Quantum Chemical Studies of Tautomeric Equilibria in Nucleobases

Quantum chemical investigations have become indispensable for elucidating the tautomeric equilibria of nucleobases, the prototropic isomers that underlie genetic fidelity, mutagenesis and supramolecular recognition. Central to this field is the use of electronic‐structure calculations to map the relative energies, geometric parameters and aromatic character of canonical and rare tautomers in varied environments. Computational protocols, most notably density functional theory, enable systematic evaluation of intramolecular proton transfers, solvent effects and ionization states. These studies reveal how subtle shifts in hydrogen‐bonding networks, ring electron delocalization and external dielectric constants reshape tautomer preferences. Insights from these methods inform our understanding of spontaneous base mispairing, the design of nucleobase analogues in medicinal chemistry and the potential for prebiotic pathways in astrochemical settings. By coupling calculated thermodynamic data with kinetic modelling, researchers now quantify barrier heights for tautomerization, exposing the roles of quantum tunnelling and water mediation at low temperatures. Collectively, quantum chemical studies of nucleobase prototropy not only deepen fundamental knowledge of DNA/RNA chemistry but also guide innovations in biosensing, nucleic acid therapeutics and the search for chemical signatures of life beyond Earth.

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Quantum Chemical Studies of Tautomeric Equilibria in Nucleobases publication trend

The graph below shows the total number of articles in quantum chemical studies of tautomeric equilibria in nucleobases across all publications each year (not limited to Nature Index journals).

Technical terms

Tautomeric equilibrium: A dynamic balance between two or more isomeric forms differing by the position of a proton and a double bond within a molecule.

Prototropy: Intramolecular proton transfer that interconverts tautomers without bond cleavage, often mediated by hydrogen‐bond networks or solvent molecules.

Density functional theory: A quantum mechanical modelling approach that calculates electronic structure and total energy of molecules based on electron density rather than wavefunction.

Aromaticity: A measure of cyclic electron delocalization conferring extra stability to planar ring systems, often quantified by geometric or magnetic criteria.

Reaction barrier: The energy difference between reactants and the transition state, determining the rate at which tautomerization occurs.

References

1. On Prototropy and Bond Length Alternation in Neutral and Ionized Pyrimidine Bases and Their Model Azines in Vacuo. Molecules (2023).
2. Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives. Molecules (2020).
3. Kinetics of direct and water‐mediated tautomerization reactions of nucleobases at low temperatures ⩽200 K. International Journal of Chemical Kinetics (2023).