Conversion and Origin of Normal and Abnormal Temperature Dependences of Kinetic Isotope Effect in Hydride Transfer Reactions

Abstract

The effects of substituents on the temperature dependences of kinetic isotope effect (KIE) for the reactions of the hydride transfer from the substituted 5-methyl-6-phenyl-5,6-dihydrophenanthridine (G-PDH) to thioxanthylium (TX(+)) in acetonitrile were examined, and the results show that the temperature dependences of KIE for the hydride transfer reactions can be converted by adjusting the nature of the substituents in the molecule of the hydride donor. In general, electron-withdrawing groups can make the KIE to have normal temperature dependence, but electron-donating groups can make the KIE to have abnormal temperature dependence. Thermodynamic analysis on the possible pathways of the hydride transfer from G-PDH to TX(+) in acetonitrile suggests that the transfers of the hydride anion in the reactions are all carried out by the concerted one-step mechanism whether the substituent is an electron-withdrawing group or an electron-donating group. But the examination of Hammett-type free energy analysis on the hydride transfer reactions supports that the concerted one-step hydride transfer is not due to an elementary chemical reaction. The experimental values of KIE at different temperatures for the hydride transfer reactions were modeled by using a kinetic equation formed according to a multistage mechanism of the hydride transfer including a returnable charge-transfer complex as the reaction intermediate; the real mechanism of the hydride transfer and the root that why the temperature dependences of KIE can be converted as the nature of the substituents are changed were discovered.

Kinetic Isotope Effect of Prostaglandin H Synthase Exhibits Inverted Temperature Dependence

“…On the other hand, only a few examples of KIE increasing with reaction temperature have been published. The non-enzymatic reactions include: (1) the dehydrohalogenation of certain halogen substituted ethylbenzenes [23]; (2) the addition reaction of m-nitro-β,β-difluorostyrene [24]; (3) the reaction between ubiquinol-10 and 5,7-diisopropyltocopheroxyl radical [25]; (4) the proton-coupled electron-transfer (PCET) from ubiquinol to Ru(bpy) 2 (pbim) + (bpy = 2,2'-dipyridyl; pbim = 2-(2-pyridyl)-benzimidazolate) [27]; and (5) the hydride transfer from 5-methyl-6-phenyl-5,6-dihydrophenanthridine (G-PDH) substituted with electron-donating groups to thioxanthylium (TX + ) [26]. All these chemical reactions were conducted in alcohol or acetonitrile.…”

“…Explaining inverted temperature dependence in a KIE is a challenging task and only a few theoretical treatments for single step chemical reactions are available [22,26]. Theoretical analysis of the PCET from ubiquinol to Ru(bpy) 2 (pbim) + indicated that a KIE of inverted temperature dependence in a PCET reaction may arise in a system with proton donor-acceptor motion of high frequency and small inner-space and solvent reorganization energies [22].…”

“…In such a system, when the 0/0 pair of reactant/product vibronic states is in the inverted Marcus region while the 0/1 pair of reactant/product vibronic states is in the normal Marcus region and is the dominant contributor to the overall rate, the free energy barrier is lower for deuterium, giving an increase in KIE with temperature [22]. A theoretical approach based on thermodynamics and kinetics analyses was used to explain the inverted temperature dependence of the KIE for the hydride transfer from G-PDH to TX + [26]. In this case, it was proposed that the hydride transfer from G-PDH to TX + occurs via a two-stage mechanism with two elementary chemical steps: (1) the two reactants approach each other to reversibly form a charge transfer complex that accomplishes partial electron transfer without chemical bond formation or breakage; and (2) hydrogen bearing a partial negative charge transfers irreversibly from the G-PDH-moiety to the TX-moiety [26].…”

“…A theoretical approach based on thermodynamics and kinetics analyses was used to explain the inverted temperature dependence of the KIE for the hydride transfer from G-PDH to TX + [26]. In this case, it was proposed that the hydride transfer from G-PDH to TX + occurs via a two-stage mechanism with two elementary chemical steps: (1) the two reactants approach each other to reversibly form a charge transfer complex that accomplishes partial electron transfer without chemical bond formation or breakage; and (2) hydrogen bearing a partial negative charge transfers irreversibly from the G-PDH-moiety to the TX-moiety [26]. In this case, it was demonstrated that both normal and inverted temperature-dependence of deuterium KIE could be observed in a single reaction.…”

“…In the present study, we found that the activation energies for PGHS-1 or -2 with 10,10,13,13-d 4 -AA (d 4 -AA) are smaller than that for PGHS-1 or -2 with AA and therefore KIEs for PGHS increase with the temperature, showing abnormal, or inverted, temperature dependence. There are only a few reported examples of KIE values increasing with temperature in chemical reactions [23][24][25][26][27] and enzymatic catalyses [16,28].…”