Abstract: 【Aim】 Mosquito repellents are a group of compounds which can protect human from mosquito biting. However, the repelling mechanisms are still unclear. In this study, theoretical calculations were applied to investigate the molecular association between four important human-derived attractants (acetic acid, propionic acid, butyric acid and pentanoic acid) and twenty-two terpenoid repellents, to find out the relationship between this kind of interaction and repellency, and so to clarify the repelling mechanisms from a new perspective.【Methods】 Structures of attractants, repellents and attractant-repellent complexes were built and optimized by GAUSS View and GAUSSIAN, and association energy and geometrical parameters were obtained. Descriptors for model building were calculated by AMPAC and CODESSA. The quantitative structure-activity relationship (QSAR) models were built to analyze the relationship between the structural descriptors and the logarithm value of the corrected repelling time (logCRR) against Aedes albopictus. 【Results】 The association energy between four carboxylic acids and twenty-two terpenoid repellents is between 18 and 20 kJ/mol, and the association distance and angle are fluctuating from 2.0 to 2.5 Å and from 110° to 180°, respectively, which exactly fit the characteristics of hydrogen bonding interaction. Four obtained QSAR models were statistically satisfying, and the R² values of any one of these four parametric models were above 0.9. Every model contained the descriptors generated from attractant-repellent complex, showing a significant correlation between attractant-repellent association and the logCRR. 【Conclusion】 Hydrogen bonding associations with moderate strength exist between four carboxylic acids and terpenoid repellents, and such kinds of associations deeply affect the repellency. This study provides a preliminary support to the existence of attractant-repellent association and sets up a foundation for the research of repelling mechanism from a new perspective.

Key words: Terpenoid, mosquito repellent, carboxylic acid, molecular association, repellency, quantitative structure-activity relationship (QSAR)