A Statistically Supported Antioxidant Activity DFT Benchmark—The Effects of Hartree–Fock Exchange and Basis Set Selection on Accuracy and Resources Uptake

Abstract

Polyphenolic compounds are now widely studied using computational chemistry approaches, the most popular of which is Density Functional Theory. To ease this process, it is critical to identify the optimal level of theory in terms of both accuracy and resource usage—a challenge we tackle in this study. Eleven DFT functionals with varied Hartree–Fock exchange values, both global and range-separated hybrids, were combined with 14 differently augmented basis sets to calculate the reactivity indices of caffeic acid, a phenolic acid representative, and compare them to experimental data or a high-level of theory outcome. Aside from the main course, a validation of the widely used Janak’s theorem in the establishment of vertical ionization potential and vertical electron affinity was evaluated. To investigate what influences the values of the properties under consideration, linear regression models were developed and thoroughly discussed. The results were utilized to compute the scores, which let us determine the best and worst combinations and make broad suggestions on the final option. The study demonstrates that M06–2X/6–311G(d,p) is the best fit for such research, and, curiously, it is not necessarily essential to include a diffuse function to produce satisfactory results.

Current Trends in Computational Quantum Chemistry Studies on Antioxidant Radical Scavenging Activity

“…Given their newness, it is visible that these two Minnesota functionals are gradually displacing B3LYP since their release. This could be a result of their superior performance in estimating thermochemistry, kinetic and noncovalent interactions of nonmetal elements, as well as energies of reactions involving free radicals, which they predict extremely close to actual data, as claimed by the developers − and continue to be substantiated by independent scientists, either in the course of original research − ,,,,, or in benchmarks. − On the other hand, several researchers who used both B3LYP and one of Truhlar’s global hybrids noted that while B3LYP tends to underestimate energies there are no substantial differences and the reactivity patterns hold when the same basis set is used. ,,,, …”

“…This bad habit have its consequences in the performance of computations. Increasing the number of basis functions is known to increase task processing time, and it has recently been established that those from the Dunning’s and Ahlrich’s families are particulary vulnerable . Furthermore, whereas functionals should be kept constant throughout the research, the basis set does not, namely while one can be used for electronic structure investigations, other may be applied for thermochemistry, which allows maneuvering them in order to obtain the best results at the lowest possible cost.…”

“…These approximations of orbitals egeinvalues as ionization potential or electron affinity, however, ignore electron correlation and are highly dependent on the method and basis set employed ,,, . This poses further problems for they serve as the foundation for a slew of global descriptive parameters related to the electrophilic character of the species (Table ) meaning their improper values may lead to further errors in the study and invalid conclusions.…”

“…79 Moreover, although the presence of polarization functions is undeniably important for determining the energy of highly polarized bonds, the role diffusion functions, which are widely regarded as necessary for accurately modeling electron clouds in ionic systems and radical involving pathways, must be addressed more thoroughly. Still, the recent research 153 has shed new light on that issue for it was discovered that using 6-311G(d,p) for overall antioxidant studies produces the best results in terms of both the accuracy between theroetical outcomes and experimental values, as well as computational resource uptake. Further confirmation on that indulging issue and more detailed studies on the role of the basis set are welcome.…”

“…On the other hand, M062X/6-311G(d,p) level of theory has been found to approximate energies of frontier molecular orbitals with an error no greater than 0.5eV from the ones calculated in the direct vertical manner. 153 The ability to accept electrons. It is inversely proportional to chemical hardness.…”