An accurate prediction of the molecular acidity by employing ab initio or density functional approaches for typical molecular systems is still challenging. Recently, we proposed to utilize two quantum descriptors, molecular electrostatic potential (MEP) and the sum of valence natural atomic orbital (NAO) energies on the nucleus of both the acidic atom and leaving proton, to quantitatively evaluate the pKa values. This new approach has been validated by a number of organic and inorganic systems and justified within the framework of density functional reactivity theory (DFRT). In this work, we apply the approach to building blocks of biological systems, namely, 20 natural α-amino acids and 5 DNA/RNA bases, together with a few other biologically relevant species. Our results show that there exists a strong linear correlation between MEP on the nucleus of the N atom and the sum of N 2p NAO energies, with the correlation coefficient R2 = 0.99. Also, we observe that both MEP on the nitrogen nucleus and the sum of N 2p NAO energies correlate well with experimental pKa values, with the correlation coefficient equal to 0.91. Using this established model, we predicted the trend of pKa changes of amino acids in proteins with different dielectric constants. We also applied the model to predict pKa values for dipeptides. Implications of these linear relationships to understand functions and reactivity of biological systems are discussed as well.
Delivering strong 1H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange
