On Prototropy and Bond Length Alternation in Neutral and Ionized Pyrimidine Bases and Their Model Azines in Vacuo

Abstract

In this review, the complete tautomeric equilibria are derived for disubstituted pyrimidine nucleic acid bases starting from phenol, aniline, and their model compounds—monosubstituted aromatic azines. The differences in tautomeric preferences for isolated (gaseous) neutral pyrimidine bases and their model compounds are discussed in light of different functional groups, their positions within the six-membered ring, electronic effects, and intramolecular interactions. For the discussion of tautomeric preferences and for the analysis of internal effects, recent quantum-chemical results are taken into account and compared to some experimental ones. For each possible tautomer-rotamer of the title compounds, the bond length alternation, measured by means of the harmonic oscillator model of electron delocalization (HOMED) index, is examined. Significant HOMED similarities exist for mono- and disubstituted derivatives. The lack of parallelism between the geometric (HOMED) and energetic (ΔG) parameters for all possible isomers clearly shows that aromaticity is not the main factor that dictates tautomeric preferences for pyrimidine bases, particularly for uracil and thymine. The effects of one-electron loss (positive ionization) and one-electron gain (negative ionization) on prototropy and bond length alternation are also reviewed for pyrimidine bases and their models.

On Some Origins of Tautomeric Preferences in Neutral Creatinine in Vacuo: Search for Analogies and Differences in Cyclic Azoles and Azines

“…However, for the majority of isomeric systems, only the major and some minor isomers can be detected by means of spectroscopic methods (UV, IR, Raman, MW, MS, NMR, etc. ), particularly in the gas phase or solution [1][2][3][4]14,33,36]. Most of the minor isomers cannot be distinguished from the background, and rare isomers are usually undetectable.…”

“…Among various theoretical methods employed in acid-base chemistry, particularly for investigation of proton transfer equilibria, we chose the density functional theory (DFT) method [41] with the three-parameter hybrid exchange functional of Becke [42] and the correlation functional of Lee, Yang, and Parr (B3LYP) [43], and larger basis sets with the diffuse and polarization functions [44] as previously described for tautomeric nucleic acid bases and their model compounds [33,45]. The DFT(B3LYP)/6-311+G(d,p) level of theory has been considered as sufficient to describe quantitatively proton-transfer reactions [46,47].…”

“…This means that delocalization of π-and n-electrons in the cycle is incomplete, and the two isomers do not display an aromatic character. In the case of heterocompounds with the six-membered cycle, such as mono-hydroxy and mono-amino pyridines and pyrimidines, as well as di-substituted pyrimidine nucleic acid bases, tautomers containing the C-sp 3 atom in the ring can only be classified to the family of rare, and even exceptionally rare forms, similarly as those for phenol and aniline [33]. For neutral cyclic azine-derivatives, these tautomers have never been experimentally identified.…”

“…In the literature, one can find some partial results for isolated tautomeric-azoles [2,3,[36][37][38][39], but no general conclusions can be derived. For our examination, we used the same quantum-chemical methods as applied previously for pyrimidine nucleic acid bases and their model aromatic azines [33]. We estimated the stabilities of all possible isomers on the basis of their relative thermochemical parameters.…”

N^N^C-Cyclometalated rhodium(iii) complexes with isomeric pyrimidine-based ligands: unveiling the impact of isomerism on structural motifs, luminescence and cytotoxicity

“…23, Pyrimidine provides researchers with interesting and diverse options for the synthesis of isomeric ligands. 23,[65][66][67][68][69] For example, introducing two different functional groups, e.g. heteroaromatic ones, at the α positions to the nitrogen atoms makes it possible to obtain three families of isomeric ligands (Scheme 1).…”