Showing papers on "Hydrogen atom abstraction published in 2003"
TL;DR: Rate constants, k(ArOH/dpph*)(S), for hydrogen atom abstraction from 13 hindered and nonhindered phenols by the diphenylpicrylhydrazyl radical, dpph*, have been determined in n-heptane and a number of alcoholic and nonalcoholic, hydrogen-bond accepting solvents.
Abstract: Rate constants, k(ArOH/dpph*)(S), for hydrogen atom abstraction from 13 hindered and nonhindered phenols by the diphenylpicrylhydrazyl radical, dpph*, have been determined in n-heptane and a number of alcoholic and nonalcoholic, hydrogen-bond accepting solvents. Abnormally enhanced k(ArOH/dpph*)(S) values of have been observed in alcohols. It is proposed that this is due to partial ionization of the phenols and a very fast electron transfer from phenoxide anion to dpph*. The popular assessment of the antioxidant activities of phenols with dpph* in alcohol solvents will generally lead to an overestimation of their activities.
404 citations
TL;DR: The computations reveal a novel mechanism whereby the active species of the enzyme catalyzes directly the production of phenol and cyclohexenone, and the potential generality of protonated porphyrin intermediates in P450 chemistry is discussed in the light of the H/D exchange.
Abstract: Benzene hydroxylation is a fundamental process in chemical catalysis. In nature, this reaction is catalyzed by the enzyme cytochrome P450 via oxygen transfer in a still debated mechanism of considerable complexity. The paper uses hybrid density functional calculations to elucidate the mechanisms by which benzene is converted to phenol, benzene oxide, and ketone, by the active species of the enzyme, the high-valent iron-oxo porphyrin species. The effects of the protein polarity and hydrogen-bonding donation to the active species are mimicked, as before (Ogliaro, F.; Cohen, S.; de Visser, S. P.; Shaik, S. J. Am. Chem. Soc. 2000, 122, 12892-12893). It is verified that the reaction does not proceed either by hydrogen abstraction or by initial electron transfer (Ortiz de Montellano, P. R. In Cytochrome P450: Structure, Mechanism and Biochemistry, 2nd ed.; Ortiz de Montellano, P. R., Ed.; Plenum Press: New York, 1995; Chapter 8, pp 245-303). In accord with the latest experimental conclusions, the theoretical calculations show that the reactivity is an interplay of electrophilic and radicalar pathways, which involve an initial attack on the pi-system of the benzene to produce sigma-complexes (Korzekwa, K. R.; Swinney, D. C.; Trager, W. T. Biochemistry 1989, 28, 9019-9027). The dominant reaction channel is electrophilic and proceeds via the cationic sigma-complex,( 2)3, that involves an internal ion pair made from a cationic benzene moiety and an anionic iron porphyrin. The minor channel proceeds by intermediacy of the radical sigma-complex, (2)2, in which the benzene moiety is radicalar and the iron-porphyrin moiety is neutral. Ring closure in these intermediates produces the benzene oxide product ((2)4), which does not rearrange to phenol ((2)7) or cyclohexenone ((2)6). While such a rearrangement can occur post-enzymatically under physiological conditions by acid catalysis, the computations reveal a novel mechanism whereby the active species of the enzyme catalyzes directly the production of phenol and cyclohexenone. This enzymatic mechanism involves proton shuttles mediated by the porphyrin ring through the N-protonated intermediate, (2)5, which relays the proton either to the oxygen atom to form phenol ((2)7) or to the ortho-carbon atom to produce cyclohexenone product ((2)6). The formation of the phenol via this proton-shuttle mechanism will be competitive with the nonenzymatic conversion of benzene oxide to phenol by external acid catalysis. With the assumption that (2)5 is not fully thermalized, this novel mechanism would account also for the observation that there is a partial skeletal retention of the original hydrogen of the activated C-H bond, due to migration of the hydrogen from the site of hydroxylation to the adjacent carbon (so-called "NIH shift" (Jerina, D. M.; Daly, J. W. Science 1974, 185, 573-582)). Thus, in general, the computationally discovered mechanism of a porphyrin proton shuttle suggests thatthere is an enzymatic pathway that converts benzene directly to a phenol and ketone, in addition to nonenzymatic production of these species by conversion of arene oxide to phenol and ketone. The potential generality of protonated porphyrin intermediates in P450 chemistry is discussed in the light of the H/D exchange observed during some olefin epoxidation reactions (Groves, J. T.; Avaria-Neisser, G. E.; Fish, K. M.; Imachi, M.; Kuczkowski, R. J. Am. Chem. Soc. 1986, 108, 3837-3838) and the general observation of heme alkylation products (Kunze, K. L.; Mangold, B. L. K.; Wheeler, C.; Beilan, H. S.; Ortiz de Montellano, P. R. J. Biol. Chem. 1983, 258, 4202-4207). The competition, similarities, and differences between benzene oxidation viz. olefin epoxidation and alkanyl C-H hydroxylation are discussed, and comparison is made with relevant experimental and computational data. The dominance of low-spin reactivity in benzene hydroxylation viz. two-state reactivity (Shaik, S.; de Visser, S. P.; Ogliaro, F.; Schwarz, H.; Schroder, D. Curr. Opin. Chem. Biol. 2002, 6, 556-567) in olefin epoxidation and alkane hydroxylation is traced to the loss of benzene resonance energy during the bond activation step.
301 citations
TL;DR: In this article, the effectiveness of piperidines as a coinitiator for photo-induced polymerization of triethyleneglycol dimethacrylate is compared with a few aliphatic amines and aromatic amines.
258 citations
248 citations
TL;DR: Kinetic studies, carried out in order to better understand the mechanism of the NHPI-catalyzed aerobic oxidation of cumene, are consistent with a simple kinetic model where the rate-determining step is the hydrogen atom abstraction from the hydroxylamine by cumylperoxyl radicals.
Abstract: Bond dissociation enthalpies (BDE) of hydroxylamines containing alkyl, aryl, vinyl, and carbonyl substituents at the nitrogen atom have been determined by using the EPR radical equilibration technique in order to study the effect of the substituents on the O-H bond strength of these compounds. It has been found that substitution of an alkyl group directly bonded to the nitrogen atom with vinyl or aryl groups has a small effect, while substitution with acyl groups induces a large increase of the O-H BDE value. Thus, dialkyl hydroxylamines have O-H bond strengths of only ca. 70 kcal/mol, while acylhydroxylamines and N-hydroxyphthalimide (NHPI), containing two acyl substituents at nitrogen, are characterized by BDE values of ca. 80 and 88 kcal/mol, respectively. Since the phthalimide N-oxyl radical (PINO) has been recently proposed as an efficient oxidation catalyst of hydrocarbons or other substrates, the large BDE value found for the parent hydroxylamine (NHPI) justifies this proposal. Kinetic studies, carried out in order to better understand the mechanism of the NHPI-catalyzed aerobic oxidation of cumene, are consistent with a simple kinetic model where the rate-determining step is the hydrogen atom abstraction from the hydroxylamine by cumylperoxyl radicals.
217 citations
TL;DR: This review states that cytochrome P450 enzymes catalyze a number of oxidations in nature including the difficult hydroxylations of unactivated positions in an alkyl group, and computational work has suggested that iron-oxo can react through multiple spin states, a low-spin ensemble that reacts by insertion of oxygen, and a high- spin ensemble that react by hydrogen atom abstraction to give a radical.
157 citations
TL;DR: The data indicate a mechanism of initial hydrogen-atom abstraction forming radicals that dimerize, disproportionate and are trapped by the oxidant, which appears to apply to the oxidations of toluene, ethylbenzene, cumene, indene, and cyclohexene.
Abstract: Anaerobic oxidations of 9,10-dihydroanthracene (DHA), xanthene, and fluorene by [(bpy)2(py)RuIVO]2+ in acetonitrile solution give mixtures of products including oxygenated and non-oxygenated compounds. The products include those formed by organic radical dimerization, such as 9,9‘-bixanthene, as well as by oxygen-atom transfer (e.g., xanthone). The kinetics of these reactions have been measured. The kinetic isotope effect for oxidation of DHA vs DHA-d4 gives kH/kD ≥ 35 ± 1. The data indicate a mechanism of initial hydrogen-atom abstraction forming radicals that dimerize, disproportionate and are trapped by the oxidant. This mechanism also appears to apply to the oxidations of toluene, ethylbenzene, cumene, indene, and cyclohexene. The rate constants for H-atom abstraction from these substrates correlate well with the strength of the C−H bond that is cleaved. Rate constants for abstraction from DHA and toluene also correlate with those for oxygen radicals and other oxidants. The rate constant for H-atom tr...
154 citations
TL;DR: The results reveal that the enzyme catalyzes the hydrogen-atom abstraction step with a remarkably low free-energy barrier, providing a satisfactory explanation for the experimental failure to trap the proposed catalytically competent high-valent heme Fe(IV) oxo (oxyferryl) species responsible for this hydroxylation chemistry.
Abstract: We elucidate the hydroxylation of camphor by cytochrome P450 with the use of density functional and mixed quantum mechanics/molecular mechanics methods. Our results reveal that the enzyme catalyzes the hydrogen-atom abstraction step with a remarkably low free-energy barrier. This result provides a satisfactory explanation for the experimental failure to trap the proposed catalytically competent high-valent heme Fe(IV) oxo (oxyferryl) species responsible for this hydroxylation chemistry. The primary and previously unappreciated contribution to stabilization of the transition state is the interaction of positively charged residues in the active-site cavity with carboxylate groups on the heme periphery. A similar stabilization found in dioxygen binding to hemerythrin, albeit with reversed polarity, suggests that this mechanism for controlling the relative energetics of redox-active intermediates and transition states in metalloproteins may be widespread in nature.
144 citations
TL;DR: In this paper, the pyrolysis of polypropylene was modeled at the mechanistic level to predict the formation of low molecular weight products, and differential equations were developed that describe the evolution of the moments of structurally distinct polymer species.
Abstract: The pyrolysis of polypropylene was modeled at the mechanistic level to predict the formation of low molecular weight products. Differential equations were developed that describe the evolution of the moments of structurally distinct polymer species. Unique polymer groups were devised that allowed the necessary polymeric features for capturing the pyrolysis chemistry to be tracked, while maintaining a manageable model size. The conversion among the species was described using typical free radical reaction types, including intermolecular hydrogen abstraction, midchain β-scission, end-chain β-scission, intramolecular hydrogen transfer, radical addition, bond fission, radical recombination, and disproportionation. The model included over 24 000 reactions and tracked 213 species (27 products tracked with molecular weights below 215 amu). The intrinsic kinetic parameters (a frequency factor and activation energy for each reaction) were obtained from data in the literature and previous modeling work in our labor...
121 citations
TL;DR: A rapid semiquantitative model is developed, which predicts sites on drugs that are susceptible to cytochrome P450 3A4-mediated hydrogen radical abstraction followed by a hydroxylation reaction, and can aid in identifying possible sites of metabolism catalyzed by other cyto chrome P450 enzymes.
Abstract: We have developed a rapid semiquantitative model for evaluating the relative susceptibilities of different sites on drug molecules to metabolism by cytochrome P450 3A4. The model is based on the energy necessary to remove a hydrogen radical from each site, plus the surface area exposure of the hydrogen atom. The energy of hydrogen radical abstraction is conventionally measured by AM1 semiempirical molecular orbital calculations. AM1 calculations show the following order of radical stabilities for the hydrogen atom abstractions: sp2 centers > heteroatom sp3 centers > carbon sp3 centers. Since AM1 calculations are too time intensive for routine work, we developed a statistical trend vector model, which is used to estimate the AM1 abstraction energy of a hydrogen atom from its local atomic environment. We carried out AM1 and trend vector calculations on 50 CYP3A4 substrates whose major sites of metabolism are known in the literature. A plot of the lowest hydrogen radical formation energy versus its sterically accessible surface area exposure for these 50 substrates shows that only those hydrogen atoms with solvent accessible surface area exposure g 8.0 A 2 are susceptible to CYP3A4-mediated metabolism. This approach forms the basis for our general model, which predicts sites on drugs that are susceptible to cytochrome P450 3A4-mediated hydrogen radical
120 citations
TL;DR: Findings indicate that quantum mechanical tunneling plays an important role in these reactions of PINO(*) with substituted toluenes, benzaldehydes, and benzyl alcohols, and the second-order rate constants were correlated by means of a Hammett analysis.
Abstract: The phthalimide N-oxyl (PINO) radical was generated by the oxidation of N-hydroxyphthalimide (NHPI) with Pb(OAc)4 in acetic acid. The molar absorptivity of PINO• is 1.36 × 103 L mol-1 cm-1 at λmax 382 nm. The PINO radical decomposes slowly with a second-order rate constant of 0.6 ± 0.1 L mol-1 s-1 at 25 °C. The reactions of PINO• with substituted toluenes, benzaldehydes, and benzyl alcohols were investigated under an argon atmosphere. The second-order rate constants were correlated by means of a Hammett analysis. The reactions with toluenes and benzyl alcohols have better correlations with σ+ (ρ = −1.3 and −0.41), and the reaction with benzaldehydes correlates better with σ (ρ = −0.91). The kinetic isotope effect was also studied and significantly large values of kH/kD were obtained: 25.0 (p-xylene), 27.1 (toluene), 27.5 (benzaldehyde), and 16.9 (benzyl alcohol) at 25 °C. From the Arrhenius plot for the reactions with p-xylene and p-xylene-d10, the difference of the activation energies, EaD − EaH, was 12...
TL;DR: In this article, the reactions of the phthalimide N-oxyl (PINO) radical with several hydrocarbons having different C−H bond dissociation energies (BDEs) were investigated in HOAc at 25 °C.
Abstract: The reactions of the phthalimide N-oxyl (PINO) radical with several hydrocarbons having different C−H bond dissociation energies (BDEs) were investigated in HOAc at 25 °C. The slope of the Evans−Polanyi plot is 0.38, which indicates that the reactions are mildly exothermic or almost thermoneutral. This finding is supported by the O−H BDE of N-hydroxyphthalimide (NHPI), 375 ± 10 kJ mol-1, obtained by means of a thermodynamic cycle. The observed kinetic isotope effects (KIEs) are related to the reaction free-energy changes, which can be explained by a Marcus-type equation. The comparison of the PINO radical reactions with analogous hydrogen atom abstraction reactions of the dibromide radical implies that HBr2• reactions are more exothermic than the PINO radical reactions. This factor is put forth to explain the different KIEs.
TL;DR: This methodology proved to be useful not only as a suitable strategy for the preparation of these bicyclic arrays but also for the selective oxidation of specific carbons of the carbohydrate skeleton, constituting a good procedure for the synthesis of protected N,O-uloses.
Abstract: The reaction of phenyl and benzyl amidophosphates and alkyl and benzyl carbamate derivatives of aminoalditols with (diacetoxyiodo)benzene or iodosylbenzene and iodine is a mild and selective procedure for the synthesis of chiral 7-oxa-2-azabicyclo[2.2.1]heptane and 8-oxa-6-azabicyclo[3.2.1]octane ring systems under neutral conditions. This reaction can be considered to be an intramolecular N-glycosidation that goes through an intramolecular 1,5-hydrogen abstraction promoted by an N-amido radical followed by oxidation of the transient C-radical intermediate to an oxycarbenium ion. This methodology proved to be useful not only as a suitable strategy for the preparation of these bicyclic arrays but also for the selective oxidation of specific carbons of the carbohydrate skeleton, constituting a good procedure for the synthesis of protected N,O-uloses.
TL;DR: It is shown that reaction of HOCl with glycosaminoglycans and model compounds yields chloramides derived from the N-acetyl function of the glycosamine rings, which may play a key role in disease progression and resolution, with the resulting fragments modulating the magnitude and quality of the immune response in inflammatory conditions.
Abstract: Myeloperoxidase released from activated phagocytes reacts with H(2)O(2) in the presence of chloride ions to give hypochlorous acid This oxidant has been implicated in the fragmentation of glycosaminoglycans, such as hyaluronan and chondroitin sulfates In this study it is shown that reaction of HOCl with glycosaminoglycans and model compounds yields chloramides derived from the N-acetyl function of the glycosamine rings The results of EPR spin trapping and product studies are consistent with the formation of amidyl radicals from these chloramides via both metal ion-dependent and -independent processes In the case of glycosaminoglycan-derived amidyl radicals, evidence has been obtained in studies with model glycosides that these radicals undergo rapid intramolecular abstraction reactions to give carbon-centered radicals at C-2 on the N-acetyl glycosamine rings (via a 1,2-hydrogen atom shift) and at C-4 on the neighboring uronic acid residues (via 1,5-hydrogen atom shifts) The C-4 carbon-centered radicals, and analogous species derived from model glycosides, undergo pH-independent beta-scission reactions that result in glycosidic bond cleavage With N-acetyl glucosamine C-1 alkyl glycosides, product formation via this mechanism is near quantitative with respect to chloramide loss Analogous reactions with the glycosaminoglycans result in selective fragmentation at disaccharide intervals, as evidenced by the formation of "ladders" on gels; this selectivity is less marked under atmospheric oxygen concentrations than under anoxic conditions, due to competing peroxyl radical reactions As the extracellular matrix plays a key role in mediating cell adhesion, growth, activation, and signaling, such HOCl-mediated glycosaminoglycan fragmentation may play a key role in disease progression and resolution, with the resulting fragments modulating the magnitude and quality of the immune response in inflammatory conditions
TL;DR: This work provides the first absolute rate constants for these reactions with model peptides and indicates that these reactions may be controlled by conformation and dynamic flexibility around the (alpha)C-H bonds.
Abstract: Thiyl radicals are important intermediates in biological oxidative stress and enzymatic reactions, for example, the ribonucleotide reductases. On the basis of the homolytic bond dissociation energies (BDEs) only, the αC−H bonds of peptides and proteins would present suitable targets for hydrogen abstraction by thiyl radicals. However, additional parameters such as polar and conformational effects may control such hydrogen-transfer processes. To evaluate the potential of thiyl radicals for hydrogen abstraction from αC−H bonds, we provide the first absolute rate constants for these reactions with model peptides. Thiyl radicals react with αC−H bonds with rate constants between 1.7 × 103 M-1 s-1 (N-acetylproline amide) and 4 × 105 M-1 s-1 (sarcosine anhydride). However, the correlation of rate constants with BDEs is poor. Rather, these reactions may be controlled by conformation and dynamic flexibility around the αC−H bonds.
TL;DR: The catalytic system formed by Mn(II and Co(II) or Cu( II) nitrates has shown to be particularly effective for the oxidation of ketones and aldehydes by molecular oxygen under mild conditions.
Abstract: The catalytic system formed by Mn(II) and Co(II) or Cu(II) nitrates has shown to be particularly effective for the oxidation of ketones and aldehydes by molecular oxygen under mild conditions. The process has a general character, but it is particularly selective for the oxidation of alkyl–aryl ketones to aromatic carboxylic acids, alkyl-cyclopropyl ketones to cyclopropane carboxylic acids and cycloalkanones to dicarboxylic acids. Mn salt plays a key role in this catalysis, which catalyses the enolisation of the carbonyl compound and initiates a free-radical redox chain with oxygen by an electron-transfer process. Co and Cu salts alone are inert, but they exalt the catalytic activity of the Mn salt, being more effective in the decomposition of the hydroperoxides. The same metal salt complexes, associated with TEMPO revealed particularly effective for the aerobic oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones under mild conditions (with air or oxygen at room temperature and atmospheric pressure); the mechanism of the catalysis is discussed. Thermochemical and kinetic investigations by EPR spectroscopy, concerning N-hydroxy compounds, have allowed to evaluate the Bond Dissociation Enthalpies (BDE) of several OH bonds and the absolute rate constants for the formation of the phthalimide-N-oxyl (PINO) radical from N-hydroxyphthalimide (NHPI) and for the hydrogen abstraction from several CH bonds by the PINO radical. The thermochemical and kinetic results have allowed us to explain the opposite catalytic behaviour of the two nitroxyl radicals, TEMPO and PINO, the former being an inhibitor of free radical processes, the latter a promoter of free-radical chain, and to develop new selective processes concerning the aerobic oxidation of alcohols, amines, amides, silanes and the substitution of heteroaromatic bases.
TL;DR: The Occam's Razor conclusion is that at least this adenosylcobalamin-dependent enzyme has not evolved to enhance quantum mechanical tunneling, at least within the present error bars.
Abstract: The literature hypothesis that "the optimization of enzyme catalysis may entail the evolutionary implementation of chemical strategies that increase the probability of quantum-mechanical tunneling" is experimentally tested herein for the first time. The system employed is the key to being able to provide this first experimental test of the "enhanced hydrogen tunneling" hypothesis, one that requires a comparison of the three criteria diagnostic of tunneling (vide infra) for the same, or nearly the same, reaction with and without the enzyme. Specifically, studied herein are the adenosylcobalamin (AdoCbl, also known as coenzyme B(12))-dependent diol dehydratase model reactions of (i). H(D)(*) atom abstraction from ethylene glycol-d(0) and ethylene glycol-d(4) solvent by 5'-deoxyadenosyl radical (Ado(*)) and (ii.) the same H(*) abstraction reactions by the 8-methoxy-5'-deoxyadenosyl radical (8-MeOAdo(*)). The Ado(*) and 8-MeOAdo(*) radicals are generated by Co-C thermolysis of their respective precursors, AdoCbl and 8-MeOAdoCbl. Deuterium kinetic isotope effects (KIEs) of the H(*)(D(*)) abstraction reactions from ethylene glycol have been measured over a temperature range of 80-120 degrees C: KIE = 12.4 +/- 1.1 at 80 degrees C for Ado(*) and KIE = 12.5 +/- 0.9 at 80 degrees C for 8-MeOAdo(*) (values ca. 2-fold that of the predicted maximum primary times secondary ground-state zero-point energy (GS-ZPE) KIE of 6.4 at 80 degrees C). From the temperature dependence of the KIEs, zero-point activation energy differences ([E(D) - E(H)]) of 3.0 +/- 0.3 kcal mol(-)(1) for Ado(*) and 2.1 +/- 0.6 kcal mol(-)(1) for 8-MeOAdo(*) have been obtained, both of which are significantly larger than the nontunneling, zero-point energy only maximum of 1.2 kcal mol(-)(1). Pre-exponential factor ratios (A(H)/A(D)) of 0.16 +/- 0.07 for Ado(*) and 0.5 +/- 0.4 for 8-MeOAdo(*) are observed, both of which are significantly less than the 0.7 minimum for nontunneling behavior. The data provide strong evidence for the expected quantum mechanical tunneling in the Ado(*) and 8-MeOAdo(*)-mediated H(*) abstraction reactions from ethylene glycol. More importantly, a comparison of these enzyme-free tunneling data to the same KIE, (E(D) - E(H)) and A(H)/A(D) data for a closely related, Ado(*)-mediated H(*) abstraction reaction from a primary CH(3)- group in AdoCbl-dependent methylmalonyl-CoA mutase shows the enzymic and enzyme-free data sets are identical within experimental error. The Occam's Razor conclusion is that at least this adenosylcobalamin-dependent enzyme has not evolved to enhance quantum mechanical tunneling, at least within the present error bars. Instead, this B(12)-dependent enzyme simply exploits the identical level of quantum mechanical tunneling that is available in the enzyme-free, solution-based H(*) abstraction reaction. The results also require a similar, if not identical, barrier width and height within experimental error for the H(*) abstraction both within, and outside of, the enzyme.
TL;DR: Various silylated 1,4-cyclohexadienes are presented as superior tin hydride substitutes for the conduction of various radical chain reductions and the effects of the cyclohexadiene substituents on the reaction outcomes are discussed.
Abstract: Various silylated 1,4-cyclohexadienes are presented as superior tin hydride substitutes for the conduction of various radical chain reductions. Debrominations, deiodinations, and deselenations can be performed using these environmentally benign reagents. Furthermore, Barton-McCombie-type deoxygenations using silylated cyclohexadienes are described. Radical cyclizations, ring expansions, and Giese-type addition reactions with the new tin hydride substitutes are presented. The polymerization of styrene can be regulated using silylated cyclohexadienes. Rate constants for hydrogen atom abstraction from two 1-silyl-cyclohexadienes by primary C-radicals were determined. The effects of the cyclohexadiene substituents on the reaction outcomes are discussed. Finally, qualitative EPR experiments on silyl radical expulsion from silylated cyclohexadienyl radicals are presented.
TL;DR: To design amino acid residues that would resist radical reactions, strategies by which the steric effects could be magnified were considered and resulted in the identification of tert-leucine and 3,3,3-trifluoroalanine as suitable molecules.
Abstract: Ab initio calculations have been used to design radical-resistant amino acid residues. Optimized structures of free and protected amino acids and their corresponding α-carbon-centered radicals were determined with B3-LYP/6-31G(d). Single-point RMP2/6-31G(d) calculations on these structures were then used to obtain radical stabilization energies, to examine the effect of steric repulsion between the side chains and amide carbonyl groups on the stability of α-carbon-centered peptide radicals. Relative to glycine, the destabilization for alanine and valine residues was found to be approximately 9 and 18 kJ mol-1, respectively, which correlates with the reactivity of analogous amino acid residues in peptides toward hydrogen atom abstraction in conventional free radical reactions. To design amino acid residues that would resist radical reactions, strategies by which the steric effects could be magnified were considered. This resulted in the identification of tert-leucine and 3,3,3-trifluoroalanine as suitable ...
TL;DR: The process proceeds at a much lower temperature than is required for efficient reaction with toxic tributyltin hydride in benzene and permits significantly higher isolated yields than the corresponding reaction mediated by ethylpiperidine hypophosphite (EPHP).
TL;DR: The 1-hydroxy-1-(N-methyl)aminoethyl radical (1) represents a simple model system for hydrogen atom adducts to the amide bond in gas-phase peptide and protein ions relevant to electron capture dissociation (ECD).
Abstract: The 1-hydroxy-1-(N-methyl)aminoethyl radical (1) represents a simple model system for hydrogen atom adducts to the amide bond in gas-phase peptide and protein ions relevant to electron capture dissociation (ECD). Radical 1 was generated in the rarefied gas phase by femtosecond electron transfer to the stable cation prepared by selective O-protonation of N-methylacetamide. The main dissociations of 1 were loss of the hydroxyl hydrogen atom and the N-methyl group in a 1.7:1 ratio, as deduced from product analysis and deuterium labeling. The dissociations that occur on the 4.1 microsecond time scale are driven by large Franck−Condon effects on collisional electron transfer that deposit 93−103 kJ mol-1 in the nascent radicals. Detailed analysis of the potential energy surface for dissociations of 1 revealed several conformers and isomeric transition states for dissociations of the O−H and N−CH3 bonds. The experimental branching ratio is in quantitative agreement with RRKM calculations within the accuracy of t...
TL;DR: In this article, the formation of spin-trapping spin adducts was observed in the photocatalytic experiments using deuterated methanol, where the production of C6H5N OD was established.
Abstract: The radical intermediates produced upon UV irradiation of deoxygenated alcoholic titanium dioxide suspensions of nitrosobenzene, nitrobenzene, 2-nitrosotoluene, 2,3,5,6-tetramethylnitrosobenzene, 3,5-di-bromo-4-nitrosobenzenesulfonate (sodium salt), 2,4,6-tri-t-butyl-nitroso-benzene, and 2-methyl-2-nitrosopropane were investigated using in situ EPR technique. Nitrosobenzene is efficiently photoreduced in TiO2 suspensions (toluene/alcohol, 1:1 (v/v)) forming exclusively one stable radical intermediate corresponding to C6H5N OH species. The formation of this radical species is consistent with the proposed photocatalytic reduction mechanism, occurring from the primary generated nitrosobenzene mono-anion by the hydrogen abstraction from surroundings. The origin of hydrogen added to the nitroso group was demonstrated by the photocatalytic experiments using deuterated methanol, where the production of C6H5N OD was established. Additionally, an identical radical C6H5N OH was detected, when nitrobenzene was reduced under analogous experimental conditions. The photoinduced electron transfer from TiO2 to nitroso compounds is accompanied by alcohol oxidation via the photogenerated titanium dioxide valance band holes forming alkoxy and hydroxyalkyl radicals. Production of hydroxyalkyl radicals ( CH2OH, CH(OH)CH3, C(OH)(CH3)2) with redox potentials suitable for a direct electron transfer to nitroso compounds represents an alternative reaction pathway for their reduction. On the other hand, the investigated nitroso derivatives are efficient spin-trapping agents, therefore, formation of nitroxyl radical spin adducts was observed in the photocatalytic experiments. The EPR spectra monitored upon irradiation of substituted nitrosobenzene derivatives in alcoholic TiO2 suspensions reveal the correlation between nitrosobenzene derivative first step reduction potentials and yield of radical species produced.
TL;DR: In this article, a set of 12 Benson groups transferable among these six molecular families is derived from CBS-Q results via regression together with 20 hydrogen bond increment (HBI) group values for estimating the thermochemistry of oxymethyl (˙CH2OX), oxyethyl (CH3CH˙OX), and oxyisopropyl ((CH3)2C˙ox) with varying substituent X (= H, CH3, C(O)H, C (O)E, C, CH 3, CHE, CH E, CH
Abstract: Ab initio molecular orbital theory calculations are performed at the complete basis set (CBS-Q) level to determine thermochemical parameters (ΔfH298, S298, CTp) of alcohols, methyl ethers, formates, acetates, hydroperoxides, methyl alkylperoxides and the corresponding methoxy, primary and secondary alkoxy radicals derived from these molecular families. A consistent set of 12 Benson groups transferable among these six molecular families is derived from CBS-Q results via regression together with 20 hydrogen bond increment (HBI) group values for estimating the thermochemistry of oxymethyl (˙CH2OX), oxyethyl (CH3CH˙OX), oxyisopropyl ((CH3)2C˙OX) with varying substituent X (= H, CH3, C(O)H, C(O)CH3, OH, OCH3) and alkoxycarbonyl (ROC(O)˙) radicals. These new groups are useful in estimating the thermochemistry of large oxygenated molecules and radicals involved in complex chemical reaction mechanisms. The kinetics of nearly 50 elementary bimolecular hydrogen abstraction reactions belonging to eight different reaction families viz., (i) CH3OX + H˙ → ˙CH2OX + H2, (ii) CH3OX + ˙CH3 → ˙CH2OX + CH4, (iii) CH3CH2OX + H˙ → CH3C˙HOX + H2, (iv) CH3CH2OX + ˙CH3 → CH3C˙HOX + CH4, (v)
(CH3)2CHOX + H˙ → (CH3)2C˙OX + H2, (vi) HC(O)OR + H˙ → ˙C(O)OR + H2, (vii) HC(O)OR + ˙CH3 → ˙C(O)OR + CH4, (viii) ROOH + H˙ → ROO˙ + H2 are studied using transition state theory coupled with CBS-Q energetics. The calculated barrier height within a given reaction family varies with the nature of the β substituents. The reliability of the calculated variations in the barrier height with varying β substituents is determined through comparison of the calculated rate constants with the scarcely available experimental data. Thermodynamically consistent generic rate rules have been derived in terms of group additivity. New transferable supergroup values corresponding to the thermochemistry of the reactive moiety in transition structures are developed. The effect of non-next neighbor substituents on the enthalpy of the supergroup is quantified using Evans–Polanyi relations.
TL;DR: It is shown that radical additions to C3 of an indole are frequently facile, and cyclisations involving the addition of indolyl radical intermediates to arenes have been demonstrated.
TL;DR: It is suggested that a previously overlooked reaction, namely the direct reduction of preformed lipid hydroperoxides to alkoxyl radicals by Cu(II), may be responsible for the initiation of lipid peroxidation byCu(II) ions.
Abstract: Lipid peroxidation is often initiated using CuII ions. It is widely assumed that CuII oxidizes preformed lipid hydroperoxides to peroxyl radicals, which propagate oxidation of the parent fatty acid via hydrogen atom abstraction. However, the oxidation of alkyl hydroperoxides by CuII is thermodynamically unfavorable. An alternative means by which CuII ions could initiate lipid peroxidation is by their one-electron reduction of lipid hydroperoxides to alkoxyl radicals, which would be accompanied by the generation of CuIII. We have investigated by EPR spectroscopy, in conjunction with the spin trap 5,5-dimethyl-1-pyrroline N-oxide, the reactions of various CuII chelates with tert-butylhydroperoxide. Spectra contained signals from the tert-butoxyl, methyl, and methoxyl radical adducts. In many previous studies, the signal from the methoxyl adduct has been assigned incorrectly to the tert-butylperoxyl adduct, which is now known to be unstable, releasing the tert-butoxyl radical upon decomposition. This either ...
TL;DR: In this article, an application of the reaction class transition state theory (RC-TST) in predicting thermal rate constants of the hydrogen abstraction reactions H + H−C(sp3) where C(sp 3) is a saturated carbon atom is presented.
Abstract: We present an application of the reaction class transition state theory (RC-TST) in predicting thermal rate constants of the hydrogen abstraction reactions H + H−C(sp3) where C(sp3) is a saturated carbon atom. Combining the RC-TST with the linear energy relationship (LER) allows rate constants of any reaction in the class to be estimated from only reaction energy information. We have derived from first-principles all parameters for the RC-TST/LER method so rate constants for any reaction in this class can be predicted from only reaction energy, that can easily be computed from either the density functional theory or semiempirical molecular orbital theory. We have performed error analyses for a large number of reactions in the above class for which some experimental measurements or estimates are available. By comparisons with results from full TST/Eckart calculations we also found the RC-TST/LER method is quite cost-effective and has accuracy comparable to first-principles predictions using more rigorous m...
TL;DR: The ruthenium analogue of the active species of the enzyme cytochrome P450, which is known to be among the most potent catalysts for C-H activation, is reasoned to have larger turnover numbers compared with the iron-oxo analogue, due to lesser production of suicidal side products that destroy the catalyst.
Abstract: High-valent metal-oxo complexes catalyze C-H bond activation by oxygen insertion, with an efficiency that depends on the identity of the transition metal and its oxidation state. Our study uses density functional calculations and theoretical analysis to derive fundamental factors of catalytic activity, by comparison of a ruthenium-oxo catalyst with its iron-oxo analogue toward methane hydroxylation. The study focuses on the ruthenium analogue of the active species of the enzyme cytochrome P450, which is known to be among the most potent catalysts for C-H activation. The computed reaction pathways reveal one high-spin (HS) and two low-spin (LS) mechanisms, all nascent from the low-lying states of the ruthenium-oxo catalyst (Ogliaro, F.; de Visser, S. P.; Groves, J. T.; Shaik, S. Angew. Chem. Int. Ed. 2001, 40, 2874-2878). These mechanisms involve a bond activation phase, in which the transition states (TS's) appear as hydrogen abstraction species, followed by a C-O bond making phase, through a rebound of the methyl radical on the metal-hydroxo complex. However, while the HS mechanism has a significant rebound barrier, and hence a long lifetime of the radical intermediate, by contrast, the LS ones are effectively concerted with small barriers to rebound, if at all. Unlike the iron catalyst, the hydroxylation reaction for the ruthenium analogue is expected to follow largely a single-state reactivity on the LS surface, due to a very large rebound barrier of the HS process and to the more efficient spin crossover expected for ruthenium. As such, ruthenium-oxo catalysts (Groves, J. T.; Shalyaev, K.; Lee, J. In The Porphyrin Handbook; Biochemistry and Binding: Activation of Small Molecules, Vol. 4; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000; pp 17-40) are expected to lead to more stereoselective hydroxylations compared with the corresponding iron-oxo reactions. It is reasoned that the ruthenium-oxo catalyst should have larger turnover numbers compared with the iron-oxo analogue, due to lesser production of suicidal side products that destroy the catalyst (Ortiz de Montellano, P. R.; Beilan, H. S.; Kunze, K. L.; Mico, B. A. J. Biol. Chem. 1981, 256, 4395-4399). The computations reveal also that the ruthenium complex is more electrophilic than its iron analogue, having lower hydrogen abstraction barriers. These reactivity features of the ruthenium-oxo system are analyzed and shown to originate from a key fundamental factor, namely, the strong 4d(Ru)-2p(O,N) overlaps, which produce high-lying pi(Ru-O), sigma(Ru-O), and sigma(Ru-N) orbitals and thereby to lead to a preference of ruthenium for higher-valent oxidation states with higher electrophilicity, for the effectively concerted LS hydroxylation mechanism, and for less suicidal complexes. As such, the ruthenium-oxo species is predicted to be a more robust catalyst than its iron-oxo analogue.
TL;DR: In this paper, the authors present results from computational studies by molecular orbital and density functional theories on several series of hydrogen-bonded complexes, which aim at quantifying the reactivity of molecules for the complexation process.
Abstract: The paper reviews results from computational studies by molecular orbital and density functional theories on several series of hydrogen bonded complexes. These studies aim at quantifying the reactivity of molecules for the complexation process. Excellent linear relationships are found between the electrostatic potential values at the sites of the electron donor and electron accepting atoms and the energy of hydrogen bond formation (ΔE). The series studied are: (a) complexes of R–CHO and R–CN molecules with hydrogen fluoride; (b) complexes of mono-substituted acetylene derivatives with ammonia; (c) (HCN)n hydrogen bonded cluster for n=2–7. All 22 studied complexes of carbonyl and nitrile compounds with hydrogen fluoride fall in the same dependence between the energy of hydrogen bond formation and the electrostatic potential at the atomic site of the carbonyl oxygen and nitrile nitrogen atoms, with linear regression correlation coefficient r=0.979. In the case of complexes of mono-substituted acetylene and diacetylene derivatives with NH3, the correlation coefficient for the dependence between the electrostatic potential at the acidic hydrogen atom and ΔE equals 0.996. For the series of hydrogen bonded (HCN)n clusters, the correlation coefficient for the relationship between the electrostatic potential at the end nitrogen atom and ΔE is r=0.9996. Similarly, the analogous relationship with the electrostatic potential at the end hydrogen atom has a regression coefficient equal to 0.9994. The dependencies found are theoretically substantiated by applying the Morokuma energy decomposition scheme. The results show that the molecular electrostatic potential at atomic sites can be successfully used to predict the ability of molecules to form hydrogen bonds.
TL;DR: In this article, the nascent vibrational distributions of the water molecules produced by such reactions have been obtained by analysis of the infrared chemiluminescence from H 2 O, HOD and D 2 O. The analysis required computer simulation of the spectra obtained by recording emission from a fast-flow reactor at 298 K with a low-resolution Fourier transform spectrometer.
Abstract: The formation of water molecules via hydrogen atom abstraction by hydroxyl radicals and their formation via unimolecular elimination from vibrationally excited alcohols and organic acids are important processes in a variety of gas-phase chemical environments. The nascent vibrational distributions of the water molecules produced by such reactions have been obtained by analysis of the infrared chemiluminescence from H 2 O, HOD and D 2 O. The analysis required computer simulation of the spectra obtained by recording emission from a fast-flow reactor at 298 K with a low-resolution Fourier transform spectrometer. By combining the information deduced from simulation of the H 2 O and HOD emission spectra from the reactions of OH and OD, the total vibrational energy released to the water molecule and the distribution between the stretch and bending modes have been assigned. The present report provides a summary of results from hydroxyl radicals reacting with inorganic hydride molecules, with the primary, secondar...
TL;DR: In this paper, the rate constants for hydrogen abstraction from phenols by a prefluorescent-TEMPO probe are reported, and it is shown that the mechanism is dominated by hydrogen transfer.