蚊虫驱避化合物与人体分泌的引诱物L-乳酸分子间弱相互作用的计算

Calculation of the weak interaction between mosquito repellents and the human-secreted attractant L-lactic acid

【目的】驱避剂是蚊虫防治的重要手段之一。前期研究发现,在驱避剂的使用过程中,驱避化合物分子与人体分泌的引诱物分子存在相互作用。为深入了解这种相互作用的本质,本研究从量子化学的角度分析了3种驱避化合物分子与引诱物分子L-乳酸相互作用过程中几何结构、结合能、电荷布居和热力学参数等量化参数的变化,以期从计算机模拟角度揭示驱避化合物分子与引诱物分子相互作用的形式、强度和规律。【方法】本研究选择了3种在驱蚊方面具有代表性的驱避化合物,即8-羟基别二氢葛缕醇甲酸酯(R1)、羟基香茅醛-1,2-丙二醇缩醛(R2)和N,N-二乙基间甲基苯甲酰胺(避蚊胺)(DEET),使用Gaussian 09量子化学计算程序包对驱避化合物分子单体R1,R2,DEET和人体引诱物分子单体L-乳酸以及驱避化合物分子与L-乳酸的缔合体进行结构构建;在M06-2X-D3/6-311G(d,p)水平上优化所有单体、缔合体的几何结构,并做振动频率计算;在M06-2X-D3/6-311+G(d,p)水平上对单体、缔合体进行单点能计算。【结果】驱避化合物分子R1,R2和DEET与L-乳酸的缔合距离在2.64~2.74之间,缔合角度在170~175°之间,缔合后,L-乳酸羧基上氧氢键分别伸长0.019,0.029和0.022;R1,R2和DEET与L-乳酸缔合过程的结合能ΔE依次为-50.278,-72.385和-66.977 k J/mol,焓变ΔH分别为-43.715,-65.559和-60.465 k J/mol,熵变ΔS分别为-0.138,-0.159和-0.157 k J/mol·K,自由能变ΔG分别为-2.652,-18.090和-13.784 k J/mol;R1,R2和DEET与L-乳酸缔合过程中,L-乳酸的总净电荷由0 e分别变为-0.0248,-0.0250和-0.0168 e。【结论】计算结果表明,驱避化合物分子R1,R2和DEET与L-乳酸均通过中强氢键缔合,并且R2与L-乳酸的氢键作用最强,形成的缔合体也最为稳定。

【Aim】Using repellent is one of the most important methods for mosquito control. In our previous study,we found that there is an interaction between repellent molecules and human-secreted attractant molecules during the use of repellents. To understand the true nature of this interaction,in this study the interactions between three repellents and one attractant L-lactic acid were explored throughcomputational quantum chemistry based on the analysis of numerical changes of geometric structure,binding energy,charge population and thermodynamic parameters. This study might reveal the form,strength and law of the interactions between the repellent molecules and the human-secreted attractant molecules in silico. 【Methods 】 The structures of three representative mosquito repellents 8-hydroxylcarveol formate（ R1）,hydroxy citronellal-1,2-propanediol acetal（ R2） and N,N-diethyl-3-methyl benzoyl amide（ DEET）,the attractant L-lactic acid,and their complexes were constructed by using Gaussian 09 software package. Geometry optimizations and vibration frequency calculations of the repellents,the attractant and their complexes were done at the M06-2X-D3/6-311G（ d,p） level. The single point energy of the repellents,the attractant and their complexes were calculated at the M06-2XD3/6-311 ＋ G（ d,p） level. 【Results】The association distances and angles between the repellents R1,R2 and DEET and the attractant L-lactic acid were among 2. 64-2. 74  and 170-175°,respectively,and after the association,the bond length of oxygen hydrogen bond in carboxyl of L-lactic acid were stretched to 0. 019,0. 029 and 0. 022 ,respectively. The binding energies（ ΔE） of the association process were-50. 278,-72. 385 and-66. 977 k J/mol,the enthalpy change（ ΔH）-43. 715,-65. 559 and-60. 465 k J/mol,the entropy change（ ΔS）-0. 138,-0. 159 and-0. 157 k J/mol·K,the free energy（ ΔG）-2. 652,-18. 090 and-13. 784 k J/mol,and the total net charge of L-lactic acid varied from 0 e to-0. 0248,-0. 0250 and-0. 0168 e,respectively. 【Conclusion】The repellents R1,R2 and DEET and the attractant L-lactic acid are associated by moderately strong hydrogen bond.The hydrogen bond between R2 and L-lactic acid are the strongest,and the complex formed is the most stable.