Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidity, H/D exchange experiments, and computations on cysteine and its conjugate base.

Hydrogen-deuterium exchange experiments were carried out on the conjugate base of cysteine with four different deuterated alcohols. Three H/D exchanges are observed to take place in each case, and a relay mechanism which requires the SH and CO2H groups to have similar acidities and subsequently proceeds through a zwitterionic intermediate is proposed. Gas-phase acidity measurements also were carried out in a quadrupole ion trap using the extended kinetic method and in a Fourier transform mass spectrometer by an equilibrium determination.