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

Zhixin Tian, Anna Pawlow, John C. Poutsma, Steven R Kass

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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. The results are in excellent accord with each other and high-level ab initio and density functional theory calculations and indicate that the side-chain thiol in cysteine is more acidic than the carboxyl group by 3.1 kcal mol-1. Deprotonated cysteine is thus predicted to be a thiolate ion. A zwitterionic species also was located on the potential energy surface, but it is energetically unfavorable (+10.1 kcal mol-1).

Original languageEnglish (US)
Pages (from-to)5403-5407
Number of pages5
JournalJournal of the American Chemical Society
Volume129
Issue number17
DOIs
StatePublished - May 2 2007

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