A mechanistic probe for asymmetric reactions: deuterium isotope effects at enantiotopic groups

The development of a mechanistic probe that is especially suitable for the study of asymmetric reactions is presented. Chemically innocuous enantiotopic methyl groups are utilized as probes for the distinct environments that develop at the transition state for the (-)-B-chlorodiisopinocampheylborane reduction of 4'-methylisobutyrophenone. 2H kinetic isotope effects (KIEs) are determined for both enantiotopic methyl groups using two types of competition reactions. One competition is that between the d3-methyl enantiomeric isotopomers. The other competition reaction is that between the d6-dimethyl and perprotiated isotopologues. The rate constant ratios can be converted into kinetic isotope effects upon each of the individual enantiotopic methyl groups by invoking the rule of the geometric mean. The resulting isotope effect measurements yield highly precise values and contribute further understanding to the transition structure for this stereoselective reduction. The results are discussed in the context of steric isotope effects and the origins of these effects, which arise from the impact of steric crowding upon the anharmonicity of C-H bonds in the transition structure relative to the reactant state.     

Nonadditivity of secondary deuterium isotope effects on basicity of trimethylamine

Secondary deuterium isotope effects (IEs) on basicities of isotopologues of trimethylamine have been accurately measured by an NMR titration method applicable to a mixture. Deuteration definitely increases the basicity, by approximately 0.021 in the Delta pK per D. The IE is attributed to the lowering of the CH stretching frequency and zero-point energy by delocalization of the nitrogen lone pair into the C-H antibonding orbital. Because this depends on the dihedral angle between the lone pair and the C-H, a further consequence is a preference for conformations with H antiperiplanar to the lone pair and D gauche. This leads to a predicted nonadditivity of IEs, which is confirmed experimentally. It is found that the decrease in basicity, per deuterium, increases with the number of deuteriums. The nonadditivity of IEs is a violation of the widely assumed Rule of the Geometric Mean.     

Substituent effects in pericyclic reactions of radical cations: the ring opening of 3-substituted cyclobutene radical cations

The substituent effects on the ring-opening reaction of cyclobutene radical cations have been studied at the Becke3LYP/6-31G* level of theory. The effect on the reaction energies and activation energies of the concerted and stepwise pathways of electron-donating substituents such as methyl and methoxy as well as electron-withdrawing substituents such as nitrile and carboxaldehyde in the 3-position of the cyclobutene is discussed. The exothermicity of the reaction correlates well with the ability of the substituent to stabilize the 1,3-butadiene radical cation by electron donation or conjugation. The relative stability of the (E) and (Z) isomers of the resulting 1,3-butadiene radical cations depends largely on steric effects. Similarly, steric effects are responsible for the relative energies of the different diastereomeric transition structures. The cyclopropyl carbinyl intermediate of the stepwise pathway resembles the nonclassical carbocation and is stabilized by electron-donating substituents. In the case of electron-donating substituents, this species becomes a minimum on the potential energy hypersurface, whereas unstabilized or destabilized cyclopropyl carbinyl radical cations are not minima on the hypersurface. The stabilization of the cyclopropyl carbinyl radical cation by substituents correlates qualitatively with the Brown-Okamoto substituent parameter sigma+. However, in all cases studied here, the concerted mechanism is the lowest energy pathway.     

The effect of conjugation on the magnitude of secondary alpha deuterium kinetic isotope effects

The unexpectedly small secondary alpha deuterium KIE in the 4-methoxybenzyl chloride-thiophenoxide ion reaction is attributed to the increased conjugation between the aryl group and the alpha carbon in the S_N2 transition state.     

Metal-catalyzed phosphodiester cleavage: secondary 18O isotope effects as an indicator of mechanism

Information about the transition states of metal-catalyzed hydrolysis reactions of model phosphate compounds has been obtained through determination of isotope effects (IEs) on the hydrolysis reactions. Metal complexation has been found to significantly alter the transition state of the reaction from the alkaline hydrolysis reaction, and the transition state is quite dependent on the particular metal ion used. For the diester, ethyl p-nitrophenyl phosphate, the nonbridge 18O effect for the hydrolysis reactions catalyzed by Co(III) 1,5,9-triazacyclononane and Eu(III) were 1.0006 and 1.0016, respectively, indicative of a slightly associative transition state and little net change in bonding to the nonbridge oxygen. The reaction catalyzed by Zn(II) 1,4,7,10-tetraazacyclododecane had an 18O nonbridge IE of 1.0108, showing the reaction differs significantly from the reaction of the noncomplexed diester and resembles the reactions of triesters. Reaction with Co(III) 1,4,7,10-tetraazacyclododecane showed an inverse effect of 0.9948 reflecting the effects of bonding of the diester to the Co(III). Lanthanide-catalyzed hydrolysis has been observed to have unusually large 15N effects. To further investigate this effect, the 15N effect on the reaction catalyzed by Ce(IV) bis-Tris propane solutions at pH 8 was determined to be 1.0012. The 15N effects were also measured for the reaction of the monoester p-nitrophenyl phosphate by Ce(IV) bis-Tris propane (1.0014) and Eu(III) bis-Tris propane (1.0012). These smaller effects at pH 8 indicate that a smaller negative charge develops on the nitrogen during the hydrolysis reaction.     

A computational study of remote C-H activation by amine radical cations: implications for the photochemical reduction of carbon dioxide

A computational study, using density functional theory calibrated against higher-level methods, has been undertaken to evaluate tertiary amines whose radical cations might lose hydrogen atoms from positions other than the alpha carbons. The purpose was to find photochemically activated reducing agents for carbon dioxide that could be regenerated in a separate photochemical reaction. The calculations have revealed two reactions that might be suitable for this purpose. In one, the nitrogen of the radical cation makes a bond to a remote carbon with simultaneous displacement of a hydrogen atom. In the other, a remote hydrogen atom is transferred to the nitrogen, thereby creating a distonic radical cation that can lose a hydrogen atom beta to the radical site. The latter reaction is found to be particularly favorable since it apparently involves a surface crossing that allows the amine radical cation and CO2 radical anion to transform smoothly to a ground-state formate ion and an alkene. A number of structural motifs are investigated for the amines. The lower ionization potential of aromatic amines, compared to their aliphatic analogues, is desirable in that it could permit the use of longer wavelength light to drive the reaction. However, a thermochemical cycle shows that the reduction in ionization potential must be matched by an increase in proton affinity of the amine if the intramolecular hydrogen transfer is to be exothermic. Most aromatic amines do not satisfy this criterion and, hence, would have to rely on the displacement reaction for hydrogen-atom release if they were to be used as renewable reagents for CO2 reduction. Examples of specific aromatic and aliphatic tertiary amines that should be suitable for the purpose are presented, and their relative merits and weaknesses are discussed.     

BEBO calculations of kinetic isotope effects for methyl radical reactions with alkanes and ketones

Kinetic isotope effects for hydrogen abstraction reactions of methyl radicals with methane, ethane, propane, acetone, butanone-2, pentanone-3 and biacetyl have been calculated using the BEBO method, considering recent values for the Pauling constant and the noble gas parameters. The results were compared with the experimental data.

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Shear flocculation of celestite with sodium oleate and tallow amine acetate: effects of cations

Sodium oleate and tallow amine acetate (TAA) were used as surfactants for the shear flocculation of celestite. The shear-flocculation power values obtained with sodium oleate were higher than those obtained with TAA in terms of the concentrations used in the shear-flocculation experiments. In addition, sodium oleate and TAA were more effective on the celestite suspension in the pH ranges of 7-11 and 6-10, respectively. For the shear-flocculation experiments with sodium oleate at pH 11, with preaddition of calcium or magnesium ions at 5 x 10(-5) M and lower concentrations into the suspension, the shear flocculation of the celestite suspension was promoted by the coagulation process due to the calcium and magnesium cations added. However, the shear-flocculation power values decreased due to the interaction between surfactant and cations at concentration values higher than 5 x 10(-5) M for magnesium ions and 10(-3) M for calcium ion. Particularly, magnesium ions significantly reduced the shear-flocculation power values by slime coating of Mg(OH)2 precipitates.     

Proton transfer reactions of methylanthracene radical cations with pyridine bases under non-steady-state conditions. Real kinetic isotope effect evidence for extensive tunneling.

The kinetics of the proton transfer reactions between the 9-methyl-10-phenylanthracene radical cation (MPA(+)(.)) with 2,6-lutidine were studied in acetonitrile-Bu(4)NBF(4) (0.1 M) using derivative cyclic voltammetry. Comparisons of extent of reaction-time profiles with theoretical data for both the simple single-step proton transfer and a mechanism involving the formation of a donor-acceptor complex prior to unimolecular proton transfer were made. The experimental extent of reaction-time profiles deviated significantly from those simulated for the single-step mechanism, while excellent fits of experimental to theoretical data, in the pre-steady-state period, for the complex mechanism were observed. In this time period, the apparent deuterium kinetic isotope effects (KIE(app)) were observed to vary significantly with the extent of reaction as predicted by the complex mechanism. Resolution of the apparent rate constants into the microscopic rate constants for the complex mechanism resulted in a real kinetic isotope effect (KIE(real)) equal to 82 at 291 K. Arrhenius activation parameters (252-312 K) for the reactions of MPA(+)(*) with 2,6-lutidine in acetonitrile-Bu(4)NBF(4) (0.1 M) revealed E(a)(D) - E(a)(H) equal to 2.89 kcal/mol and A(D)/A(H) equal to 2.09. In this temperature range, KIE(real) varied from 46 at the highest temperature to 134 at the lowest. The large KIE(real), along with the Arrhenius parameters, are indicative of extensive tunneling for the proton transfer steps.     

Kinetics and deuterium isotope effects of proton transfer reactions of di (4-nitrophenyl) methane with alkoxide bases in appropriate alcohols

The second-order rate constants, activation parameters and primary deuterium isotope effects are reported for the proton-transfer reactions from di (4-nitrophenyl)-methane to sodium ethoxide, iso-propoxide and t-butoxide in appropriate alcohols. The mechanism for the reaction is discussed. , -(4-) , - . .     

The kinetic method reveals secondary deuterium isotope effects on the proton affinity and gas-phase basicity of glycine and alanine methyl esters

The kinetic method for measuring proton affinities (PA) and gas-phase basicities (GB) was applied to the methyl esters of simple amino acids. The experiments show that the GB and PA values for deuterium labeled glycine methyl ester are indeed greater than that of the corresponding unlabelled glycine methyl ester. The PA of -Ala-OCD₃ is also slightly greater than that of the unlabeled alanine methyl ester. The secondary isotope effects originate, as shown by density functional theory, in differences in zero-point energies and thermal-energy corrections between H and D-bearing molecules.     

One-electron oxidation of DNA oligomers that lack guanine: reaction and strand cleavage at remote thymines by long-distance radical cation hopping

The anthraquinone (AQ) photosensitized one-electron oxidation of DNA introduces a radical cation (electron "hole") that migrates through the duplex by hopping. The radical cation normally is trapped irreversibly by reaction at guanine. We constructed AQ-linked DNA oligomers composed exclusively of A/T base pairs. Their irradiation led to reaction and strand cleavage primarily at thymines. Long-distance radical cation hopping to distant thymines was demonstrated by the distance dependence of the process and by experiments with DNA oligomers that contain a single remote GG step. The reaction of the radical cation at thymine was shown to involve its 5-methyl group by the replacement of selected thymines with uracils. These findings show that the reactivity of radical cations in DNA cannot be explained simply by exclusive reliance on the relative oxidation potential of the nucleobases. Instead, the site of reaction is determined in accord with the Curtin-Hammett principle for reactive species in rapid equilibrium.     

Solvent and deuterium isotope effects on the lifetime of singlet oxygen determined by direct emission spectroscopy at 1.27 μm

The relative lifetime of singlet molecular oxygen have been evaluated, as a function of solvent and deuterium substitution, $\text{via}$ measurement involving the direct emission of singlet oxygen at 1.27 μm.     

Influence of the dynamic positions of cations on the structure of the DNA minor groove: sequence-dependent effects

Different models for minor groove structures predict that the conformation is essentially fixed by sequence and has an influence on local ion distribution or alternatively that temporal positions of ions around the minor groove can affect the structure if they neutralize cross-strand phosphate charges. Our previous studies show that the minor groove in an AATT dodecamer responds to local sodium ion positions and is narrow when ions neutralize cross-strand phosphate-phosphate charges [J. Am. Chem. Soc. 2000, 122, 10513-10520]. Previous results from a number of laboratories have shown that G-tracts often have a wider minor groove than A-tracts, but they do not indicate whether this is due to reduced flexibility or differences in ion interactions. We have undertaken a molecular dynamics study of a d(TATAGGCCTATA) duplex to answer this question. The results show that the G-tract has the same amplitude of minor groove fluctuations as the A-tract sequence but that it has fewer ion interactions that neutralize cross-strand phosphate charges. These results demonstrate that differences in time-average groove width between A- and G-tracts are due to differences in ion interactions at the minor groove. When ions neutralize the cross-strand phosphates, the minor groove is narrow. When there are no neutralizing ion interactions, the minor groove is wide. The population of structures with no ion interactions is larger with the GGCC than with the AATT duplex, and GGCC has a wider time-average minor groove in agreement with experiment.     

A method for the calculation of normal-mode vibrational frequencies using symmetry coordinates. Application to the calculation of secondary deuterium isotope effects on carbocations

A method is introduced for the calculation of normal-mode vibrational frequencies of polyatomic molecules based on numerical differencing of analytical gradients in symmetry coordinates. This procedure requires a number of gradient evaluations equal to the largest number of symmetry coordinates belonging to any single irreducible representation of the molecular point group (plus a single gradient evaluation at the equilibrium configuration), which is fewer than the 3N-6 (N atoms) gradient evaluations needed for schemes based on Cartesian or internal coordinates. While the proposed method will not generally be as efficient as procedures which involve the direct calculation of energy second derivatives analytically (as are now available for single-determinant wavefunctions) it appears to be equally accurate, and it should be the method of choice for frequency calculations involving multideterminant wavefunctions for which analytical second-derivative algorithms have yet to be developed. The method is illustrated by the calculation of equilibrium secondary deuterium-isotope effects on a number of reactions involving simple carbocations.     

The kinetics of isotope exchange reactions: Use of initial rates to measure isotope effects on carbon acid ionization

Multistep hydrogen isotope exchange reactions, such as the íonization of a carbon acid via a carbanion intermediate in a protic solvent, when conducted using an isotopic tracer to monitor the exchange, have the unusual feature that their rate-determining steps always refer to the transfer of the tracer isotope and never to the isotope present in macroscopic amounts. This property of these reactions is discussed and rationalized using a free energy versus reaction coordinate diagram. It is further shown that this property does not invalidate a commonly used method of measuring kinetic isotope effects on carbon acid ionization in which rates of incorporation of tritium tracers into RH and RD substrates are compared, despite the fact that tritium transfer is rate determining in both exchanges, but it is valid only if initial rate measurements are used. When the comparison is made in a protio solvent, e.g., H₂O, the portion of the initial reaction which may be used depends strongly on the magnitude of the isotope effect. It ranges from less than 1% tritium incorporation for large isotope effects to 10% or more for isotope effects near unity. On the other hand, when a deuterated solvent, e.g., D₂O, is used, the range of validity of the method for large isotope effects is extended dramatically.     

A comparison of the reactions of the oxide radical anion (o−.) with simple aromatic compounds at atmospheric and at reduced pressure conditions

The reactions of oxide radical anions (O^?.) with benzene and toluene under atmospheric pressure (APCI) and conventional chemical ionization (CI) conditions were compared. Hydrogen radical (H^?) displacement by oxygen, yielding [M ? H + O]^?, was observed in both the APCI and the CI source. However, the product, [M ? 2H]^?., derived from dihydrogen radical ion (H₂ ^+.) transfer which was observed in the CI spectra, was consistently absent under APCI conditions. This behavior is rationalized in terms of the higher pressures and chemical equilibrium associated with the APCI source. In addition to the formation of the a priori expected phenoxide isomers, the reaction of O^?. with toluene to yield the [M ? H + O]^? product generates a benzyloxide anion. Tandem mass spectrometry data from collision-induced dissociation and isotopic labeling with deuterium support a reaction mechanism initiated by α hydrogen abstraction for both the H^. and the H₂ ^+. transfer pathways.     

Stabilization and reactions of tetramethylurea radical cations in Freon matrices at 77 K: Intramolecular hydrogen transfer,ion-molecular reactions,and fragmentation by electron spin resonance study

ESR spectra for -irradiated at 77 K solutions /0.02–16%/ of tetramethylurea /TMU/ in CFCl₃ and Freon-113 have been studied. TMU^+. radical cations radiolytically produced in dilute solutions have been shown to undergo intramolecular hydrogen transfer upon photobleaching resulting in CH₂N= type radical. Evidence for intermolecular proton transfer in TMU^+. radical cations after annealing to phase transition temperature /110–120 K/ in Freon-113 was obtained. Primary radical cations of TMU^+. at their ground state take part in ion-molecular reaction via proton transfer. Molecular cations in their excited states may undergo fragmentation producing Me₂N radicals, which were trapped in liquid phase by t-BuNO as a spin trap.