Xiangtan Medicine & Health Vocational College, Xiangtan, 411104, China.
School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, 030001, China.
J Mol Model. 2023 Feb 16;29(3):68. doi: 10.1007/s00894-023-05469-9.
Using chemical penetration enhancers to improve the penetration effect is one kind of important strategies in transdermal drug delivery system. Azone is a widely used transdermal absorption enhancer for transdermal drug delivery. To shed light on the permeation-promoting mechanism of azone, we selected ternary systems formed by azacyclopentane-2-one and N-methylolacetamide (1: 2) and explored the synergetic effect of hydrogen-bonding interactions among them and their thermodynamic properties. The findings indicate that the synergetic effects can enhance the ability of azone to change the original conformation of ceramides and even break the original hydrogen bonds, which is more beneficial for azone to destroy the 3D network structure of ceramides. When azone interacts with ceramide, the order of action tends to interact with one molecule of ceramide first and then with another molecule of ceramide.
The synergetic effects of hydrogen-bonding interactions in ternary systems were computed at the B3LYP/6-311 + + G** and MP2(full)/6-311 + + G** levels. Thermodynamic parameters for two ternary-complex routes were worked out at the B3LYP/aug-cc-pVDZ level. The shift of the electron density occurring simultaneously with trimer formation was analyzed at the MP2(full)/6-311 + + G** level. The above calculations were carried out using the Gaussian 03 program packages. Atoms in molecules (AIM) method and the AIMPAC program showed the topological charge density at the MP2(full)/6-311 + + G** level. The synergetic effects of hydrogen-bonding interactions and thermodynamic property in the 1: 2 (azacyclopentane-2-one: N-methylolacetamide) ternary systems were investigated using the B3LYP and MP2(full) methods.
使用化学渗透增强剂来提高渗透效果是经皮给药系统中的一种重要策略。氮酮是一种广泛应用的经皮吸收促进剂，用于经皮药物传递。为了阐明氮酮的促渗机制，我们选择了由氮杂环戊烷-2-酮和 N-羟甲基乙酰胺（1:2）形成的三元体系，并探索了它们之间氢键相互作用的协同效应及其热力学性质。结果表明，协同效应可以增强氮酮改变神经酰胺原始构象的能力，甚至破坏原始氢键，这更有利于氮酮破坏神经酰胺的 3D 网络结构。当氮酮与神经酰胺相互作用时，作用顺序趋于先与一个神经酰胺分子相互作用，然后再与另一个神经酰胺分子相互作用。
在 B3LYP/6-311 + + G和 MP2(full)/6-311 + + G水平上计算了三元体系中氢键相互作用的协同效应。在 B3LYP/aug-cc-pVDZ 水平上计算了两条三元络合物途径的热力学参数。在 MP2(full)/6-311 + + G水平上分析了三聚体形成时同时发生的电子密度位移。上述计算使用 Gaussian 03 程序包进行。分子中的原子（AIM）方法和 AIMPAC 程序在 MP2(full)/6-311 + + G水平上显示了拓扑电荷密度。使用 B3LYP 和 MP2(full)方法研究了 1:2（氮杂环戊烷-2-酮：N-羟甲基乙酰胺）三元体系中氢键相互作用的协同效应和热力学性质。
