A computational study of the structure‐activity relationships of some p‐hydroxybenzoic acid antioxidants

Abstract

Equilibrium structures of all derivatized systems of p‐hydroxybenzoic acid, 3,4‐dihydroxybenzoic acid, 3‐methoxy‐4‐hydroxybenzoic acid, and 3,5‐dimethoxy‐4‐hydroxybenzoic acid and calculated structural and energetic molecular descriptors were determined at the B3LYP/6‐31+G(d) density functional theoretical level in an attempt to study their structure‐activity relationships (SAR). The theoretical antioxidant activity trend, derived in terms of hydrogen‐donating capacity against radicals in lipid systems, is in excellent agreement with the experimental one. The lower antioxidant activity of benzoates, experimentally found relative to the homologous cinnamates, could be due to (i) their lower spin delocalization, (ii) their higher calculated heats of formation values in forming radicals (ΔHOF), and (iii) the much stronger electron‐withdrawing effect of the‐COOH group than‐CH=CHCOOH. The low calculated dipole moment values of the global minimum structures of the antioxidants could facilitate their solubilities in nonpolar solvents, hence the ease of hydrogen abstraction. However, highest occupied molecular orbital (HOMO) eigenvalues can neither predict antioxidant activity nor differentiate the same activity between two series of structurally related compounds. Again, density functional theory calculations provide a good molecular descriptor, ΔHOF, to correlate with the antioxidant activity in molecules showing similar structural characteristics.

Recent Developments in Effective Antioxidants: The Structure and Antioxidant Properties

“…Low antioxidant activity of benzoate radicals in comparison to radical homologs of cinnamic acid results from a smaller spin relocation of the COOH group compared to the -CH = CHCOOH group. The spin density of the carboxyl group is insignificant, and most of the spins are located in the ring or within the oxygen atoms of the substituent groups [ 102 , 105 ].…”

Reactivity of phenolic compounds towards free radicals under in vitro conditions

“…Propyl gallate and gallic acid are very strong reducing agents, owing to the presence of three hydroxyl groups. The antioxidant efficiency of monophenols is increased substantially by one or two methoxy substitutions at the o-position relative to the hydroxyl (Vafiadis and Bakalbassis 2003;Cuvelier et al 1992) which explains the reducing power in the order Sina > Feru > Coum.…”

Antiradical potential of phenolic compounds fingerprints of propolis extracts: DFT approach

“…However, a knowledge of the geometries of the phenolic compound is necessary for investigate the structure-activity relationship [14,29,30]. The optimized molecular structure showing the atomic labeling and numbering are showed in Fig.…”