Structural Chemistry

, Volume 30, Issue 1, pp 23–35 | Cite as

Theoretical and experimental analysis of the antioxidant features of substituted phenol and aniline model compounds

  • William Horton
  • Swarada Peerannawar
  • Béla TörökEmail author
  • Marianna TörökEmail author


Although natural polyphenols have attracted extended attention as antioxidants, there is only limited information available on their structure-activity relationship (SAR). In addition, while often having significant antioxidant activity, amino group-containing compounds have only been sporadically studied. Often, the complex structure makes studying the individual contribution of aromatic OH or NH2 groups on the activity of these antioxidants difficult. In this work, several substituted simple phenols and anilines were selected as model compounds. Both the experimental radical scavenging activity and major structural descriptors have been determined to gain more insights into the potential SAR. Physicochemical properties pertaining to energetic and structural parameters were determined and experimental data gathered from three antioxidant assays to identify fundamental features with reasonable effect on antioxidant activity. Density functional theory (DFT) calculations were carried out at the B3LYP/6-31G(d,p) level to determine the N–H and O–H bond distances, dipole moments, logP values, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbital energies, HOMO-LUMO gaps, radical spin densities, proton affinities, and ionization potentials. The compounds were screened for activity against the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1picrylhydrazyl (DPPH), and peroxyl (ORAC assay) radicals. Based on the results, ABTS antioxidant activity was selected for further investigations to observe correlations with the calculated properties. The HOMO energies, bond-dissociation energy values, HOMO-LUMO gap energies, dipole moment, proton affinity, and the Hammett constants appear to show meaningful correlation with the experimental data.


Phenols Anilines Antioxidant capacity Radical scavenging DFT calculations Structure-activity relationship 



highest occupied molecular orbital


lowest unoccupied molecular orbital


2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)




oxygen radical absorbance capacity


multiple sclerosis


hydrogen atom transfer


single-electron transfer


sequential proton loss electron transfer


dimethyl sulfoxide

μ (D)

dipole moment


bond-dissociation energy


ionization potential


proton affinity


Hammett constant


Funding information

This study received financial support from the University of Massachusetts Boston.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of Massachusetts BostonBostonUSA

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