A theoretical antioxidant pharmacophore for natural hydroxycinnamic acids

Abstract

Abstract:The structure-activity relationship analysis has been performed for trans-and cis-hydroxycinnamic acids, to determine their theoretical antioxidant pharmacophore. Based on the detailed conformational studies, the most stable rotamers have been selected. We have analyzed the descriptors of four antioxidant mechanisms important in free radical scavenging: hydrogen atom transfer, sequential proton loss electron transfer, single electron transfer -proton transfer and transition metal chelation, based on the B3LYP/6-311++G(2d,2p) calculations in vacuum and polar media. The results explain the activity difference between cinnamic acid and its derivatives. The descending order of antioxidant potential is as follows:The results have shown that transisomers indicate higher reactivity than cis-and may be considered as good antioxidants. It has been determined that the highest antioxidant ability is related to the hydroxyl group in para position, supported by planar structure and stability of radical forms. π-Type delocalization of unpaired electron on aromatic ring, double bond and para O-atom is the key to radical stabilization. The ortho-dihydroxy substitution in benzene ring positively influences the ability to neutralize free radicals and makes caffeic acid the antioxidant pharmacophore of hydroxycinnamic acids.

Quantum Chemical Investigation on the Antioxidant Activity of Neutral and Anionic Forms of Juglone: Metal Chelation and Its Effect on Radical Scavenging Activity

“…This shows that the sequential proton loss electron transfer is the preferred mechanism in water. This result is in good agreement with those found in the literature with the polar solvents [41][42][43][44][45][46][47][48]. In water, the Cu(II) chelate is found to be the most stable and the most reactive.…”

Anthocyanin Encapsulated by Ferulic Acid-Grafted-Maltodextrin (FA-g-MD) Microcapsules Potentially Improved its Free Radical Scavenging Capabilities Against H2O2-Induced Oxidative Stress

“…As shown in Figure 3A, ANC, FA-g-MD and their combination exhibited a concentration-dependent (0.0625–1 mg/mL) radical-scavenging capacity. Obviously, ANC and FA-g-MD presented good antioxidant activities, as already demonstrated by previous reports [26]. These compounds are postulated to have very good electron-donating abilities due to p -OH and other electron-donating functional groups.…”

Rationale on the High Radical Scavenging Capacity of Betalains

“…The gas phase enthalpies of the proton (6.197 kJ mol −1 ), electron (3.146 kJ mol −1 ) and hydrogen atom (–1306 kJ mol −1 ), as well as the solvation enthalpies (water) of the proton (–1055.7 kJ mol −1 ), electron (–77.5 kJ mol −1 ), and hydrogen atom (–4 kJ mol −1 ) were taken from the literature [35,36]. Phenol and the phenoxyl radical were used as reference compounds to calculate the ΔBDE PhOH (Equation (6)) [37].…”