Hydrolytic deamination reactions of amidine and nucleobase derivatives

Amidines share the same N=C─N building framework with many essential biochemical substances. In this work, we present a comparative mechanistic study on the deamination reactions of 19 amidine and nucleobase derivatives by the use of density functional theory. All the computations are performed at the B3LYP/6‐31G(d,p) level in the gas phase and with the polarizable continuum model (PCM). Mechanisms of 2‐ and 3‐step pathways including six‐ or eight‐membered ring transition states were explored. Our results show that the overall activation energies for the deamination of amidine derivatives are close to those of nucleobase derivatives of the saturated C5─C6 bond, and lower than those of nucleobase derivatives of the unsaturated C5─C6 bond, while purine derivatives have the highest activation energies among all the derivatives studied. The 3‐step mechanism gives results that are more consistent with the available experimental data than the 2‐step mechanism. Based on the results of our current and previous work, we believe that the 3‐step mechanism is the most likely mechanism for the hydrolytic deamination reactions of amidine and nucleobase derivatives.