Protein structural effects on the temperature (T) dependence of kinetic isotope effects (KIEs) in H-tunneling
reactions
have recently been used to discuss about the role of enzyme thermal
motions in catalysis. Frequently observed nearly T-independent KIEs in the wild-type enzymes and T-dependent KIEs in variants suggest that H-tunneling in the former
is assisted by the naturally evolved protein constructive vibrations
that help sample short donor–acceptor distances (DADs) needed.
This explanation that correlates the T-dependence
of KIEs with DAD sampling has been highly debated as simulations following
other H-tunneling models sometimes gave alternative explanations.
In this paper, solvent effects on the T-dependence
of KIEs of two hydride tunneling reactions of NADH/NAD+ analogues (represented by ΔE
a = E
aD – E
aH)
were determined in attempts to replicate the observations in enzymes
and test the protein vibration-assisted DAD sampling concept. Effects
of selected aprotic solvents on the DADPRC’s of
the productive reactant complexes (PRCs) and the DADTRS’s of the activated tunneling ready states (TRSs) were obtained
through computations and analyses of the kinetic data, including 2°
KIEs, respectively. A weaker T-dependence of KIEs
(i.e., smaller ΔE
a) was found in a more polar aprotic solvent in which the system has
a shorter average DADPRC and DADTRS. Further
results show that a charge-transfer (CT) complexation made of a stronger
donor/acceptor gives rise to a smaller ΔE
a. Overall, the shorter and less broadly distributed DADs resulting
from the stronger CT complexation vibrations give rise to a smaller
ΔE
a. Our results appear to support
the explanation that links the T-dependence of KIEs
to the donor–acceptor rigidity in enzymes.
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