The gas-phase acidity and proton affinity of nucleobases that are substrates for the enzyme human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) have been examined using both theoretical and experimental methods. These thermochemical values have not heretofore been measured and provide experimental data to benchmark the computational results.HGPRT is important for human health and is also a key target for antiparasitic chemotherapy. We use our gas-phase results to lend insight into the HGPRT mechanism and also propose kinetic isotope studies that could potentially differentiate between possible mechanisms.

In this review, we discuss gas phase experimentation centered on the measurement of acidity and proton affinity of substrates that are useful for understanding catalytic mechanisms. The review is divided into two parts. The first covers examples of organocatalysis, while the second focuses on biological catalysis. The utility of gas phase acidity and basicity values for lending insight into mechanisms of catalysis is highlighted.