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. 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).
Tian
Zhixin
Z
Department of Chemistry, The College of William and Mary, Williamsburg, Virginia 23187, USA.
Pawlow
Anna
A
Poutsma
John C
JC
Kass
Steven R
SR
D000143:Acids / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D019905:Benzyl Alcohol / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry; D005583:Fourier Analysis; D005740:Gases; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D013058:Mass Spectrometry; D008968:Molecular Conformation; D021241:Spectrometry, Mass, Electrospray Ionization; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000143:Acids; D000596:Amino Acids; D005740:Gases; D013438:Sulfhydryl Compounds; D006859:Hydrogen; D003903:Deuterium; D003545:Cysteine; D019905:Benzyl Alcohol