Computational Chemistry Study: Analyzing the Most Stable Conformations of Linalool

Overview

Linalool is a fragrant monoterpene alcohol present in essential oils like lavender and basil. It exhibits significant biological properties, including antibacterial and sterilization characteristics, and is widely used in the pharmaceutical and food industries. Its flexible structure allows for multiple conformations, which give linalool unique chemical and biological properties. A study by Wu et al. demonstrated the bactericidal properties of linalool-rich essential oils using Density Functional Theory (DFT) calculations. However, the study did not identify the most stable conformation of linalool before conducting the analysis. This work focused on addressing this by conducting conformational searches using computational tools such as xTB, CREST, and CENSO. Conformation #1 was identified as the most stable, with the lowest energy (-466.315436 Eh) and a Boltzmann weight of 93.55%. Natural Bond Orbital (NBO) analysis revealed a significant OHâ€“Ï€ interaction in Conformation #1. The hydroxyl group interacts with the Ï€-electrons of the faraway double bond, forming a stabilizing cyclic structure. Specifically, the donor orbital (BD(34) C=C) transfers electron density to the acceptor antibond orbital (BD*(53) OH), stabilizing the molecule with an interaction energy of 5.51 kcal/mol. These interactions transfer electron density from the double bond and strengthen the hydrogen bonding. The cyclic stabilization may explain the biochemical reactivity of linalool, especially its antibacterial properties. Understanding this conformation helps improve the knowledge of linaloolâ€™s behavior, potentially aiding its application in various industries. This analysis fills a gap to determine how molecular structure is related to the functional properties of linalool.