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Michelle L Coote

Publications and source records attributed to Michelle L Coote.

14 recordsLinked to original sources
PubMed2006

Factors affecting the relative and absolute rates of beta-scission of alkoxythiocarbonyl radicals and alkoxycarbonyl radicals.

High-level ab initio calculations demonstrate that alkoxy-thiocarbonyl radicals (ROC*=S) undergo beta-scission significantly faster than alkoxycarbonyl radicals (ROC*=O) despite having similar exothermicities. The relatively low reactivity of the ROC*=O radicals is reduced further by electron-donating R groups and arises from the large polarization of the C*-O bonds of the reactant radicals. The results suggest that the generation of alkyl radicals from ROC*=S should be particularly efficient when the R group bears radical-stabilizing and/or electron-accepting groups, such as CN.

Journal Article↗
PubMed2006

Insights into the hydrogen-abstraction reactions of diol dehydratase: relevance to the catalytic mechanism and suicide inactivation.

High-level quantum chemistry calculations have been used to examine the hydrogen-abstraction reactions of diol dehydratase (DDH) in the context of both the catalytic mechanism and the enzyme dysfunction phenomenon termed suicide inactivation. The barriers for the catalytic hydrogen-abstraction reactions of ethane-1,2-diol and propane-1,2-diol are examined in isolation, as well as in the presence of various Brønsted acids and bases. Modest changes in the magnitudes of the initial and final abstraction barriers are seen, depending on the strength of the acid or base, and on whether these effects are considered individually or together. The most significant changes (ca. 20 kJ mol(-1)) are found for the initial abstraction barrier when the spectator OH group is partially deprotonated. Kinetic isotope effects including Eckart tunneling corrections (KIEs) have also been calculated for these model systems. We find that contributions from tunneling are of a magnitude similar to that of the contributions from semiclassical theory alone, meaning that quantum effects serve to significantly accelerate the rate of hydrogen transfer. The calculated KIEs for the partially deprotonated system are in qualitative agreement with experimentally determined values. In complementary investigations, the ability of DDH to become deactivated by certain substrate analogues is examined. In all cases, the formation of a stable radical intermediate causes the hydrogen re-abstraction step to become an extremely endothermic process. The consequent inability of 5'-deoxyadenosyl radical to be regenerated breaks the catalytic cycle, resulting in the suicide inactivation of DDH.

Acetaldehyde↗
PubMed2006

Reliable low-cost theoretical procedures for studying addition-fragmentation in RAFT polymerization.

Enthalpies for the beta-scission reactions, R'SC(*)(Z)SR --> R'SC(Z)=S + (*)R (for R, R' = CH(3), CH(2)CH(3), CH(2)CN, C(CH(3))(2)CN, CH(2)COOCH(3), CH(CH(3))COOCH(3), CH(2)OCOCH(3), CH(2)Ph, C(CH(3))(2)Ph, and CH(CH(3))Ph and Z = CH(3), H, Cl, CN, CF(3), NH(2), Ph, CH(2)Ph, OCH(3), OCH(2)CH(3), OCH(CH(3))(2), OC(CH(3))(3), and F) have been calculated using a variety of DFT, MP2, and ONIOM-based methods, as well as G3(MP2)-RAD, with a view to identifying an accurate method that can be practically applied to larger systems. None of the DFT methods examined can reproduce the quantitative, nor qualitative, values of the fragmentation enthalpy; in most cases the relative errors are over 20 kJ mol(-1) and in some cases as much as 55 kJ mol(-1). The ROMP2 methods fare much better, but fail when the leaving group radical (R(*)) is substituted with a group (such as phenyl or CN) that delocalizes the unpaired electron. However, provided the primary substituents on the leaving group radical are included in the core system, an ONIOM-based approach in which the full system is studied via ROMP2 (or SCS- or SOS-MP2) calculations with the 6-311+G(3df,2p) basis set and the core system is studied at G3(MP2)-RAD can reproduce the corresponding G3(MP2)-RAD values of the full systems within 5 kJ mol(-1) and is a practical method for use on larger systems.

Journal Article↗
PubMed2005

The effects of substrate orientation on the mechanism of a phosphotriesterase.

While the underlying chemistry of enzyme-catalyzed reactions may be almost identical, the actual turnover rates of different substrates can vary significantly. This is seen in the turnover rates for the catalyzed hydrolysis of organophosphates by the bacterial phosphotriesterase OpdA. We investigate the variation in turnover rates by examining the hydrolysis of three classes of substrates: phosphotriesters, phosphothionates, and phosphorothiolates. Theoretical calculations were used to analyze the reactivity of these substrates and the energy barriers to their hydrolysis. This information was then compared to information derived from enzyme kinetics and crystallographic studies, providing new insights into the mechanism of this enzyme. We demonstrate that the enzyme catalyzes the hydrolysis of organophosphates through steric constraint of the reactants, and that the equilibrium between productively and unproductively bound substrates makes a significant contribution to the turnover rate of highly reactive substrates. These results highlight the importance of correct orientation of reactants within the active sites of enzymes to enable efficient catalysis.

Binding Sites↗
PubMed2005

Effects of substituents on the stability of phosphoranyl radicals.

The effect of substituents on the geometries, apicophilicities, radical stabilization energies, and bond dissociation energies of (*)P(CH(3))(3)X (X = CH(3), SCH(3), OCH(3), OH, CN, CF(3), Ph) were studied via high-level ab initio molecular orbital calculations. Two alternative definitions for the radical stabilization energy (RSE) were considered: the standard RSE, in which radical stability is measured relative to H-P(CH(3))(3)X, and a new definition, the alpha-RSE, which measures stability relative to P(CH(3))(2)X. We show that these alternative definitions yield almost diametrically opposed trends; we argue that alpha-RSE provides a reasonable qualitative measure of relative radical stability, while the standard RSE qualitatively reflects the relative strength of the P-H bonds in the corresponding H-P(CH(3))(3)X phosphines. The (*)P(CH(3))(3)X radicals assume a trigonal-bipyramidal structure, with the X-group occupying an axial position, and the unpaired electron distributed between a 3p(sigma)-type orbital (that occupies the position of the "fifth ligand"), and the sigma orbitals of the axial bonds. Consistent with this picture, the radical is stabilized by resonance (along the axial bonds) with configurations such as X(-) P(*+)(CH(3))(3) and X(*) P(CH(3))(3). As a result, substituents that are strong sigma-acceptors (such as F, OH, or OCH(3)) or have weak P-X bonds (such as SCH(3)) stabilize these configurations, resulting in the largest apicophilicities and alpha-RSEs. Unsaturated pi-acceptor substituents (such as phenyl or CN) are weakly stabilizing and interact with the 3p(sigma)-type orbital via a through-space effect. As part of this work, we challenge the notion that phosphorus-centered radicals are more stable than carbon-centered radicals.

Free Radicals↗
PubMed2005

Should dithiophosphinate esters function as RAFT agents?

[graph: see text] High-level ab initio calculations indicate that *CH3 addition to the sulfur center of S=P(Z)(Z')SCH3 (Z,Z' = CH3, CN, OCH3, Ph) is considerably less exothermic than addition to the corresponding RAFT agents, S=C(Z)SCH3. This suggests that dithiophosphinate esters may have only limited use in controlling free-radical polymerization, but should make excellent radical chain carriers in organic synthesis. The results cast doubt on the notion that phosphoranyl radicals are more "intrinsically" stabilized than carbon-centered radicals.

Journal Article↗
PubMed2005

Trends in R-X bond dissociation energies (R = Me, Et, i-Pr, t-Bu; X = H, CH3, OCH3, OH, F): a surprising shortcoming of density functional theory.

The performance of a variety of high-level composite procedures, as well as lower-cost density functional theory (DFT)- and second-order perturbation theory (MP2)-based methods, for the prediction of absolute and relative R-X bond dissociation energies (BDEs) was examined for R = Me, Et, i-Pr and t-Bu, and X = H, CH(3), OCH(3), OH and F. The methods considered include the high-level G3(MP2)-RAD and G3-RAD procedures, a variety of pure and hybrid DFT methods (B-LYP, B3-LYP, B3-P86, KMLYP, B1B95, MPW1PW91, MPW1B95, BB1K, MPW1K, MPWB1K and BMK), standard restricted (open-shell) MP2 (RMP2), and two recently introduced variants of MP2, namely spin-component-scaled MP2 (SCS-MP2) and scaled-opposite-spin MP2 (SOS-MP2). The high-level composite procedures show very good agreement with experiment and are used to evaluate the performance of the lower-level DFT- and MP2-based procedures. The best DFT methods (KMLYP and particularly BMK) provide very reasonable predictions for the absolute heats of formation and R-X BDEs for the systems studied. However, all of the DFT methods overestimate the stabilizing effect on BDEs in going from R = Me to R = t-Bu, leading in some cases to incorrect qualitative behavior. In contrast, the MP2-based methods generally show larger errors (than the best DFT methods) in the absolute heats of formation and BDEs, but better behavior for the relative BDEs, although they do tend to underestimate the stabilizing effect on BDEs in going from R = Me to R = t-Bu. The potentially less computationally expensive SOS-MP2 method offers particular promise as a reliable method that might be applicable to larger systems.

Journal Article↗
PubMed2005

The kinetics of addition and fragmentation in reversible addition fragmentation chain transfer polymerization: An ab initio study.

High-level ab initio calculations of the forward and reverse rate coefficients have been performed for a series of prototypical reversible addition fragmentation chain transfer (RAFT) reactions: R* + S=C(Z)SCH3 --> R-SC*(Z)SCH3, for R = CH3, with Z = CH3, Ph, and CH2Ph; and Z = CH3, with R = (CH3), CH2COOCH3, CH2Ph, and C(CH3)2CN. The addition reactions are fast (ca. 10(6)-10(8) L mol(-1) s(-1)), typically around three orders of magnitude faster than addition to the C=C bonds of alkenes. The fragmentation rate coefficients are much more sensitive to the nature of the substituents and vary from 10(-4) to 10(7) s(-1). In both directions, the qualitative effects of substituents on the rate coefficients largely follow those on the equilibrium constants of the reactions, with fragmentation being favored by bulky and radical-stabilizing R-groups and addition being favored by bulky and radical-stabilizing Z-groups. However, there is evidence for additional polar and hydrogen-bonding interactions in the transition structures of some of the reactions. Ab initio calculations were performed at the G3(MP2)-RAD//B3-LYP/6-31G(d) level of theory, and rates were obtained via variational transition state theory in conjunction with a hindered-rotor treatment of the low-frequency torsional modes. Various simplifications to this methodology were investigated with a view to identifying reliable procedures for the study of larger polymer-related systems. It appears that reasonable results may be achievable using standard transition state theory, in conjunction with ab initio calculations at the RMP2/6-311+G(3df,2p) level, provided the results for delocalized systems are corrected to the G3(MP2)-RAD level using an ONIOM-based procedure. The harmonic oscillator (HO) model may be suitable for qualitative "order-of-magnitude" studies of the kinetics of the individual reactions, but the hindered-rotor (HR) model is advisable for quantitative studies.

Journal Article↗
PubMed2004

Consistent experimental and theoretical evidence for long-lived intermediate radicals in living free radical polymerization.

The cumyl dithiobenzoate (CDB)-mediated reversible addition fragmentation chain transfer (RAFT) polymerization of styrene at 30 degrees C is studied via both kinetic experiments and high-level ab initio molecular orbital calculations. The kinetic data clearly indicate the delayed onset of steady-state behavior. Such an observation is consistent with the slow fragmentation model for the RAFT process, but cannot be reconciled with the cross-termination model. The comprehensive failure of the cross-termination model is quantitatively demonstrated in a detailed kinetic analysis, in which the independent influences of the pre-equilibria and main equilibria and the possible chain length dependence of cross-termination are fully taken into account. In contrast, the slow fragmentation model can describe the data, provided the main equilibrium has a large fragmentation constant of at least 8.9 x 10(6) L mol(-1). Such a high equilibrium constant (for both equilibria) is consistent with high-level ab initio quantum chemical calculations (K = 7.3 x 10(6) L mol(-1)) and thus appears to be physically realistic. Given that the addition rate coefficient for macroradicals to (polymeric) RAFT agent is 4 x 10(6) L mol(-1) s(-1), this implies that the lifetime of the RAFT adduct radicals is close to 2.5 s. Since the radical is also kinetically stable to termination, it can thus function as a radical sink in its own right.

Journal Article↗
PubMed2004

Suicide inactivation of dioldehydratase by glycolaldehyde and chloroacetaldehyde: an examination of the reaction mechanism.

High-level ab initio calculations have been used to study the mechanism for the inactivation of diol dehydratase (DDH) by glycolaldehyde or 2-chloroacetaldehyde. As in the case of the catalytic substrates of DDH, e.g., ethane-1,2-diol, the 5'-deoxyadenosyl radical (Ado*) is able to abstract a hydrogen atom from both substrate analogues in the initial step on the reaction pathway, as evidenced by comparable energy barriers. However, in subsequent step(s), each substrate analogue produces the highly stable glycolaldehyde radical. The barrier for hydrogen atom reabstraction by the glycolaldehyde radical is calculated to be too high ( approximately 110 kJ mol-1) to allow Ado* to be regenerated and recombine with the cob(II)alamin radical, the latter therefore remaining tightly bound to DDH. As a consequence, the catalytic pathway is disrupted, and DDH becomes an impotent enzyme. Interconversion of equivalent structures of the glycolaldehyde radical via the symmetrical cis-ethanesemidione radical is calculated to require 38 kJ mol-1. EPR indications of a symmetrical cis-ethanesemidione structure are likely to be the result of formation of an equilibrium mixture of glycolaldehyde radical structures, this equilibration being facilitated by partial deprotonation of the glycolaldehyde radical by the carboxylate of an amino acid residue within the active site of DDH.

Acetaldehyde↗
PubMed2004

Comparison of the kinetics and thermodynamics for methyl radical addition to C=C, C=O, and C=S double bonds.

The barriers, enthalpies, and rate constants for the addition of methyl radical to the double bonds of a selection of alkene, carbonyl, and thiocarbonyl species (CH(2)=Z, CH(3)CH=Z, and (CH(3))(2)C=Z, where Z = CH(2), O, or S) and for the reverse beta-scission reactions have been investigated using high-level ab inito calculations. The results are rationalized with the aid of the curve-crossing model. The addition reactions proceed via early transition structures in all cases. The barriers for addition of methyl radical to C=C bonds are largely determined by the reaction exothermicities. Addition to the unsubstituted carbon center of C=C double bonds is favored over addition to the substituted carbon center, both kinetically (lower barriers) and thermodynamically (greater exothermicities). The barriers for addition to C=O bonds are influenced by both the reaction exothermicity and the singlet-triplet gap of the substrate. Addition to the carbon center is favored over addition to the oxygen, also both thermodynamically and kinetically. For the thiocarbonyl systems, addition to the carbon center is thermodynamically favored over addition to sulfur. However, in this case, the reaction is contrathermodynamic, addition to the sulfur center having a lower barrier due to spin density considerations. Entropic differences among corresponding addition and beta-scission reactions are relatively minor, and the differences in reaction rates are thus dominated by differences in the respective reaction barriers.

Journal Article↗
PubMed2003

Variable trends in R-X bond dissociation energies (R = Me, Et, i-Pr, t-Bu).

[structure: see text] High level ab initio molecular orbital calculations confirm experimental indications that the effect of alkyl substituents (R = Me, Et, i-Pr, t-Bu) on R-X bond dissociation energies varies considerably according to the nature of X. A simple qualitative explanation in terms of valence-bond theory is presented, highlighting the increasing importance of the stabilization of R-X by the ionic R(+)X(-) configuration for electronegative X substituents (such as F, OH, and OCH(3)).

Journal Article↗
PubMed2003

Ab initio evidence for slow fragmentation in RAFT polymerization.

High-level ab initio molecular orbital calculations on model reversible addition-fragmentation transfer (RAFT) polymerization reactions indicate that the retardation effect that is widely observed for methyl acrylate polymerization in the presence of cumyl dithiobenzoate may be attributed to the slow fragmentation of the RAFT adduct radical.

Journal Article↗