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Using the pulse radiolysis and other radiation chemical techniques, the reaction kinetics of ˙CH3 and ˙CH2OH radicals with alanine anhydride, glycine anhydride and sarcosine anhydride were examined in aqueous solution. The second order rate constant of reaction of ˙CH3 with alanine anhydride has been determined at 2 × 105 dm3 mol−1 s−1. A very similar value (8 × 104 dm3 mol−1 s−1) has been obtained by measuring the methane and ethane yields as a function of the alanine anhydride concentration at different dose rates and evaluation of these data by computer analysis. Similar experiments carried out with glycine anhydride and sarcosine anhydride yielded identical rate constants of 4 × 104 dm3 mol−1 s−1 for these compounds. It was found that ˙CH2OH radical does not react with alanine anhydride at an appreciable rate (k

The reactions of methanethiyl radicals (CH3S˙) with the cyclic anhydrides of glycine (1a), alanine (L,L-1b and D,L-1b), and sarcosine (1c), and the acyclic peptides, N-formylglycinamide (3a) and N-formylalaninamide (3b), were studied by means of theoretical calculations at the B3LYP/6-311+G(d,p) level of theory. Free energies in the gas phase were determined in the classical harmonic oscillator-rigid rotator model, and used to estimate rates of H-transfer reactions at the αC-site of the peptides. The effects of aqueous solution were estimated by the SCIPCM procedure in combination with modified experimental Arrhenius A-factors to calculate solution phase rate constants. The reactions are discussed in terms of the charge and spin polarisation in the transition state, as determined by AIM analysis. Rate constants calculated by this semiempirical Arrhenius approach are in very good agreement with available experimental data on the reaction of D3N+CH2CH2S˙ with 1a and 1c but not 1b in D2O. The rate constants for the reaction of CH3S˙ with 3a and 3b are also in very good agreement with experimental data on the N-acetyl analogues. Contrary to experiment, the cyclic alanine anhydrides, L,L-1b and D,L-1b, were predicted to react more than an order of magnitude more quickly than any of the other dipeptides.

Treatment of N-alkoxy-N-chloro- or N-acetoxyamides with sodium azide in aqueous acetonitrile results in SN2 displacement of chlorine or acetate and the formation of reactive N-alkoxy-N-azidoamides which undergo a concerted decomposition to esters and nitrogen. The properties of the model N-azido-N-methoxyformamide have been computed at the B3LYP/6-31G* hybrid density functional level of theory. It is a typical anomeric amide in that the nitrogen is strongly sp3 hybridised resulting in a low amide isomerisation barrier. It decomposes in a two-step process involving exothermic loss of N2 to give 1-formyl-1-methoxydiazene which spontaneously undergoes a HERON decomposition to methyl formate and N2. Overall, the process is highly exothermic (ΔG between −654 and −659 kJ mol−1). The competitive one-step HERON process involving formation of methyl formate and tetrazene is kinetically unfavourable. Sterically hindered ester formation will be facilitated by both exothermicity and a transition state for ester formation which avoids a sterically crowded tetrahedral intermediate.

The Arrhenius parameters and rates of reaction of three hydroxyradicals, methyl radical, and the hindered primary C-centred radical from t-butyl alcohol with dithiothreitol were measured by pulse radiolysis in water. The bimolecular rate constants were found to be in the order: ˙C(CH3)2OH > ˙CH(CH3)OH > ˙CH2OH > ˙CH3 > ˙CH2C(CH3)2OH. The reaction of three of these, ˙C(CH3)2OH, ˙CH2OH, and ˙CH3, with methanethiol were examined at the ab initio B3LYP/6311+G(d,p) level, coupled with transition state theory, both in the gas phase and in solution. The solvent effects are evaluated by two different continuum models (SCIPCM, CPCM), coupled with a novel approach to the calculation of the solution phase entropy. The reaction is discussed in terms of the charge and spin polarization in the transition state, as determined by AIM analysis, and in terms of orbital interaction theory. Rate constants, calculated by transition state theory are in good agreement with the experimental data.

The 1-methyl-1-cyclohexyl cation 1 has previously been proposed to exist in superacid solution as a rapidly equilibrating pair of structures, one isomer involving C–C hyperconjugation, and a counterpart with axial C–H hyperconjugation (hyperconjomers). Using a combination of three techniques, which successfully compare theoretical results with experimental data, we have now obtained virtual proof for this concept. These three calculational procedures involve matching the experimental energy difference for the C–C and C–H hyperconjomers of 1, together with the cis-3,5-dimethyl 2 and 4,4-dimethyl 3 analogs of 1, to an accuracy of ±2 kJ mol−1 (solvation-simulation studies), a successful simulation of the α-d4 equilibrium isotope effects for the 1, 2 and 3 cation systems, and, finally, a close simulation of the average 13C NMR spectra for mixtures of these C–C and C–H hyperconjomers in the 1, 2 and 3 systems. These results have interesting implications for solvolysis studies of tertiary cyclohexyl systems, a full discussion of which is presented.

N,N′-Diacyl-N,N′-dialkoxyhydrazines are HERON amides that exhibit theoretical and physical properties of bisheteroatom-substituted amides. Amide nitrogens are pyramidal and they adopt a preferential conformation which permits an anomeric interaction in which one nitrogen overlaps strongly with the adjacent N–O σ* orbital. A crystal structure of N,N′-di(p-chlorobenzoyl)-N,N′-diethoxyhydrazine 4d has been obtained which confirms these properties in the solid state. Infrared data for ten such hydrazines indicate unusually high carbonyl stretch frequencies in accord with pyramidality at nitrogen. Diastereotopic resonances and dynamic 1H NMR studies indicate both a significant N–N rotational barrier of between 65 and 72 kJ mol–1, which is consistent with a strong anomeric interaction, as well as a much smaller than usual amide rotation barrier of 54 kJ mol–1, a direct consequence of pyramidality at nitrogen.

The [small alpha]-amino C-H bond dissociation enthalpies of glycine anhydride and alanine anhydride and the C-O bond dissociation enthalpies of the corresponding anhydride peroxyl radicals have been measured by photoacoustic calorimetry in aqueous solution. Furthermore, the one-electron oxidation potentials of the C-centered radicals formed upon hydrogen abstraction from glycine anhydride and alanine anhydride have been measured by photomodulation voltammetry in aqueous solution. In addition, the C-H bond dissociation enthalpies of glycine anhydride and alanine anhydride and one-electron reduction potentials of the corresponding radicals have been calculated by ab initio methods [at the B3LYP/6-31G(D) level]. The resulting experimental gas-phase C-H bond dissociation enthalpies are 340 and 325+/-15 kJ mol-1, the C-O bond dissociation enthalpies are 56 and 64+/-15 kJ mol-1 and the one-electron oxidation potentials are 0.175 and 0.086 V vs. NHE for the glycine anhydride and alanine anhydride related species, respectively. The calculated C-H bond dissociation enthalpies are 351.1, 334.7 and 332.7+/-10 kJ mol-1 for glycine anhydride, L-alanine anhydride and D,L-alanine anhydride, respectively. The one-electron reduction potentials of the corresponding radicals are 1.19, 1.00 and 0.99 V vs. NHE. The thermochemical properties of amino acid anhydrides and the corresponding C-centered radicals and peroxyl radicals determined in this work are consistent with each other and with previously published observations on the radical chemistry of amino acid anhydrides and related species.

The chemistry of Alzheimer's disease is largely centred on the amyloid beta-peptide, its formation, structure, and interactions with metals, membranes, proteins and other species. This critical review summarizes the current state of knowledge (252 references).

The results of a theoretical investigation (ab initio calculations) of the parent nitropyrrolidine 1 and its (R)-2-methyl and (R,R)-2,5-dimethyl derivatives 2, 3 are in good agreement with the CD, UV and 1H NMR spectra of 2, 3 and the X-ray analysis of 3. In the ground state of nitropyrrolidines l, 2 both nitrogen atoms of the nitroamino group are pyramidal and both nitrogen atoms of 3 are planar. In all cases, a small twisting of the nitroamino group about the N–N bond is observed. An envelope conformation with the C4 atom at the tip is predicted for nitropyrrolidine 1 and the more stable isomer 2a, which has a pseudoaxial methyl group. The less stable isomer 2b, (with a pseudoequatorial methyl group) and both isomers of 3 (2,5-di-pseudoaxial 3a and 2,5-di-pseudoequatorial 3b) adopt a half-chair conformation. In solutions and the crystal state, 3 exists as isomer 3a. Four Cotton effects are observed in the CD spectra of 2, 3. The signs of the Cotton effect at 270, 240 and 200 nm (the no+–π*, πN–π* and πo–π* electronic transitions) are determined by the configuration of the α-carbon chiral centres. The intrinsic chirality of the nitroamino chromophore and the chirality of the five-membered ring influence, mostly, the Cotton effect of the no––π* transition at 300 nm.

Using gas phase thermochemical data, the following Gibbs energies of formation in aqueous solution (in kJ mol–1) have been estimated for radicals of glycine: H3N+CH2CO2˙– 93, H2N˙+CH2CO2H –163, H3N+CH˙CO2H –198, H2NCH˙C(OH)2+–268, H3N+CH2CO2––371, H2NCH2CO2˙–95, H2N˙+CH2CO2––158, HN˙CH2CO2H –148, H2NCH˙CO2H –246, HN˙CH2CO2––147 and H2NCH˙CO2––208. The uncertainty in these values is estimated to be ±20 kJ mol–1.In accord with earlier EPR studies, the H2NCH˙CO2H and H2NCH˙CO2– radicals are predicted to be the most stable. Non-equivalence of the NH protons of the latter can be rationalized by a strong internal H ⋯–OCO bond. Formation of the H3N+CH2CO2˙ and H2NCH2CO2˙ acyloxyl species is expected to require very strong oxidants (E° > 3 V). Production of H2N˙+CH2CO2H and H2N˙+CH2CO2– is proposed as a better explanation of H2NCH2˙ formation in SO4˙– oxidations. The H2N˙+CH2CO2– radical, which is also susceptible to loss of CO2, would lie above H2NCH2CO2˙ in the gas phase, but its Gibbs energy of formation in aqueous solution will be ca. 0.65 V less than that of H2NCH2CO2˙. E°(H2N˙+CH2CO2–/H2NCH2CO2–) is estimated to be near 1.6 V. This is in keeping with observed one electron oxidations of H2NCH2CO2– by triplet states of organic molecules with reduction potentials in the region of 1.5–1.8 V.

The structures of HCOO˙, COOH˙, HCOO–, HCOOH˙+, HCOOH, CH2COO˙–, CH3COO˙, CH2COOH˙, CH3COO–, CH3COOH˙+ and CH3COOH were optimized at HF/6-31G(D) and MP2/6-31G(D) levels. The vibrational frequencies were calculated at the HF/6-31G(D) level and the total energies of these molecules were evaluated at the G2(MP2) level. Gas phase thermodynamic properties, Cp, S, H–H0, ΔfH and ΔfG were calculated as functions of temperature using standard statistical thermodynamic methods. For HCOO˙, COOH˙, CH3COO˙ and CH2COOH˙, the method of isodesmic reaction was used. The following are recommended values of ΔfH at 298 K in kJ mol–1: COOH˙–193, CH2COOH˙–243. CH2COO˙–322, HCOO˙–127, CH3COO˙–190, all with an uncertainty of ±7 kJ mol–1. Heats of formation of the RCOO–, and RCOOH˙+ ions were in excellent agreement with those in ref.1.On the basis of the structural information from the ab initio calculations and an analysis of the solution free energies of the parent compounds, aqueous solution free energies and free energies of formation in solution were calculated for the radicals. The values of E(RCOO˙/RCOO–) and other calculated reduction potentials for formate and acetate were shown to be in accord with rates of known redox reactions. Also the RCOO˙ radicals were predicted to have abnormally low (actually negative) pkas for the loss of C–H protons.

The long-wavelength Cotton effect (CE) of the nitroamine chromophore is very sensitive to structural non-planarity and nelicity; the sign of this CE for N-nitroaziridines has the same connection with the intrinsic chirality of the chromophore as m the case of N-acyl-, N-nitroso-aziridines and aziridinones.

The sign of the long-wavelength Cotton effect in the circular dichroism (CD) spectra of N-nitrosaziridines, possessing a non-planar nitrosamine chromophore, is determined by the intrinsic chirality of the chromophore, as in the cases of N-acylaziridines and gauche-cyclopropylketones.

Many data, collected from the literature, support the postulation of two general rules which describe the static and dynamic results of having in a molecule or generating in an intermediate adjacent electron pairs and/or polar bonds. In disagreement with current chemical intuition, structures which contain the maximum number of gauche-interactions between lone electron pairs or polar bonds represent energy minima and, frequently, the lowest minima. The stereochemical implications of the phenomenon are discussed, along with possible physical explanations. It is suggested that partitioning of the total energy of the system into attractive-dominant and repulsive-dominant interactions provides the most helpful framework for the construction of a physical picture of the phenomenon. The total energy and its components can be obtained by ab initio molecular quantum mechanical calculations.The only apparent exception to the phenomenon that has been found corresponds to a polar bond adjacent to two lone pairs (as in the case of two hetero-atoms attached to the same carbon atom). This exception, here termed the Edward–Lemieux effect, has been examined theoretically by an ab initio(Hartree–Fock) calculation using fluoromethanol as a model compound. The calculation has reproduced the Edward–Lemieux effect; the stable conformation has the C–F bond trans to one ‘electron pair’ and gauche to another, and the conformation in which the C–F bond bisects the ‘electron pairs’ is the energy maximum. The partitioning of the total energy into its components of attraction and repulsion and comparison of the results with other systems for which barriers to internal rotation have been obtained by ab initio methods reveals a similarity between fluoromethanol, hydrazine, hydroxylamine, and hydrogen peroxide. An interpretation of this result is provided in which an early suggestion by Lemieux and Chu is supported and the concept of ‘rabbit-ears’ is not.

Sulphur 3d-orbitals are not necessary to explain the structure of dimethyl sulphide dicarbanion.