The relationships between electronic structure particularities and antioxidant activity of some chemical compounds are considered on the basis of the density functional theory (DFT) calculations of reactions between some natural phenolic antioxidants (gallic, caffeic, p-coumaric, and other acids), as well as dihydroxyfumaric acid, and the stable radicals ABTS•+ and DPPH• in water, ethanol, and methanol. Particular attention is paid to the processes of the primary proton transfer between neutral molecules of the above antioxidants and molecules of these solvents. The important factors are also considered: the formation of the charge transfer complexes (CTC) between the anionic forms of these antioxidants and the radicals, and possible tautomeric effects essentially changing the pre-reactional structures of the investigated antioxidant molecules and their anions. The quantitative relationships between the electronic structure parameters and the antioxidant activity of some short chain n-alkanes with radicals OH• and NO3• are also discussed.
TopIntroduction
Practically in most cases, the experimental investigation of the antioxidant activity of chemical compounds establishes only its relative values in the series of the studied chemical substances supposed to be antioxidants. However, the data obtained in this way do not allow us to make an adequate forecast in the search for new antioxidants. At the same time, it is well known that many properties of any molecular system are determined by the particularities of its electronic structure. Therefore, in order to reveal a possible mechanism of redox reactions for oxidant-antioxidant systems, it is advisable to develop a theoretical model that could describe some correlation between the value of antioxidant ability and the calculated electronic structure parameters, such as, for example, the charges on the atoms (qi), the energies of the frontier (and the nearest) molecular orbitals (Ei), interatomic distances in its structure, etc. In addition, for this purpose many DFT-based quantum reactivity descriptors as, for instance, chemical hardness (η), softness (σ), electronegativity (χ), Fukui indexes, etc., are also being used. Most often all these reactivity descriptors are calculated by the DFT B3LYP method (Stephens, 1994)which allows one the adequate description of the electronic ground state properties of various organic chemical antioxidants and other biologically active molecules (see the reviews (Spiegel, 2022), (Villaverde, 2020). The following usage of the multiple regression analysis applied to establish the Structure-Activity Relationship (SAR) or Quantitative Structure-Activity Relationship (QSAR) between the antioxidant activity and the above reactivity descriptors leads only to the revealing of some new correlation dependency. However, this way doesn’t approach us to the understanding of the sought antioxidant reaction mechanism.
In this connection, we will consider a number of recently published papers that are devoted to establishing the dependence QSAR based on the above-mentioned descriptors. In Ref. (Muliadi, 2021) devoted to the study of myristicin derivatives the following correlation Equation (1) was found that describes the logarithm of their distribution coefficient P in the octanol-water binary system, i.e., the possibility of penetration of an antioxidant into the lipid cell layer:log10 P = -2.600 + 0.006 IW- 1.558 q(C8) - 6.532 EHOMO + 0.014 PSA + 0.133 MD,(1) where n = 6, and R2 = 0.926.
In Eq.(1) for each of the studied in (Muliadi, 2021)myristicin derivatives, q(C8) and EHOMO are respectively the charges on its carbon atom C8 and the energy of its HOMO obtained by means of the DFT B3LYP calculations. IW, PSA, and MD are respectively its Wiener Index, its polar surface area, and its dipole moment. One can see, that all these one-particle variables of Eq.(1) were determined by means of multiple regression analysis.
In the work (Djeradi, 2014), which is devoted to DFT-based reaction ability combined with QSAR of flavonoid derivatives as antioxidants, it was shown that the so-called condensed-to-atom Fukui functions (Pratim, 2009) play an important role in the found in (Djeradi, 2014) QSAR dependence. Further, in the work (Sarkar, 2012) (which is also devoted to the study of flavonoid compounds) it was found the QSAR equation describing adequately the radical scavenging antioxidant activity of a wide series of flavonoids using DFT based quantum chemical descriptors – the so-called “group frontier electron density” along with parameters of molecular hardness and the parameter of “group philicity” for a nucleophilic attack (Sarkar, 2012). It is to note here that both the above group parameters are related to different cycles of the studied flavonoid molecular systems.