A Computational Study of the Chemical Reactivity of the (2S,3R) and (2S,3S) Isomers of Dehydrated Hydroxycitric Acid

A computational investigation about the chemical reactivity of hibiscus acid (HA) and garcinia acid (GA) diastereoisomers was conducted using the X/6-311G(d,p) theoretical level (where X = B3LYP, B3PW91, BHandHLYP and WB97XD). Analysis of global reactivity descriptors revealed similar behavior for both diastereoisomers. However, Fukui function calculations highlighted differences in local active site distribution attributed to the orientation of the hydroxyl group at C3 in the oxolane structure. Variations in carboxyl group orientations were observed to induce distinct local reactivities on the HA and GA due to the presence of different intramolecular interactions, which are impacting their chemical properties. Also, specific sites susceptible to nucleophilic, electrophilic, and free radical attacks were identified. NBO results were used to estimate the donor-acceptor interactions in HA and GA. The results suggest that the most favorable interactions are LP(2)O17 and BD*(2) C9-O19. Additionally, an analysis of the bond critical points (BCPs) indicates that the Laplacian of the density in GA is higher compared to HA, suggesting that the BCP in GA is more sensitive to variations in the surrounding electronic density. These findings could provide an explanation for the observed differences in reactivity between these compounds.