Insights into nucleic acid reactivity through gas-phase experimental and computational studies

Accurate measurements of the acidities and basicities of nucleic bases and nucleic base derivatives is essential for understanding issues of fundamental importance in biological systems. Hydrogen bonding modulates recognition of DNA and RNA bases, and the interaction energy between two bonded complementary nucleobases is dependent on the intrinsic basicity and acidity of the acceptor and donor groups. In addition, understanding the intrinsic reactivity of nucleic bases can shed light on key biosynthetic mechanisms for which nucleobases are substrates. In this review, we highlight advances in our lab toward understanding the fundamental reactivity of DNA and RNA. In particular, we focus on our investigation of the gas phase acidities and basicities of natural and unnatural nucleobases, and the implications of our results for the mechanisms of nucleotide biosynthetic and repair enzymes.