H/D isotope effects

In the H/D isotope effect case, m2/wi = 2, the interval of temperatures between re(H) and re(D) is wider than AT as predicted by (2.19), and in this interval the H atom tunnels while the D atom classically overcomes the barrier. For this reason the isotope effect becomes several orders larger than that described by (2.70). At 7" < 7 c(m2) the tunneling isotope effect becomes independent of the temperature. 

These experiments demonstrate the importance of proton transfer processes during hole transfer through DNA. S. Steenken has already remarked that a proton shift between the G C bases stabilizes the positive charge [23]. If such a proton shift is coupled with the hole shift, a deuterium isotope effect should arise. Actually, H/D isotope effects are described by V. Shafiro-vich, M.D. Sevilla as well as H.H. Thorp in their articles of this volume. Experiments with our assay [22] also demonstrate (Fig. 16) that hole transfer in protonated DNA (H20 as solvent) is three times more efficient than in deuterated DNA (D20 as solvent). If this reflects a primary isotope effect, it shows that the charge transfer is coupled with a proton transfer. 

Warshel is to utilize a formula identical to (11.22) in this chapter to compute the free energy change. They employed an empirical valence bond (EVB, below) approach to approximately model electronic effects, and the calculations included the full experimental structure of carbonic anhydrase. An H/D isotope effect of 3.9 1.0 was obtained in the calculation, which compared favorably with the experimental value of 3.8. This benchmark calculation gives optimism that quantum effects on free energies can be realistically modeled for complex biochemical systems. 

That eh is the intermediate species and not the H atom has been verified by adding NzO and methanol to water then, N2, not H2, is the principal product. Alkali and alkaline earth metals above Na in the electrochemical series will also generate eh on dissolution in water. Moreover the H/D isotope effect in water containing 50% D is consistent with the reaction 2eh—H2 + 20H (Anbar and Meyerstein, 1966 Hart and Anbar, 1970). 

Other interesting data in these reactions concern the H/D isotopic effect of the nucleophile/catalyst, for example when [2-hydroxypyridine] = [2 — 02H] = 0.08, fcobsH/ obsD = 1-5. Since a very poor H/D effect is usual in SjvAr reactions with neutral nucleophiles (amines) in apolar solvents10, the authors conclude that the unusually high H/D effect should be due to a difference in the Xh/Xd = 1.75 of the molecular complex. Nevertheless, the same effect could be explained on the basis of an autoassociation of... 

Taking into account, for instance, the slight differences in K observed for l-fluoro-2,4,6-trinitrobenzene and 1 -chloro-2,4,6-trinitrobenzene in Table 13, it is difficult to explain such a difference in K /K. Nevertheless, a H/D isotopic effect of 1.5 could be easily explained... 

Table 6.3 lists a few H/D isotope effects (kH/kD) for some of the examples listed in Table 6.2. It is noted with some regret that the errors in the isotope effects (kH/kD) calculated by ICVT/ p,OMT are about the same as the errors reported for kH in Table 6.1. One might have hoped to see some cancellation of error when calculating isotope effects.

FLF)- (L = H or D) anion in low temperature solutions of (C4H9)4N+ (FL)nF . The authors were able to determine zero-, one-, and two-bond, H/D isotope effects on hydrogen and fluorine NMR chemical shifts for the series n = 1 to n = 3, and to relate the observed spectra to H/D isotope effects on the hydrogen bond geometries. Isotope effects on spin-spin L-F and F-F coupling 13C constants were reported. 

H/D Isotope Effects and Small Angle Neutron Scattering... 

For historic and practical reasons hydrogen isotope effects are usually considered separately from heavy-atom isotope effects (i.e. 160/180, 160/170, etc.). The historic reason stems from the fact that prior to the mid-sixties analysis using the complete equation to describe isotope effects via computer calculations was impossible in most laboratories and it was necessary to employ various approximations. For H/D isotope effects the basic equation KIE = MMI x EXC x ZPE (see Equations 4.146 and 4.147) was often drastically simplified (with varying success) to KIE ZPE because of the dominant role of the zero point energy term. However that simplification is not possible when the relative contributions from MMI (mass moment of inertia) and EXC (excitation) become important, as they are for heavy atom isotope effects. This is because the isotope sensitive vibrational frequency differences are smaller for heavy atom than for H/D substitution. Presently... 

Some examples of small molecule dipole moment H/D isotope effects are given in Table 12.1. These typically vary from 1 to 10 or more milli-Debyes. A qualitative... 

Van Hook, W. A. and Wolfsberg, M., Comments on H/D isotope effects on polarizabilities. Correlation with virial coefficient, molar volume and electronic second moment isotope effects. Z Naturforsch. 49A, 563 (1994)... 

Equation 14.39 is relatively simple for a secondary isotope effect because neither E nor E is expected to be isotope dependent for 3-H/D isotope effects. To illustrate, Rabinovitch and Setzer (reading list) considered 2,3 C-C bond rupture of n-perprotiobutane and 1,4 ditrideutero-n-butane... 

It may have been the dramatic 1964 publication of E.S. Lewis and L. Funderburk that forced the question of hydrogen tunneling in complex solution reactions near room temperature into the consciousness of a larger scientific public, particularly in physical-organic chemistry. This article presented isotope effects for proton abstraction from 2-nitropropane by a series of substituted pyridines, and the values rose sharply as the degree of steric hindrance to the reaction increased (Fig. 1). AU the observed H/D isotope effects, from 9.6 to 24, were larger than expected from the simplest version of the so-called semiclassical theory of isotope effects (Fig. 2). 

Fig. 2.18. Observation of secondary H/D isotope effects on the a-cleavage of tertiary amine molecular ions. For convenience, m/z labels have been added to the original energy scale of the MIKE spectmm. Adapted from Ref. [78] with permission. American Chemical Society, 1988.

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

K. R. Boyles, S.M. Chajkowski, R.S. Disselkamp, C.H.F. Peden A Cavitating Ultrasound Study of the H/D Isotope Effect in the Hydrogenation of Aqueous... 

Cl and C2 are unequal. However, the larger isotope effect at Cl implies more advanced binding at this carbon atom in the transition state (19). Note too the inverse ot-secondary ( h/ d) isotope effects at the hydrogens bonded to Cl and C2. These carbons rehybridize from sp toward sp as the addition proceeds, so that h/ d < 0 is expected. The greater effect at H-C versus H-C2 is also consis tent with greater carbene binding to the alkene s terminal C in the transition state. 

The decomposition of the reduced complex is facilitated, most probably, by an electrophilic substitution of I+ by H+. This is a relatively fast step, as no add catalysis or H-D isotope effect could be demonstrated. The presence of Cu(I) in a favorable position close to the iodine atom facilitates the reduction of the ligand. 

The C—H bond is broken at a faster rate than is the stronger C—D bond. The ratio of the rate constants, measures this H-D isotope effect. The observation of an isotope effect indicates... 

These are both E2 reactions in which the C—H or C—D bonds are broken in the rate-controlling step. Therefore, the H-D isotope effect accounts for the faster rate of reaction of CH3CH2I. 

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