Prediction of Kinetic Isotope Effects for Various Hydride Transfer Reactions Using a New Kinetic Model.

In this work, kinetic isotope effect (KIEself) values of 68 hydride self-exchange reactions, XH(D) + X(+) → X(+) + XH(D), in acetonitrile at 298 K were determined using a new experimental method. KIE values of 4556 hydride cross transfer reactions, XH(D) + Y(+) → X(+) + YH(D), in acetonitrile were estimated from the 68 determined KIEself values of hydride self-exchange reactions using a new KIE relation formula derived from Zhu's kinetic equation and the reliability of the estimations was verified using different experimental methods. A new KIE kinetic model to explain and predict KIE values was developed according to Zhu's kinetic model using two different Morse free energy curves instead of one Morse free energy curve in the traditional KIE theories to describe the free energy changes of X-H bond and X-D bond dissociation in chemical reactions. The most significant contribution of this paper to KIE theory is to build a new KIE kinetic model, which can be used to not only uniformly explain the various (normal, enormous and inverse) KIE values but also safely prodict KIE values of various chemical reactions.

A classical but new kinetic equation for hydride transfer reactions.

A classical but new kinetic equation to estimate activation energies of various hydride transfer reactions was developed according to transition state theory using the Morse-type free energy curves of hydride donors to release a hydride anion and hydride acceptors to capture a hydride anion and by which the activation energies of 187 typical hydride self-exchange reactions and more than thirty thousand hydride cross transfer reactions in acetonitrile were safely estimated in this work. Since the development of the kinetic equation is only on the basis of the related chemical bond changes of the hydride transfer reactants, the kinetic equation should be also suitable for proton transfer reactions, hydrogen atom transfer reactions and all the other chemical reactions involved with breaking and formation of chemical bonds. One of the most important contributions of this work is to have achieved the perfect unity of the kinetic equation and thermodynamic equation for hydride transfer reactions.

Conversion and origin of normal and abnormal temperature dependences of kinetic isotope effect in hydride transfer reactions.

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.

What are the differences between ascorbic acid and NADH as hydride and electron sources in vivo on thermodynamics, kinetics, and mechanism?

Ascorbic acid (AscH(2)) and dihydronicotinamide adenine dinucleotide (NADH) are two very important natural redox cofactors, which can be used as hydride, electron, and hydrogen atom sources to take part in many important bioreduction processes in vivo. The differences of the two natural reducing agents as hydride, hydrogen atom, and electron donors in thermodynamics, kinetics, and mechanisms were examined by using 5,6-isopropylidene ascorbate (iAscH(-)) and ß-D-glucopyranosyl-1,4-dihydronicotinamide acetate (GluNAH) as their models, respectively. The results show that the hydride-donating ability of iAscH(-) is smaller than that of GluNAH by 6.0 kcal/mol, but the electron-donating ability and hydrogen-donating ability of iAscH(-) are larger than those of GluNAH by 20.8 and 8.4 kcal/mol, respectively, which indicates that iAscH(-) is a good electron donor and a good hydrogen atom donor, but GluNAH is a good hydride donor. The kinetic intrinsic barrier energy of iAscH(-) to release hydride anion in acetonitrile is larger than that of GluNAH to release hydride anion in acetonitrile by 6.9 kcal/mol. The mechanisms of hydride transfer from iAscH(-) and GluNAH to phenylxanthium perchlorate (PhXn(+)), a well-known hydride acceptor, were examined, and the results show that hydride transfer from GluNAH adopted a one-step mechanism, but the hydride transfer from iAscH(-) adopted a two-step mechanism (e-H(•)). The thermodynamic relation charts (TRC) of the iAscH(-) family (including iAscH(-), iAscH(•), iAsc(•-), and iAsc) and of the GluNAH family (including GluNAH, GluNAH(•+), GluNA(•), and GluNA(+)) in acetonitrile were constructed as Molecule ID Cards of iAscH(-) and of GluNAH in acetonitrile. By using the Molecule ID Cards of iAscH(-) and GluNAH, the character chemical properties not only of iAscH(-) and GluNAH but also of the various reaction intermediates of iAscH(-) and GluNAH all have been quantitatively diagnosed and compared. It is clear that these comparisons of the thermodynamics, kinetics, and mechanisms between iAscH(-) and GluNAH as hydride and electron donors in acetonitrile should be quite important and valuable to diagnose and understand the different roles and functions of ascorbic acid and NADH as hydride, hydrogen atom, and electron sources in vivo.

Actual structure, thermodynamic driving force, and mechanism of benzofuranone-typical compounds as antioxidants in solution.

5,7-Ditert-butyl-3-(3,4-dimethylphenyl)benzofuran-2(3H)-one (HP-136) (1H) and its 30 analogues (2H-5H) as benzofuranone-typical antioxidants were synthesized. The structures of the benzofuranones in solid and solution were examined by using experimental and theoretical methods. The results show that the dominant structure is the lactone form rather than the enol form both in solid and solution. The thermodynamic driving forces of the 31 benzofuranone-typical compounds to release protons [ΔG(PD)(XH)], hydrogen atoms [ΔG(HD)(XH)], and electrons [E(ox)(XH)] and the thermodynamic driving forces of the anions (X(-)) of the benzofuranones to release electrons [E(ox)(X(-))] were determined for the first time in DMSO. The ΔG(HD)(XH) scale of these compounds in DMSO ranges from 65.2 to 74.1 (kcal/mol) for 1H-4H and from 73.8 to 75.0 (kcal/mol) for 5H, respectively, which are all smaller than that of the most widely used commercial antioxidant BHT (2,6-ditert-butyl-4-methylphenol, 81.6 kcal/mol), suggesting that the 31 XH could be used as good hydrogen-atom-donating antioxidants. The ΔG(PD)(XH) were observed to range from 11.5 to 16.0 (kcal/mol) for 1H-4H and from 18.6 to 22.4 (kcal/mol) for 5H, indicating that benzofuranones (1H-4H) are good proton donors, and their analogues (5H) should belong to middle-strong proton donors. E(ox)(XH) of the 31 XH to release an electron vary from 1.346 to 1.962 (V versus Fc(+/0)), implying that the 31 XH are weak electron donors, whereas the quite negative E(ox)(X(-)) show that X(-) are good electron donors. The Gibbs free-energy changes of the radical cations (XH(+•)) to release protons [ΔG(PD)(XH(+•))] were evaluated according to the corresponding thermodynamic cycle, and the results reveal that XH(+•) are good proton donors. Further inspection of our experimental results showed the ΔG(HD)(XH), ΔG(PD)(XH), ΔG(PD)(XH(+•)), E(ox)(XH), and E(ox)(X(-)) of the five chemical and electrochemical processes are all linearly dependent on the sum of Hammett substituent parameters σ with very good correlation coefficients, indicating that for any one- or multisubstituted species at the para- and/or meta-position of benzofuranones and their various reaction intermediates, the five thermodynamic driving force parameters all can be easily and safely estimated from the corresponding Hammett substituent parameters. The rates of hydrogen atom transfer from XH to DPPH(•) were determined by using the UV-vis absorption spectroscopy technique. Combining these important thermodynamic parameters and dynamic determination results, the mechanism of hydrogen transfer from HP-136 and its analogues to DPPH(•) was studied. The results suggest that the hydrogen transfer from HP-136 and its analogues 2H to DPPH(•) actually includes two steps, proton transfer and the following electron transfer, but the proton transfer is rate-determined.