Racemization rates, effects

Bada, J. L., Shou, M., Effects of various environmental parameters on amino acid racemization rates in fossil bones, Geological Soc. America, Abstracts with Programs, 8, 762-763... 

AS -8 to +4 e.u. Even though the racemization rate constants differ slightly, their distinct dependence on the steric and to a lesser extent on the electronic effects of the substituents bonded to the sulfinyl sulfur atom was noted. It deserves adding that the activation volume for racemization of methyl p-tolyl sulfoxide 41, A F 0 ml/mol, is also consistent with the pyramidal inversion mechanism (249). 

Fujiwara and Yamamoto have studied the racemization of anhydrous compounds of the type [M(phen)3]X2 and [M(bipy)3]X2 where M = Fe or Ni and X = Cl-, Br-, I- or C104-.26 The rates of racemization of the nickel compounds were found to depend on the identity of the anion racemization rates for the iron compounds were anion-independent. However, the kinetic analysis has been called into question.27 28 If valid, the kinetic anion effect for the nickel compounds follows an order that is opposite that found by Kutal and Bailar23 for the racemization of [Co(en)3]X3 salts C104 < I- < Br- < Cl . It was proposed25 that the iron compounds racemize by a twist mechanism and that the nickel compounds racemize by nucleophilic attack by lattice anions to form a seven-coordinate transition state. 

Steric isotope effects are well documented in the literature of organic chemistry, and have been measured in several reactions in which severe crowding occurs. Mislow and co-workers first demonstrated such effects by determining racemization rates of I, where R = H or D [92], The inverse... 

Fig. 26 A Chiral memory effect applied to the construction of a chiral softball homo-dimeric capsule made of achiral units. B Racemic softball binds a chiral guest leading preferentially to one diastereoisomer. Fast exchange, compared to capsule s racemization rate, with a better achiral guest allows preparation of enantioenriched capsule...

The effects of pH on racemization rates of free amino acids in aqueous solution are complex (21). However, when bone fragments were heated at 100°C in solutions of pH 2-9, the rate constant for aspartic acid racemization was essentially independent of pH (37). It was proposed that the phosphate from the bone s inorganic phase acts as a buffer. This same buffering action would take place in a bone under natural conditions of burial as well. 

In support of the equilibrium displacement mechanism, a study of the Pfeiffer rotation of the system D, L-[ Ni ( o-phen) 3] 2+ with levo-malic acid as an environment substance in water produces some interesting results (Figure 2). The Pfeiffer Effect reaches its maximum in just over k days, and if, at that time, exactly as much dextro-malic acid is added to the system as the levo enantiomer already present, then this has the effect of removing (deactivating) the environment substance, so that the excess of the complex enatiomer has no alternative but to undergo racemization. It should be noted (Figure 3) that the rate of this racemization is identical to the racemization rate of the optically pure complex which has been resolved by conventional means. 

From reports in the early literature resting cell bioconversions of hydantoin derivatives, which do not racemize with high velocities, indicated an enzymatic racemization and the presence of a hydantoin racemase. In addition, the chemical and the enzymatic racemization proceed via the keto-enol tautomerism, which is shown in Fig. 12.4-20. Stabilizing effects on the enolate structure such as electronegative substituents are responsible for the velocity of the racemization12, 71. Increased racemization rates can be also seen at more alkaline pH-values and with increased temperatures[71. 

FIGURE 6.4 (See color insert following page 40). Solvent effect on the racemization rate. 

The racemic rate was low and the enantioselective rate very fast (like Pt). There is, however, a curious particle size effect. If the Ir particles are made bigger by increasing the Ir loading but keeping the calcination temperature constant, then the optical yield and the reaction rate both increase. 

Hoffmann and coworkers have observed a marked steric effect on the racemization rate of a-lithiated sulfides, selenides and tellurides branched, bulky substituents on the heteroatom increase the configurational stability (Fig. 9) [27, 29]. These results imply that the rotation about the C-X bond (Fig. 8) should be the rate-determining step of racemization [27]. Reich and coworker have also demonstrated a similar conclusion by H-NMR analyses and kinetic studies [30]. Furthermore, they confirmed that the racemization rate of a-thio carban-... 

The effect of different counteranions, X, on the rate of racemization of [Ni(phen)3] + ion has been investigated in H20-Bu 0H mixtures. When the mole fraction of Bu OH is greater than 0.5, X" ions accelerate the racemization rate in the order CIO " < 1 < Br < Cl". Attack by X" at the metal ion rather than the 2- or 4-positions of phen (analogous to the Gillard mechanism) is postulated to be involved, primarily because Cl" ion is a better accelerating anion than I" ion and the reverse behaviour would be expected if attack at the aromatic ring were involved. ... 

In aquation of the cations [M(NH3)5Br] + (M = Cr or Co) in alcohol-water mixtures, solvent composition variation has much more effect on A.S than on iiH. This is attributed to solvation-shell ordering effects in the transition state. Enhancement of reactivity in the reaction of cobalt(ii) with chlorophyllic acid in methanol on addition of lithium nitrate is attributed to inhibition of transition-state solvation. The effective radius of a transition state can be guessed from the variation of rate constant with dielectric constant. This approach has been used for the bromide-bromate reaction. In contrast to this concentration of attention on the transition state, it may be noted that it is the stabilization of the reactant in relation to water structure that is thought to control the variation of the racemization rate of the ( + )-[Co(phen)3] + cation in t-butyl alcohol-water mixtures. ... 

Data derived by Dwyer on the ratio of the rate constants (kjki) has been criticized by Harris since the values used by Dwyer for the rotation at the end of the racemization of d-[Ni(phen)3] were those obtained immediately after adding the optically active ion to the racemic mixture of the complex in solution. The ratio thus was not the equilibrium rotation. It was not reasonable, according to Harris, to use the data in support of an equilibrium theory for the Pfeiffer effect. Contradictory results are reported by Craddock and Jones in that no difference was found for the racemization rates for either isomer (e.g., d- or /-[Ni(phen)3] ) if the complex is in the presence of an optically active species. These authors point out that another environmental factor, temperature, could have accounted for unusual or anomalous rotations previously found. It is evident that something more than an equilibrium shift or a configurational activity is needed to explain Pfeiffer rotations. 

The configurational activity concept is not in keeping with the time-rotation study of the present authors as well as Pfeiffer s own studies on the system [Ni(phen)3](BCS)2. Since the racemization rate of the nickel(II) complex is slow, any shift in the equilibrium of the d- and /-isomers of the complex should also be slow. The Pfeiffer effect for this complex would be expected to increase from a zero value to a maximum. The observed data shows an instantaneous increase (vide supra) that is about 46% of the final rotation. Although from this study an equilibrium shift may be operative it cannot be the only effect. 

Many investigators have studied substitution at iron(II)-diimine complexes in binary aqueous mixed solvents and other investigators in aqueous salt solutions. Some years ago the results of addition of salts and a cosolvent were assessed, for [Fe(5N02phen)3] in water, t-butyl alcohol, acetone, dimethyl sulfoxide, and acetonitrile mixtures containing added potassium bromide or tetra-n-butylammonium bromide. " Now the effects of added chloride, thiocyanate, and perchlorate on dissociation and racemization rates of [Fe(phen)3] in water-methanol mixtures have been established. The main explanation is in terms of increasing formation of ion pairs as the methanol content of the medium increases, but it is somewhat spoiled by the (unnecessary) assumption of a mechanism involving interchange within the ion pairs. Kip values (molar scale) of 11,18, and 25 were estimated for perchlorate, chloride, and thiocyanate in 80% (volume) methanol at 298.2 K. These values may be compared with values of 20, 7, and 4 for association between [Fe(phen)3] and iodide, " [Fe(bipy)3] and iodide, " and [Fe(phen)3] and cyanide " " in aqueous solution (at 298.2,... 

It is also possible to extract dynamic information concerning racemization rates through measurement of steady-state CPL. Again neglecting time-dependent orientational effects, one may integrate Equations [26] and [27] over long times (0 °o) and obtain the following result... 

The experimental data state that [6]helicene 2 having six alkoxy substituents racemizes considerably slower than the parent [6]helicene 1. Hence, we can conclude that the electron-donating ability of oxygen substituents should not be responsible for the increase in the racemization rates observed for compounds 3 and 4 regarding to 1. We can discard the electronic effect of the substituents as the origin of the acceleration in the racemization process. 

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