Proton affinity of uracil. A computational study of protonation sites

Relative stabilities of uracil tautomers and cations formed by gas-phase protonation were studied computationally with the B3LYP, MP2, QCISD, and QCISD(T) methods and with basis sets expanding from 6-31G(d,p) to 6-311+G(3df,2p). In accordance with a previous density functional theory study, the dioxo tautomer la was the most stable uracil isomer in the gas phase. Gibbs free energy calculations using effective QCISD(T)/6-311+G(3df,2p) energies suggested >99.9% of la at equilibrium at 523 K. The most stable ion isomer corresponded to N-1 protonated 2,4-dihydroxypyrimidine, which however is not formed by direct protonation of la. The topical proton affinities in la followed the order O-8 > O-7 > C-5 > N-3 > N-1. The thermodynamic proton affinity of la was calculated as 858 kJ mol(-1) at 298 K. A revision is suggested for the current estimate included in the ion thermochemistry database. (J Am Soc Mass Spectrom 2000, 11, 1065-1071) (C) 2000 American Society for Mass Spectrometry.