Symmetry in Acid-Base Chemistry

Most organic molecules, including natural products, drugs, and toxicants, contain functional groups that display acid-base properties. These properties, have mainly been described by the Brønsted and Lowry theory for proton-transfer reactions and/or by the Lewis theory for acid-base adduct formations. Physicochemical parameters of these processes can be determined using various experimental techniques for both solution and/or gas phases. They can also be estimated by quantum-chemical methods.

A collection of a large number of physicochemical data obtained in different laboratories revealed similarities and discrepancies between acidity-basicity scales in vacuo and solution and in structural (internal) and medium (external) effects. Some analogies in electron and charge delocalization, intra- and intermolecular interactions (e.g., hydrogen bonding), various types of isomerism, as well as prototropic tautomerism have also been reported. Although the history of acid-base chemistry has more than 100 years, investigations on the structures of acids and bases and their reactions are still very exciting. For example, in the Web of Science, one can find more than 1000 articles published on proton-transfer reactions in 2022.

This Special Issue entitled “Symmetry in Acid-Base Chemistry” belongs to the section of “Chemistry and Symmetry/Asymmetry”. It comprises five original articles by 30 authors [1,2,3,4,5] (from Ukraine, Germany, Estonia, France, Portugal, Hungary, Turkey, Czech Republic, Slovakia, Denmark, Iran, and Poland) who discuss the most important questions of modern acid-base chemistry. Authors documented and analyzed only new original results both experimental [2] and theoretical [1,3,4,5] that have been reported for the first time.

Taking into account some differences in existing pK_a scales and discrepancies in acidity and/or basicity parameters measured in aqueous solution and other solvents, Leito (Estonia) and his co-workers (Germany, Estonia, France, Portugal, Hungary, Turkey, Czech Republic, Slovakia, and Denmark) [2] in their entirely experimental work described some symmetric cells for measurement of unified pH values. These electrochemical cells have been tested by chemists in different countries. Authors proved by potentiometric experiments that the tested cells are suitable for the unified pH measurements. These experiments for the unified pH scale can open in future possibilities of comparisons of acidity and basicity parameters determined in different solvents.

Authors of the theoretical works reported various isomeric phenomena (conformational and configurational isomerism, and/or prototropic tautomerism) possible for acids and bases, and showed interesting relations between various types of isomerism and intramolecular interactions. They also discussed the consequences of these phenomena on the acid-base properties of investigated compounds. For investigations, they selected some simple monofunctional compounds as well as more complex polyfunctional π-electron systems. They employed different quantum-chemical methods, such as the density functional theory (DFT), second-order Moller-Plesset perturbation theory (MP2), Gaussian-2 theory (G2), and/or MP2 variant of Gaussian-2 theory {G2(MP2)} for isolated molecules, and also the polarizable continuum model (PCM) for hydrated species.

For example, Brovarets’ and Hovorun (Ukraine) [1] chose very complex quercetin, an important flavonoid containing three six-membered rings and five exocyclic OH groups, well-recognized for its anti-oxidant, anti-inflammation, and others therapeutic properties. The article published in this Special Issue is a fourth part of their structural studies on conformation, rings rotation, and tautomerism of quercetin. Performing detailed conformational analysis, the authors identified numerous transition states for rotational isomerism about the exocyclic C−O single bonds and estimated the Gibbs free energy barriers of activation under the standard conditions. Between the exocyclic groups, they additionally detected some important intramolecular specific interactions that partially control conformational dynamics of the OH groups.

In the next theoretical article published in the Special Issue, Dobrowolski and Ostrowski (Poland) [3] defined and discussed a new exciting inversion in a cage isomerism as an isomerism in the three-component system of molecules HX (X: F or Cl), NH₃, and a cage C60 (amphoteric fullerene). In this three-molecular system, one of the simple molecules (HX or NH₃) has been located inside of the C60 cage and the other one outside of the cage. Using DFT calculations, the authors found that the C60 molecule with HX inside or outside of the cage becomes an acid for the NH₃ base positioned outside or inside of the cage.

Keto-enol equilibria have been documented for five azulenols in my theoretical article [4]. In this work, the stabilities of potential enol rotamers and possible keto tautomers have been analyzed in the gas phase and also in aqueous solution using the DFT and PCM methods. These studies showed interesting geometric and energetic differences between tautomers of azulenols and naphthols (constitutional isomers of azulenols). For naphthols, the keto forms can be neglected, whereas at least one keto isomer significantly contributes to the tautomeric mixture of each azulenol. Interestingly, few aromatic azulenols seem to be stronger acids than naphthols.

The last article accepted for the Special Issue presents a complete theoretical analysis of isomeric forms of neutral and protonated polyfunctional push-pull nitriles with various electron donor groups [5]. It has been submitted by Gal (France) and his co-workers (Poland, France, and Iran). Authors showed by DFT, G2, and G2MP2 calculations that the cyano N-atom is the favored site of protonation in all investigated molecules. They employed the complete isomeric investigations to the study of both the microscopic basicity parameters for each potential protonation N-site in individual isomers as well as the macroscopic basicity parameters for the isomeric mixtures. Electron-donor effects of pushing groups {X: NH₂, NMe₂, N=C(NH₂)₂, N=C(NMe₂)₂, and N=P(NMe₂)₃}, separated from the C≡N group by the methylenecyclopropene and cyclopropenimine π-electron systems, have been found to be parallel to those observed in the directly substituted nitrile series X–C≡N. Although an attenuation factor of substituent effects is close to 0.6, many push-pull nitrile derivatives are stronger bases in the gas phase than proton sponge, one of the most basic compounds in the family of amines.