Computational study of the reactivity and physiochemical properties of Enugenol, 2-Methoxy-4-Oxyranyl Methylphenol and 2-methoxy-4-allylidene-2,5-Cyclohexadiene-1-one
Creators: name: Jhonatan Rabanal Sanchez
Publisher: name: F1000 Research Limited
Year: 2019

description: Introduction: Eugenol is a phenylpropanoid, obtained from various medicinal plants, with pharmacological potential. A previous study showed that eugenol can be biotransformed by cytochrome P450 (CYP); This study found that carbon atoms 1 and 2 are prone to epoxidation, carbon 3 to hydroxylation and carbon 7 to o-dealkylation, likewise, this study found that eugenol complies with Lipinski's rule of 5. Materials and methods: The pharmacological potential of eugenol and derivatives, 2-methoxy-4-oxyranyl methylphenol (2M4O) and 2-methoxy-4-allylidene-2,5-cyclohexadiene-1-one (2M4A), was evaluated using the methodology QSAR (quantitative structure-activity relationship), for which the following physicochemical properties were determined: topological polar surface area (TPSA), molar refractivity, pKa, isoelectric point, partition coefficient (Log P) , number of hydrogen donors and acceptors, fraction of saturated carbons in sp3 (FSP3), volume of van der Waals and surface area of ​​van der Waals. The ChemAxon software was used to determine these properties. In addition, the Gibbs free energy variation of formation under standard reaction conditions (ΔfG °) was determined, the Joback method was used and the calculations were made using the Cheméo virtual platform. The chemical shift of the 1H NMR was also determined, using the software predictor 1D 1H NMR spectra. In addition, the reactivity of eugenol and derivatives against CYP2C was analyzed, the activation energy and the solvent accessible surface area (SASA) of the carbon atoms were determined. The EAWAG-BBD software was used to determine the reactivity of these molecules in aerobic microorganisms. Finally, the Spearman correlation coefficient of the following variables was determined: arithmetic mean of the chemical shift of the 1H NMR (independent variable) and the activation energy of carbon atoms (dependent variable), besides this coefficient was determined to the following variables: arithmetic mean of the chemical shift of 1H NMR (independent variable) and SASA of carbon atoms (dependent variable). Results and discussion: It was found that the eugenol and derivatives comply with the rules of 5 of Lipinski, so they would have a pharmacological potential. Also eugenol and 2M4O have a negative ΔfG °, so they would be more reactive than 2M4A. In the analysis of the chemical shift of the 1H NMR, higher values ​​were found in hydrogen atoms linked to carbon-carbon double bonds, this due to the pi (π) bonds. Regarding the reactivity against CYP2C, this study found that carbons 1,2,3 and 7 of eugenol and 2M4O have lower activation energy, in the same way carbons 1 and 7 of 2M4A have lower activation energy. This indicates that these carbons could be the target of chemical reactions catalyzed by CYP2C. In addition, carbons 1 and 7 of eugenol and derivatives have a higher SASA, which would allow them to participate in chemical reactions. It was found that reactions in aerobic microorganisms occur mainly in carbons 1,2,3 and 7. Finally, there is a positive linear correlation between the chemical shift of 1 H NMR and the activation energy of carbon atoms, plus a correlation negative linear between the chemical shift of the 1H NMR and the SASA of carbon atoms. Conclusions: Eugenol and its derivatives have properties that position them as candidates for drugs, in addition they can be metabolized by CYP and by aerobic microorganisms.