Thiazolium C(2)-proton exchange: structure-reactivity correlations and the pK/sub a/ of thiamin C(2)-H revisited

Journal Article · Tue Jul 12 04:00:00 EDT 1988 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00414a015· OSTI ID:6901515

Washabaugh, M W; Jencks, W P

Rate constants for C(2)-proton exchange from thiamin, N(1')-methylthiamin, and several 3-substituted-4-methylthiazolium ions catalyzed by D/sub 2/O and deuterioxide ion were determined by /sup 1/H NMR at 30/sup 0/C and ionic strength 2.0 M. Values of pK/sub a/ for the thiazolium ions, including thiamin itself, were found to be in the range pK/sub a/ = 17-19; the pK/sub a/ values for N(1')-protonated thiamin and free thiamin C(2)-H in H/sub 2/O are 17.7 and 18.0 respectively. The pK/sub a/ value for N(1')-protonated thiamin was calculated from the observed rate constant for the pD-independent reaction with D/sub 2/O after correction for a secondary solvent deuterium isotope effect of k/sub H/sub 2/O//k/sub D/sub 2/O/ = 2.6. The pK/sub a/ value for free thiamin was calculated from the rate constant for catalysis by OD/sup -/ after correction by a factor of 3.3 = 8/2.4 for an 8-fold negative deviation of k/sub OD/ from the Broensted plot of slope 1.0 for general base catalysis and a secondary solvent isotope effect of k/sub OD//k/sub OH/ = 2.4. Values of k/sub -a/ = 2 x 10/sup 10/ and 3 x 10/sup 9/ M/sup -1/ s/sup -1/ were assumed for diffusion-controlled protonation of the C(2) ylide in the reverse direction by H/sub 3/O/sup +/ and H/sub 2/O, respectively. The Hammett rho/sub I/ value for the exchange reaction catalyzed by deuterioxide ion or D/sub 2/O is 8.4 +/- 0.2. There is no positive deviation of the rate constants for free or N(1')-substituted thiamin analogues in either Hammett correlation. This shows that the aminopyrimidinyl group does not provide significant intramolecular catalysis of nonenzymic C(2)-proton removal in the coenzyme.

• Research Organization: Brandeis Univ., Waltham, MA (USA)
• OSTI ID: 6901515
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:14; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AZOLES
BARYONS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MODELS
CARBON 13
CARBON ISOTOPES
CATALYSIS
ELEMENTARY PARTICLES
ENZYMES
EVEN-ODD NUCLEI
FERMIONS
HADRONS
HEAVY WATER
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPES
ISOTOPIC EXCHANGE
KINETICS
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PROTONS
REACTION KINETICS
RESONANCE
STABLE ISOTOPES
THIAZOLES
WATER