%0 Journal Article
%A DuPré, Donald B.
%A Wong, John L.
%D 2007
%T Thiamin Deprotonation Mechanism. Carbanion Development Stabilized by the LUMOs of
Thiazolium and Pyrimidylimine Working in Tandem and Release Governed by a H-Bond
Switch
%U https://acs.figshare.com/articles/journal_contribution/Thiamin_Deprotonation_Mechanism_Carbanion_Development_Stabilized_by_the_LUMOs_of_Thiazolium_and_Pyrimidylimine_Working_in_Tandem_and_Release_Governed_by_a_H_Bond_Switch/3017347
%R 10.1021/jp067308i.s001
%2 https://acs.figshare.com/ndownloader/files/4718659
%K iminopyrimidine tautomeric form
%K thiamin electron
%K NBO analysis
%K sulfur acts
%K CMO
%K LUMO
%K azolium models
%K pyrimidylimine systems
%K thiamin diphosphate
%K HOMO
%K QTAIM topological
%K MO decomposition
%K Pyrimidylimine Working
%K NMR
%K C 2 proton
%K Carbanion Development Stabilized
%K thiamin modeling
%K C 2 carbanion
%K azolium analogs
%K Thiamin Deprotonation Mechanism
%K transition state
%K quantum theory
%K thiamin carbanion
%X Our previous paper (J. Phys. Chem. A 2005, 109, 7606) using computed atomic charges, based on the quantum
theory of atoms in molecules (QTAIM), on azolium models of thiamin diphosphate has shown that only
sulfur acts as an effective electron sink in the formation of the thiamin carbanion intermediate. Herein we
apply natural bond orbital (NBO) theory to the analysis of orbital contributions to canonical molecular orbitals
(CMOs) of six abbreviated azolium analogs of the carbanion to better understand the unique function of
sulfur. The NBO/CMO data provide a description of the origin of the first thiamin electron sink: sulfur
performing in the σ- and π-orbitals of the transition state as well as in the carbanion, and its advantages due
to low electronegativity and moderate size. At the next level of thiamin modeling, we include the six-membered
pyrimidine ring to represent the prerequisite V-structure in the iminopyrimidine tautomeric form. This model
is subjected to incremental deprotonation and MO decomposition. The 4‘-pyrimidylimine moiety, in addition
to being an internal base to abstract the C2 proton, also performs as the second electron sink. Thus, the
LUMOs of the thiazolium and pyrimidylimine systems working in tandem stabilize the developing charges
in these transient structures, with facilitation from their HOMOs. Further, the absence of detectable amounts
of the C2 carbanion in 13C2-labeled thiamin−enzyme complex by NMR is explained. Both NBO analysis
and the QTAIM topological electronic properties suggest the operation of a H-bonding scheme that leads to
the formation of a cryptic C2 carbanion that is not accumulated. The shielding of the carbanion by the N4‘−H
hydrogen bond is weakened by N1‘−H deprotonation. Consequently, prior return of the N1‘ proton to the
nearby glutamate may be the switch for streaming a timed-release of the unstable C2 carbanion to the incoming
substrate.
%I ACS Publications