Phenolic acids are naturally occurring compounds that are known for their antioxidant and antiradical activity. We present experimental and theoretical studies on the antioxidant potential of the set of 22 phenolic acids with different models of hydroxylation and methoxylation of aromatic rings. Ferric reducing antioxidant power assay was used to evaluate this property. 2,3-dihydroxybenzoic acid was found to be the strongest antioxidant, while mono hydroxylated and methoxylated structures had the lowest activities. A comprehensive structure–activity investigation with density functional theory methods elucidated the influence of compounds topology, resonance stabilization, and intramolecular hydrogen bonding on the exhibited activity. The key factor was found to be a presence of two or more hydroxyl groups being located in ortho or para position to each other. Finally, the quantitative structure–activity relationship approach was used to build a multiple linear regression model describing the dependence of antioxidant activity on structure of compounds, using features exclusively related to their topology. Coefficients of determination for training set and for the test set equaled 0.9918 and 0.9993 respectively, and Q2 value for leave-one-out was 0.9716. In addition, the presented model was used to predict activities of phenolic acids that haven’t been tested here experimentally.

Flavonoids are known for their antiradical capacity, and this ability is strongly structure-dependent. In this research, the activity of flavones and flavonols in a water solvent was studied with the density functional theory methods. These included examination of flavonoids’ molecular and radical structures with natural bonding orbitals analysis, spin density analysis and frontier molecular orbitals theory. Calculations of determinants were performed: specific, for the three possible mechanisms of action—hydrogen atom transfer (HAT), electron transfer–proton transfer (ETPT) and sequential proton loss electron transfer (SPLET); and the unspecific—reorganization enthalpy (RE) and hydrogen abstraction enthalpy (HAE). Intramolecular hydrogen bonding, catechol moiety activity and the probability of electron density swap between rings were all established. Hydrogen bonding seems to be much more important than the conjugation effect, because some structures tends to form more intramolecular hydrogen bonds instead of being completely planar. The very first hydrogen abstraction mechanism in a water solvent is SPLET, and the most privileged abstraction site, indicated by HAE, can be associated with the C3 hydroxyl group of flavonols and C4’ hydroxyl group of flavones. For the catechol moiety, an intramolecular reorganization to an o-benzoquinone-like structure occurs, and the ETPT is favored as the second abstraction mechanism.

Resonance Raman optical activity (RROA) possesses all aspects of a sensitive tool for molecular detection, but its measurement remains challenging. We demonstrate that reliable recording of RROA of chiral colorful compounds is possible, but only after considering the effect of the electronic circular dichroism (ECD) on the ROA spectra induced by the dissolved chiral compound. We show RROA for a number of model vitamin B12 derivatives that are chemically similar but exhibit distinctively different spectroscopic behavior. The ECD/ROA effect is proportional to the concentration and dependent on the optical pathlength of the light propagating through the sample. It can severely alter relative band intensities and signs in the natural RROA spectra. The spectra analyses are supported by computational modeling based on density functional theory. Neglecting the ECD effect during ROA measurement can lead to misinterpretation of the recorded spectra and erroneous conclusions about the molecular structure.

The antioxidative nature of chemicals is now routinely studied using computational quantum chemistry. Scientists are constantly proposing new approaches to investigate those methods, and the subject is evolving at a rapid pace. The goal of this review is to collect, consolidate, and present current trends in a clear, methodical, and reference-rich manner. This paper is divided into several sections, each of which corresponds to a different stage of elaborations: preliminary concerns, electronic structure analysis, and general reactivity (thermochemistry and kinetics). The sections are further subdivided based on methodologies used. Concluding remarks and future perspectives are presented based on the remaining elements.