Experimental and computational investigations of citral-2-hydroxypropyl-β-cyclodextrin inclusion complex and its innovative application as an acaricidal agent

The formation of inclusion complexes with cyclodextrins offers an efficient solution to the limited application of citral (CIT) in the food and pharmaceutical industries and in agrochemical development due to its high volatility and low water dispersibility. The objective of this research was to elucidate the structure and understand the formation mechanism of the inclusion complex between CIT and 2-hydroxypropyl-β-cyclodextrin (denominated ICHβCIT) by kneading method through a combination of experimental techniques and computational studies. Furthermore, to evaluate its acaricidal activity in vitro in Rhipicephalus microplus larvae. The investigation using experimental techniques (FTIR, PXRD, SEM, NMR, and TGA) and computational studies (NMR theoretical, NCI, and 1500 ns MD simulation) revealed the formation of a stable IC with low binding affinity. Furthermore, the main driving force in ICHβCIT was identified as van der Waals interactions. Biological tests against R. microplus provided evidence that IC formation was able to prolong the biological activity of CIT (86.30 to 81.59 %) when compared to free CIT (90 to 64.61 %) and the physical mixture (79.42 to 60.86 %) for 48 h. Therefore, ICHβCIT adds an innovative application as an acaricidal agent contributing for development of products for animal health and welfare.