacts between the drug and water molecules reveals that no significant changes in UV-vis spectra are a consequence of ibuprofen and naproxen molecules being permanently microsolvated by water molecules, despite the presence of lipid molecules. Water molecules microsolvate the charged carboxylate group as expected but also microsolvate the aromatic regions of the drugs.

摘要

利用计算技术并结合对纯水环境中药物光谱的比较分析,研究了细胞膜模型脂质双层中阴离子型布洛芬和萘普生的紫外可见光谱。模拟旨在阐明实验光谱中最大吸收波长变化可忽略不计背后的复杂情况。通过经典分子动力学模拟获得了由脂质、水和药物或仅由水和药物组成的系统的一组构型。紫外可见光谱是在原子量子力学/分子力学(QM/MM)方法框架下结合含时密度泛函理论(TD-DFT)计算得到的。我们的结果表明,无论化学环境如何,参与电子跃迁的分子轨道都是相同的。对药物与水分子之间接触的深入分析表明,尽管存在脂质分子,但布洛芬和萘普生分子被水分子永久微溶剂化,这导致紫外可见光谱没有显著变化。水分子如预期那样微溶剂化带电荷的羧基基团,但也微溶剂化药物的芳香区域。

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