Radical Stabilization Energies Research Articles

Intramolecular dimer radical cations of α,ω-di(2-naphthyl)alkanes in solutions studied by near-IR transient absorption spectroscopy

Formation of intramolecular dimer radical cations in a series of α,ω-di(2-naphthyl)alkanes (DNp n, where n is the number of carbon atoms in the methylene chain) in solutions was investigated by near-IR transient absorption spectroscopy, which enables one to quantitatively evaluate the equilibrium constant ( K) for the formation of the intramolecular dimer radical cations and stabilization energy ( E CR) due to charge delocalization. The dependence of K on n corresponds to the probability of ring closure in a syn fashion where the chain attaches at the same side of the two naphthalene (Np) moieties. The dependence of E CR on n is similar to that of K except at n=3. For DNp n with a shorter chain, the mutual configuration of the two Np moieties cannot be optimal because the ring closure itself is difficult owing to the restriction by the short chain. For DNp n with a longer chain, the two Np moieties are in a more stable configuration because of the loose restriction of the long chain. The small value of E CR at n=3 indicates that the optimal configuration for the dimer radical cation of Np is not a sandwich-like one, but a distorted one.

Performance of the RB3-LYP, RMP2, and UCCSD(T) Procedures in Calculating Radical Stabilization Energies for •NHX Radicals

N-H bond dissociation energies (BDEs) and radical stabilization energies (RSEs) associated with the •NHCF3, •NHCHO, •NHCOCH3, and •NHCONH2 radical have been calculated at a number of theoretical levels. These include UHF, RHF, UB3-LYP, RB3-LYP, UMP2, RMP2, UCCSD(T), and URCCSD(T) with a variety of basis sets, as well as the high-level composite methods W1, CBS-QB3, andG3X(MP2)-RAD. For these systems, particular care must be taken to ensure convergence to the lowest-energy solution of the self-consistent-field (SCF) equations. We have assessed the performance of the various levels of theory in calculating the BDEs and RSEs of the •NHX radicals and find that, although there are somewhat larger errors for the simpler methods, the performance generally parallels that observed previously for •CH2X radicals. In particular (and in contrast to a recent report), RB3-LYP and UCCSD(T) consistently produce very good RSEs for •NHX radicals, provided that the lowest-energy solutions are correctly identified. The RMP2 RSEs, while not as good as those for •CH2X radicals, do not show the previously claimed large errors.

Strategic use of amino acid N-substituents to limit α-carbon-centered radical formation and consequent loss of stereochemical integrity

Ab initio calculations have been used to investigate the effect of N-substituents on the stability of α-carbon-centered amino acid radicals. Optimized structures of glycine derivatives and related substituted methanes, and the corresponding 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, which were compared with the relative rates of formation of the same or closely similar radicals in reactions with N-bromosuccinimde. These studies show that N-acylation and sulfonation decrease both the stability and the ease of formation of the α-carbon-centered radicals. Greater effects are seen with fluoroacyl, fluoroalkylsulfonyl and imido groups. The extent of the effect of the imido and fluoroalkylsulfonyl groups is such that N-phthaloyl- and trifluoromethanesulfonyl-protected amino acids react by hydrogen-atom abstraction from the side chain, thereby avoiding reaction at the chiral α-center and preserving its stereochemical integrity. The origins of these substituent effects are examined.

Design of radical-resistant amino acid residues: a combined theoretical and experimental investigation.

Ab initio calculations have been used to design radical-resistant amino acid residues. Optimized structures of free and protected amino acids and their corresponding alpha-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 alpha-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 molecules. With these amino acid residues, the destabilization of the alpha-carbon-centered radicals relative to that of glycine is increased substantially to approximately 36 and 41 kJ mol(-1), respectively. The theoretical predictions have been supported by experimental observations: a tert-leucine derivative was shown to be very slow to react with N-bromosuccinimide, while the corresponding trifluoroalanine derivative was found to be inert.

Effect of carbonyls on the reactivity of polyenes in autoxidation

AbstractAutoxidation of the biologically active polyenes β‐carotene, canthaxanthin, retinyl acetate, methyl retinoate, retinal and 3,7,11,11‐tetramethyl‐10,15‐dioxo‐2,4,6,8‐hexadecatetraenal (diketoretinal) in solid amorphous films was investigated. The course of the process was followed by electronic and IR spectroscopy. The overall activation energies were obtained. It was shown that insertion in the polyene molecule of a carbonyl group conjugated with polyene chain results in a drastic decrease in the reactivity towards molecular oxygen. The results are discussed and explained on the basis of radical stabilization energy, ES(R·), as a driving force of the autoxidation process. Semi‐empirical AM1 calculations of ΔHf of some retinyl polyenes and polyenyl radicals were carried out and the C—H bond strengths and ES(R·) values of corresponding polyenyl radicals were evaluated. It was shown that the incorporation of a carbonyl group in the polyene results in a decrease in the overall autoxidation rate due to the decrease in both the initiation and propagation rates. Copyright © 2003 John Wiley & Sons, Ltd.

Quantitative Structure–Property Relationships for Aryldiazonia

By the fact of finding 43 relationships, we have shown that the reduction potentials, dimerization potentials and potentials in half-equivalent point on titration of aryldiazonium cations XC6H4N+≡N (chemical reduction with K4[Fe(CN)6] and TiCl3 in water, (C2H5)3N, (í-C4H9)4N+−OH, CH3OK and C10H8•−Na+ in acetone; polarographic reduction in nitromethane, sulfolane, and N,N-dimethylformamide) are related linearly to the quantum chemically evaluated electron affinities (A) and to the stabilization energies of radicals formed on diazonium cations reduction. Sixty six linear correlations of frequencies (ν) characterizing a collection of bonds stretching vibrations of the C-N+≡N fragment in the XC6H4N+≡NY− salts with different anions in vaseline oil, N,N-dimethylformamide, acetone, ethylacetate, methanol, water, with the bonds orders of N≡N and C-N, with the charges on carbon atoms in para positions of the C6H5X molecules aromatic rings, with the mesomeric dipole moments (μm) of X substituents have been found. Twelve quantitative relationships combining the μm and ν quantities with the A values have been established. The interrelations obtained have an explicitly expressed physical meaning, are featured by rather high correlation coefficients and have a predictive power in respect to redox properties, electron affinities, vibrational frequencies of aryldiazonia, as well as to mesomeric dipole moments of atomic groups in organic molecules.

Radical Stabilization Energies of Substituted XNH• Radicals

The performances of a number of theoretical methods in the calculation of N−H bond dissociation energies and radical stabilization energies associated with the X−NH• radicals were examined. It was found that the UHF, UMP2, and UMP4 methods were not reliable for the nitrogen radicals because of the spin contamination suffered by them. Surprisingly, the ROHF, ROMP2, and ROB3LYP methods were not found to be reliable for the nitrogen radicals either, because they could lead to unrealistic spin-localization of the radical. This unrealistic spin-localization was even seen with the UCCSD(T) method. The only credible modest-level method for the nitrogen radical was found to be UB3LYP, which could provide at least qualitatively correct radical stabilization energies for the nitrogen radicals. The basis set effect on the UB3LYP calculation was also found to be very small. Nevertheless, G3 and CBS-Q methods were found to be able to provide fairly accurate bond dissociation energies and radical stabilization energies for the substituted nitrogen radicals. According to G3 and CBS-Q results, CH3, NH2, OH, F, Cl, and CN were assigned to be stabilizing substituents for the nitrogen radical, as these groups could effectively delocalize the odd electron on the nitrogen radical. By contrast, COCH3, CONH2, COOH, and CHO were assigned to be destabilizing substituents for the nitrogen radical, although these groups could also delocalize the odd electron on the nitrogen radical. The origin of the destabilization effect was found to be the loss of the conjugation between the NH2 lone-pair electrons and the substituent from the neutral X−NH2 molecule to the X−NH• radical.

Engineering reactions in crystalline solids: predicting photochemical decarbonylation from calculated thermochemical parameters.

A detailed thermochemical analysis of the alpha-cleavage and decarbonylation reactions of acetone and several ketodiesters was carried out with the B3LYP/6-31G* density functional method. The heats of formation of several ground-state ketones and radicals were calculated at 298 K to determine bond dissociation energies (BDE) and radical stabilization energies (RSE) as a function of substituents. Results show that the radical-stabilizing abilities of the ketone substituents play a very important role on the thermodynamics of the alpha-cleavage and decarbonylation steps. An excellent correlation between calculated values and previous experimental observations suggests that photochemical alpha-cleavage and decarbonylation in crystals should be predictable from knowledge of excitation energies and the RSE of the substituent.

Radical stabilization energy as a measure of the spectral properties and reactivity trends in homologous groups

AbstractThe existence of linear relationships has been demonstrated between stretching frequencies of R—H, RO—H, CH3CON(R)—H and R—OX (X = H for alcohols and O for peroxy radicals) bonds and radical stabilization energies, Es(R·), of related radicals. The correlation equations of Es(R·) and R—H bond dissociation energies (BDE), D(R—H), with the above stretching frequencies were obtained. From the equations the D(R—H) values for different hydrocarbons were calculated and compared with the experimental data. The mean difference between calculated and experimental values for saturated hydrocarbons is 2.3 kJ mol−1. The greater differences for some unsaturated hydrocarbons are discussed and explained. The BDEs calculated from the D(R—H = f (ν) equations may be regarded as the best. The IR spectra of menthol, menadione, 3‐methylpent‐2‐en‐4‐yn‐1‐ol and retinol were recorded in solution and the Es(R·) values of the corresponding radicals and the D(R—H) values of the related C—H bonds in the parent hydrocarbons were estimated for the first time. It is also shown that the radical stabilization energy may be used to estimate the reactivity of organic compounds in free radical reactions. One may conclude that the stabilization energy of the radicals of many organic compounds could be estimated from the vibrational spectra. The Es(R·) itself is a useful quantity for predicting kinetic and spectral properties of organic compounds. Copyright © 2001 John Wiley & Sons, Ltd.

Bond Dissociation Energies and Radical Stabilization Energies Associated with Substituted Methyl Radicals

Bond dissociation energies (BDEs) and radical stabilization energies (RSEs) associated with a series of 22 monosubstituted methyl radicals (•CH2X) have been determined at a variety of levels including, CBS-RAD, G3(MP2)-RAD, RMP2, UB3-LYP and RB3-LYP. In addition, W1‘ values were obtained for a subset of 13 of the radicals. The W1‘ BDEs and RSEs are generally close to experimental values and lead to the suggestion that a small number of the experimental estimates warrant reexamination. Of the other methods, CBS-RAD and G3(MP2)-RAD produce good BDEs. A cancellation of errors leads to reasonable RSEs being produced from all the methods examined. CBS-RAD, W1‘ and G3(MP2)-RAD perform best, while UB3-LYP performs worst. The substituents (X) examined include lone-pair-donors (X = NH2, OH, OCH3, F, PH2, SH, Cl, Br and OCOCH3), π-acceptors (X = BH2, CHCH2, C⋮CH, C6H5, CHO, COOH, COOCH3, CN and NO2) and hyperconjugating groups (CH3, CH2CH3, CF3 and CF2CF3). All substituents other than CF3 and CF2CF3 result in radical stabilization, with the vinyl (CHCH2), ethynyl (C⋮CH) and phenyl (C6H5) groups predicted to give the largest stabilizations of the π-acceptor substituents examined and the NH2 group calculated to provide the greatest stabilization of the lone-pair-donor groups. The substituents investigated in this work stabilize methyl radical centers in three general ways that delocalize the odd electron: π-acceptor groups (unsaturated substituents) delocalize the unpaired electron into the π-system of the substituent, lone-pair-donor groups (heteroatomic substituents) bring about stabilization through a three-electron interaction between a lone pair on the substituent and the unpaired electron at the radical center, while alkyl groups stabilize radicals via a hyperconjugative mechanism. Polyfluoroalkyl substituents are predicted to slightly destabilize a methyl radical center by inductively withdrawing electron density from the electron-deficient radical center.

Understanding Trends in C-H, N-H, and O-H Bond Dissociation Enthalpies

Theory and experiment are now in good agreement for bond dissociation enthalpies (BDE's) and can be used as checks on each other to identify anomalous data. Both theory and experiment agree that XO-H, XNH-H, and XCH2-H BDE's decrease monotonically by ca. 60 kJ/mol along the series for X = H, but by only ca. 13 kJ/mol for X = CH3. More surprising is the fact that for X = C6H5 the O-H bond is the weakest and the N-H bond is the strongest (by 10-15 kJ/mol). By contrast, BDE's are essentially identical for X = CF3 and X = H. These interesting trends are discussed in terms of a number of concepts useful in advanced organic chemistry courses, including electronegativity, bond length, orbital overlap, unpaired electron delocalization by conjugation and hyperconjugation, and radical stabilization energy. The discussion is supported by EPR data for unpaired electron spin densities and the most recent thermochemical data for BDE's.

Molecular modelling of some para-substituted aryl methyl telluride and diaryl telluride antioxidants

Quantum mechanical calculations using the 3-21G(d) basis-set were performed on some p-substituted diaryl tellurides and aryl methyl tellurides, and the corresponding cationic radicals of these compounds. Calculated relative radical stabilization energies (RSE:s) were shown to correlate with experimentally determined peak oxidation potentials (R=0.93) and 125Te-NMR chemical shifts (R=0.91). A good correlation was also observed between the RSE:s and the Mulliken charge at the tellurium atoms (R=0.97). The results showed that Hartree–Fock calculations using the 3-21G(d) basis set was sufficiently accurate for estimating the impact of p-substituents in aryl tellurides on experimentally determined properties such as peak oxidation potentials and 125Te-NMR chemical shifts.

The EPR D parameter as a measure of spin delocalization in cyclopentane-1,3-diyl triplet diradicals with extended conjugation π-type substituents

π-Substituted cyclopentane-1,3-diyl triplet diradicals 2 were readily prepared from the corresponding azoalkanes 1 by photodenitrogenation in a 2-methyltetrahydrofuran matrix at 77 K. The D values of these triplet diradicals, obtained from the EPR spectra under matrix isolation, depend on the π substituent in the order butadienyl > 2-anthryl > vinyl > 2-naphthyl > phenyl. Good linear correlations of the D values have been obtained with the reported hyperfine coupling constants (α-hfc), with the ab initio (B3LYP) spin densities for the corresponding monoradicals 3, and with the radical stabilization energies (RSE). The present results for these extended π systems are compared with those for previously reported heteroaryl-substituted triplet diradicals.

Methylenecyclopropane Rearrangement as a Probe for Free Radical Substituent Effects. sigma (*) Values for Potent Radical-Stabilizing Nitrogen-Containing Substituents.

A series of nitrogen-containing 2-aryl-3,3-dimethylmethylenecyclopropanes have been prepared and rearrangement rates to the corresponding 2-arylisopropylidenecyclopropanes have been measured. These rates are dependent on the nature of the nitrogen-containing group in the para-position of the aryl group. Rearrangement rates have been used to calculate sigma (*) values, which are a measure of the radical stabilizing ability of the substituent. Groups such as p-N=N-Bu-t, p-CH=N-Bu-t, p-NH(2), p-CH=N-OH, and p-CH=N-OCH(3), are "good" radical stabilizers. We have also classified groups such as p-CH=N-NMe(2), p-N=N-Ph, p-N=N(O)-Bu-t, p-CH=N(O)-Bu-t, and p-CH=N-O(-) M(+), which have an extraordinarily large radical stabilizing effect, as "Super Stabilizers". These substituents stabilize the transition state of the methylenecyclopropane rearrangement by extensive spin delocalization. In the case of the latter three substituents, nitroxyl type stabilization is proposed. Density functional calculations (B3LYP/6-31G) have been carried out on a series of nitrogen-containing substituted benzylic radicals. Rates of the methylenecyclopropane rearrangement correlate with radical stabilization energies (DeltaE) determined from an isodesmic reaction of substituted benzylic radicals with toluene. These calculations confirm substantial spin delocalization onto the nitrogen-containing substituents on the para-position of the benzylic radical.

Cyanovinyl radical: an illustration of the poor performance of unrestricted perturbation theory and density functional theory procedures in calculating radical stabilization energies

Stabilization energies for the 1-cyanovinyl radical (CH2=CCN) have been calculated using a variety of conventional ab initio (Moller–Plesset, quadratic configuration interaction and coupled-cluster) and density functional theory (B-LYP, B3-LYP) procedures, as well as with a range of compound methods. Compared with a high-level benchmark value (that predicts a stabilization energy of 17.1 kJ mol−1), UMP2 and UMP4 give the wrong sign and magnitude of the stabilization energy (both methods predicting desta- bilization instead of stabilization), while B-LYP and B3-LYP overestimate the degree of stabilization. The RMP2, RMP4, QCISD(T) and CCSD(T) techniques, and several, but not all, variants of G2 and CBS theories give radical stabilization energies in good agreement with the benchmark value.

Reactivity of polyenes in solid‐state autoxidation

The reactivity of polyenes (β-carotene, canthaxanthin, lycopene and some retinyl polyenes as related compounds) in the solid state towards molecular oxygen at various temperatures and oxygen pressures was studied. The specimens were thin (ca 0.1 µm) amorphous films prepared by evaporation of one or two drops of appropriate solution on quickly rotating supports. The autoxidation was monitored by recording the changes in the electronic and infrared spectra of oxidizing films and was demonstrated to be a chain free-radical process with extremely high chain-initiation rates (10−5–10−6 mol l−1 s−1). For various polyenes the kinetic parameters of the initiation reaction were measured. In the films of several polyenes (retinyl acetate, retinal, methyl retinoate, β-carotene), the formation of free radicals proceeds in the absence of oxygen and the mechanism of the process was suggested. The observed ratios of the propagation and termination rate constants depend on the oxygen pressure, indicating the involvement of polyenyl radicals in the chain termination process. The observed trends are explained using the concepts of the stabilization energy of radicals, the reversibility of oxygen addition to polyenyls and morphological features of polyene films. Copyright © 1999 John Wiley & Sons, Ltd.

An assessment of theoretical procedures for the calculation of reliable radical stabilization energies †‡

The performance of a variety of theoretical methods in computing stabilization energies of the substituted methyl and vinyl radicals ˙CH2F, ˙CH2CN, ˙CH2CHCH2, ˙CH2CHO, CH2C˙F and CH2C˙CN is examined. The influence of electron correlation (UHF, UMP2, PMP2, RMP2, UB3-LYP, UQCISD, UQCISD(T), UCCSD(T), URCCSD(T) and RRCCSD(T)) and basis set size (from 6-31G(d) to 6-311++G(3df,3pd)) on stabilization energies is evaluated, as well as the performance of compound methods such as G2, G3, CBS-Q and CBS-APNO and their variants. The results indicate that generally reliable radical stabilization energies can be obtained at modest cost using RMP2/6-311+G(2df,p)//RMP2/6-31G(d) energies. A slightly less accurate but more economical procedure is RMP2/6-311+G(d)//B3-LYP/6-31G(d). UMP2 and PMP2 are unsuitable for obtaining radical stabilization energies for spin-contaminated radicals, while UB3-LYP appears generally to overestimate stabilization energies.

Deprotonating Molecules and Free Radicals to Form Carbon-Centered Anions: A G2 ab Initio Study of Molecular and Free Radical Acidity

Molecules CH3X and free radicals •CH2X can be deprotonated to form carbon-centered anions CH2X- and radical anions HCX•-, respectively. We have studied the geometric and thermochemical changes that accompany such deprotonation processes for a variety of substituents X including the π-donor groups NH2, OH, OCH3, PH2, SH, F, Cl, and Br and the π-acceptor groups BH2, AlH2, CHO, NO2, CN, and NC. Thermochemical properties calculated and discussed include the gas-phase acidities of the molecules and free radicals, the electron affinities of the •CH2X free radicals, various dissociation energies, and the heats of formation of all species. The acidities of •CH2X radicals are predicted to be greater than those of CH3X for π-donor substituents but less for π-acceptor substituents (except CN and NC). The changes that are predicted to occur upon deprotonation in C−X bond lengths, C−X homolytic and heterolytic bond dissociation enthalpies, C−H homolytic bond dissociation enthalpies, and radical stabilization energies may be understood by examining the orbital interactions that take place in each species.

Estimation of Bond Dissociation Energies and Radical Stabilization Energies by ESR Spectroscopy

Correlations of various indices of the stability and reactivity of carbon-centered radicals with ESR hyperfine splitting constants have been examined. For a large number of mono- and disubstituted radicals there is a moderately good linear correlation of α-proton hyperfine splitting constants (a(Hα)) with radical stabilization enthalpies (RSE) and with BDE(C−H), the C−H bond dissociation energies for the corresponding parent compounds determined from thermodynamic and kinetic studies of C−C homolysis reactions. There is a similarly satisfactory linear correlation of a(Hα) with BDE(C−H) determined by Bordwell's electrochemical and acidity function method. In all cases the correlations fail for nonplanar radicals. As expected, β-proton hyperfine splitting constants (a(HβMe)) for radicals with a freely rotating methyl substituent are less sensitive to deviations from planarity and give better linear correlations with RSE and BDE(C−H). The correlations cover a range of more than 20 kcal/mol and are reliable predictors of RSE and BDE(C−H) for a variety of radicals including captodative species. However, the correlations fail for significantly nonplanar radicals and for radicals with cyclic delocalized systems, e.g., cyclopentadienyl. The ratio a(HβMe)/a(Hα) for suitably substituted radicals provides an index of pyramidalization and allows one to decide for which compounds values of RSE and BDE(C−H) can be confidently estimated.

How Long Can You Make an Oxygen Chain?

This paper reports theoretical gas-phase structures and energetics using G2(MP2) theory for saturated oxygen chains of the general formula HOnH. Structural trends are discussed using a simple hyperconjugation model which is capable of giving a qualitative explanation for trends in bond lengths and dihedral angles. Bond dissociation energies (BDEs) are calculated for chains of increasing length, giving 49.9, 33.9, and 17.8 kcal/mol for H2O2, H2O3, and H2O4, respectively. From an analysis of the radical stabilization energy of the fragments remaining after dissociation, it is shown that a minimum value for the BDE for any hydrogen polyoxide is 6.4 kcal/mol, which occurs for the center bond in H2O6, and that longer chains will have a higher BDE. Decomposition pathways responsible for the observed instability of the polyoxides higher than hydrogen peroxide are discussed and results are given for three low-barrier dissociation paths: a solvent-assisted path, a base-catalyzed path, and a proton relay mechanism. These mechanisms are probably general and account for the instability of polyoxide chains in proton-containing solvents. Preventing proton transfer, e.g. by perfluoroalkylation, would therefore be expected to increase chain stability, in agreement with experimental observations.