motions and asynchronous rehybridizations of the donor and
acceptor (i.e., rehybridization precedes H-tunneling).9–17,19,20
While the 21 KIEs on Xn+ are inflated, those on the alcohol
side are, however, deflated; i.e., 21 b-D6 KIEs on 2-propanol
are close to unity (1.00–1.05), which should be close to the EIE
of 1.52 for an endothermic reaction with a late TS (Table 1).
These elude explanation by the traditional model of H-tunneling
and 11/21 H coupled motions that can only explain the inflated
21 KIEs for H-transfer reactions (see Introduction), but
they can be interpreted by the Marcus-like H-tunneling
model.21,30–36 Within the latter model, the magnitude of the
21 KIE depends upon the extent of the reorganization of the
21 H/D toward the formation of the TRS.36 Thus, both
the deflated (close to unity) 21 KIEs on alcohol and also the
aforementioned inflated (also close to unity) 21 KIEs on Xn+
can be explained in terms of the small degree of reorganization of
21 H/D (equivalent to a small degree of rehybridization) incurred in
forming the TRS. In this context, our observed slightly larger
21 KIE on Hꢀ transfer than on Dꢀ transfer (Table 1) can be
interpreted as due to the relatively longer donor–acceptor tunneling
distance in Hꢀ transfer so that more room is allowed for reorga-
nization resulting in the larger 21 KIE. Note that this explanation
on the basis of the difference in H- and D-tunneling distances has
been successfully used to explain the observed deflated 21 D/T KIE
on alcohol for Dꢀ transfer as compared to the 21 H/T KIE for Hꢀ
transfer in ADH mediated alcohol oxidations.21,36 For example, the
log(kH/kT)H/log(kD/kT)D = 3.26 (superscript (21), subscript (11))
predicted for the classical mechanism was observed to be as large as
10.37 The current explanation is that, in enzymes that are evolved
for the transfer of the most abundant H isotope, the D-transfer
requires shorter tunneling distances, thus inducing crowded/
deformed active sites and decreasing the reorganization of the
21 isotope and the magnitude of the 21 KIE.21,36 It should be
emphasized that while this 11 isotope effect on 21 KIEs was
significant in the ADH systems, it was observed to be very small
or even insignificant (within experimental errors) in our solution
reactions (Table 1). This may be explained in terms of the loose
TRS structures in a less restricted solution medium so that the effect
of tunneling distance of H and D on 21 KIEs is greatly minimized.24
To summarize, kinetics of the hydride transfer reactions from
three aliphatic alcohols to two NAD+ models (PhXn+ and Xn+)
were determined. 21 KIEs on both hydride donors and acceptors
for both hydride transfer and deuteride transfer were determined.
Both of them are close to unity and significantly far from the
corresponding EIEs. 21 KIE on 9-H/D of Xn+ in some systems
are even larger than unity outside of the normal range from
EIE to unity. Moreover, 21 KIEs are slightly larger in hydride
transfer than in deuteride transfer in some systems. These findings
definitely suggest a non-classical hydride tunneling mechanism
involving an imbalanced tunneling ready state where rehybridiza-
tion of both the hydride donor and the acceptor lags behind the
H-tunneling. This is in sharp contrast to the H-tunneling mecha-
nism found in the corresponding enzymatic reactions (e.g., the
ADH reactions) in which rehybridization precedes H-tunneling.
The latter observations in enzymes have been used to suggest
the role of enzyme motions in organizing favorable reaction
geometries for H-tunnelling, which should contribute to the
enzymatic rate enhancement. The findings in this work lend
strong support to this important proposition.
This work was supported by the SIUE’s Seed Grant for
Transitional and Exploratory project (STEP) and the SIUE’s
Undergraduate Research awards (URCA).
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Chem. Commun., 2012, 48, 11337–11339 11339