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The region encompassing residues 13–23 of the amyloid beta peptide (Aβ(13–23)) of Alzheimer’s disease is the self-recognition site that initiates toxic oligomerization and fibrillization. A number of pseudopeptides have been designed to bind to Aβ(13–23) and been computationally shown to do so with high affinity. More interactions are available in full-length Aβ than are available in the shorter peptide. We describe herein a study by molecular dynamics (MD) of nine distinct complexes formed by one such pseudopeptide, SGA1, with full-length beta amyloid, Aβ(1–42). The relative stabilities of the Aβ–SGA1 complexes were estimated by a combination of MD and ab initio methods. The most stable complex, designated AB1, was found to be one in which SGA1 is bound to the self-recognition site of Aβ(1–42) in an antiparallel β-sheet fashion. Another complex, designated AB3, also involved SGA1 binding to the self-recognition region of Aβ(1–42), albeit with lower affinity. In both AB1 and AB3, SGA1 formed antiparallel β-sheets but to opposite edges of Aβ. A complex, AB4, with similar stability to AB3, was found with a parallel β-sheet in the self-recognition site. A fourth complex, AB7, also with similar stability, formed a parallel β-sheet in the hydrophobic central region of Aβ. In all cases, complexation of SGA1 induced extensive β-sheet structure in Aβ(1–42).

The region encompassing residues 13–23 of the amyloid beta peptide (Aβ(13–23)) of Alzheimer’s disease is the self-recognition site that initiates toxic oligomerization and fibrillization and also is the site of interaction of Aβ with many other proteins. We describe herein a study by molecular dynamics of the complexes formed by R (= N-AcAβ(13–23)NH2(N-CH3C(O)HHQKLVFFAEDNH2)) with several pseudopeptides designed to form β-sheets with Aβ(1-40,42) and prevent oligomer and fibril formation. Adhesion to both edges of the R β-strand is examined by structure analysis. Umbrella sampling along a dissociation pathway reveals approximate free energies of binding in the submicromolar range. One of the three pseudopeptides binds strongly to one edge of the R β-strand and another to the opposite edge, while the third displays strong binding to both edges. It is desirable to block both edges of the self-recognition site of Aβ to prevent oligomer formation. The study reveals that this may be accomplished by a single pseudopeptide or two in combination. Thus the pseudopeptides, used singly or in pairs, may be competitive inhibitors of Aβ oligomerization at stoichiometric concentrations.

The region encompassed by residues 13–23 of the amyloid beta peptide (Aβ(13–23)) of Alzheimer’s disease is the self-recognition site that initiates toxic oligomerization and fibrillization and also is the site of interaction of Aβ with many other proteins. We describe herein a study by molecular dynamics of N-AcAβ(13–23)NH2 (N-CH3C(O)HHQKLVFFAEDNH2) as a model of full-length Aβ(1–40) or Aβ(1–42) and of its dimers. The effect of pH at or below physiological (pH 7.4) is assessed by protonation of one or more of the His residues. The major conformation of the monomer of the systems is a flexible folded structure. Protonation of one or both His residues does not change the conformation in any significant way. The dimers of protonated and unprotonated systems exist almost exclusively as stable antiparallel β-sheets anchored at both ends by intermolecular salt bridges between Lys16 of one chain and the C-terminal residues Glu22 and Asp23 of the other. We also employ the technique of “umbrella sampling” whereby relative binding affinities of the complexes could be determined. In the case of unsymmetrically protonated species, each complex begins dissociation by releasing the weaker salt bridge, breaking interstrand hydrogen bonds, and losing the β-sheet character. The stronger salt bridge is the last to release and presumably is the first to form in the reverse process of aggregation. Umbrella sampling yields the free energy profiles of the dissociation as a function of the separation of the centres of mass. For each system, the dissociation profile has only a shallow maximum. By implication, the reverse process of assembly has almost no barrier. This is an example of entropy–enthalpy compensation that arises naturally during the molecular dynamics – umbrella sampling simulation.

This paper investigates the origin of the anomalous anomeric effect in merosinigrin, a 2-cyanothiane in which the cyano group is axial as expected for the anomeric effect, but in which bond distances are opposite to that expected from the nS→[Formula: see text] orbital interaction, which underlies the classical anomeric effect. The model compounds, 2-cyanooxane, 2-cyanothiane, and 2-cyanoselenane, were synthesized and studied both experimentally and computationally. Both the thia and selena systems displayed an even higher preference for the axial conformation than the oxa system but also exhibited the bond length anomalies found previously in merosinigren. Natural bond order (NBO) analysis of the B3LYP/6–311+G(3df,2p) wave functions of the axial and equatorial forms of the three systems confirmed a weakening of the n→σ* orbital interaction in the O, S, and Se series, and a strengthening of a σ–π*(CN) interaction that explains the bond length reversals observed in the S and Se systems. It also revealed a new mechanism, n→π*, namely, a through-space interaction between the nonbonded lone pair electrons of the heteroatom and the π* orbital of the cyano group, which selects for the axial conformation.

The structures and relative free energies in aqueous solution of the Cu(II) complexes of the “histidine walk” peptides, AcHGGGNH2, AcGHGGNH2, AcGGHGNH2, and AcGGGHNH2, were determined as a function of pH. Numerous structures of each species were found by gaseous- and solution-phase geometry optimization at the B3LYP/6–31G(d) level, and the effect of solvation estimated by the IEFPCM continuum solvation model. Free energies of solvation of the ionic species are large and favour structures with an extended peptide chain. In all Cu(II)–peptide complexes, deprotonation of two amide groups occurs readily at or below pH 7. In each system, the most abundant species at pH 7 is a neutral 1:1 complex with N3O1 coordination pattern. Binding in the forward direction toward the C terminus is preferred. The results are compared to recent experimental spectroscopic and potentiometric studies on related systems. Alternative explanations are offered for some of the experimental observations.

The possibility of sulfur–nitrogen (S—N) three-electron bond formation in a one-electron oxidized methionine peptide model was investigated computationally following the detection of such species in pulse radiolysis experiments (C. Schöneich, D. Pogocki, G.L. Hug, and K. Bobrowski. J. Am. Chem. Soc. 125, 13700 (2003)). Geometry optimiza tions were carried out at the B3LYP/6-31G(d) level of theory. Relative free energies in aqueous solution at pH 7 were predicted for all intermediates with enthalpy evaluations at the CCSD(T)/6-31+G(d′) level and free energies of solvation predicted using a continuum model (CPCM). Both the initial oxidation product and the intermediate formed at higher pH were identified as cyclic S—N bonded species in which the intramolecular three-electron interaction is between the S atom and the π orbital of the amide group. TD-B3LYP calculations of the UV spectra support the assignments. A mechanism for the conversion to the most stable α-C-centered radical is proposed. The mechanism involves a novel deprotonation–reprotonation via an intermediate backbone-delocalized radical anion.Key words: methionine oxidation, three-electron bonding, S—N bonding, B3LYP.

The origin of the HERON reaction is reviewed from a historical perspective and shown to have its foundation in the unusual properties of bisheteroatom-substituted amides, so-called anomeric amides. The reaction involves migration of anomerically destabilized oxo-substituents on an amide nitrogen to the amide carbon and dissociation of the amide bond. Computational work providing a theoretical basis for the reaction is presented, together with physical organic measurements that support results therefrom. The rearrangement has been observed in a number of chemical transformations of N-alkoxy-N-aminoamides, reactions of 1-acyloxy-1-alkoxydiazenes, N-alkoxy-N-aminocarbamates, N-alkoxyhydroxamic acids, as well as in the gas-phase reactions of N-acyloxy-N-alkoxyamides.Key words: HERON reaction, anomeric amides, rearrangements, hindered esters, concerted reactions.

The structures and reactivities of the alkoxy radicals methoxy (CH3O·), ethoxy (CH3CH2O·), 1-propoxy (CH3CH2CH2O·), 2-propoxy ((CH3)2CHO·), 2-butoxy (CH3CH2CH(CH3)O·), tert-butoxy ((CH3)3CO·), prop-2-enoxy (CH2=CHCH2O·), and but-3-en-2-oxy (CH2=CHCH(CH3)O·) have been investigated at the B3-LYP/6-31G(d) and CBS-RAD levels of theory. Enthalpies of formation (ΔfH°298) were calculated with CBS-RAD for all the alkoxy radicals, the carbonyl and radical products of β-scission reactions, and the transition structures leading to them. The mean absolute deviation between the predicted and available experimental ΔfH°298 values is 5.4 kJ mol–1. Eyring (ΔH‡0, ΔH‡298, ΔG‡298) and Arrhenius (log A, Ea) activation parameters for both the forward (β-scission) and reverse (radical addition to carbonyl) pathways were calculated. Agreement with available experimental data is very good, generally within 1–5 kJ mol–1 for Ea, and 0.5 for log A. The transition structures are found to be substantially polarized, with the departing radical slightly positive, the O atom negative, and the rest of the molecule positive. The barriers for the β-scission reactions decrease with decreasing endothermicity and with decreasing ionization energy of the departing radical.Key words: alkoxy, alkoxyl, radical, addition, carbonyl, β-scission, calculaton, electronic structure, B3LYP, CBS-RAD, thermochemistry.

Pathways for oxidation of the parent nitrosoamine 2, nitrosodimethylamine 3, and anti- nitrosoethylmethylamine 4 by the parent dioxirane 1 have been explored computationally using the B3LYP hybrid density functional theoretical method in conjunction with the 6-31G* and 6-311+G** basis sets. Oxygen transfer from 1 to the nitrogen of the NO group (NO oxidation), yielding nitroamines 5,7, and 10, has the lowest activation barrier (15, 12.8, and 12 kcal mol-1 for 2, 3, and anti-4, respectively). Oxidation of the amine nitrogen (N oxidation) in 2, 3 leads to nitric oxide and nitroxyl radicals 6, 8 and is characterized by the highest activation energy: 28.5 kcal mol-1 for 2, 22.3 kcal mol-1 for 3. The potential barrier to hydroxylation of the methyl groups in 3 (CH oxidation) is intermediate - ca. 19 kcal mol-1. Introduction of a methyl group to the carbon reaction centre decreases the activation barrier of the anti-CH oxidation by 2-3 kcal mol-1. In 3, a gas-phase small preference for anti-CH oxidation over syn-CH oxidation, 0.1 kcal mol-1, is predicted to increase dramatically to 4.7 kcal mol-1 when the reaction is carried out in a dielectric medium (acetone, IPCM model). In general, polar solvents (CH2Cl2, acetone) lower the activation barriers for the NO, N, and CH oxidations, more so for the species of higher polarity than those of lower polarity (reactive complexes (1+3), (1+anti-4), transition state anti,syn-TSCH(1+4)]. However, the chemoselectivity (EaNO aanti-CH asyn-CH aN) in the polar solvents is predicted to be the same as in the gas phase.Key words: dioxirane, nitrosoamines, oxidation, ab initio, omputation.

After hydrogenation and hydrolysis, the two adducts formed from the Diels-Alder reaction of acryloyl chloride and 4,5,6,6a-tetrahydropentalene were originally assigned 7-exo- and 7-endo-carboxylic acid structures 3 and 4. Based on unexpected results in using these acids as starting materials for a superacid carbocation study, a reinvestigation of these structural assignments was carried out. From an extensive series of 2D NMR experiments, we conclude that 4 is correctly assigned, but that the other isomer is the 9-endo carboxylic acid 8. The formation of these two isomers (out of eight possible modes of addition) can be rationalized. Finally, an X-ray study of 8 was carried out as a final proof of structure.Key words: Diels-Alder reaction, facial selectivity, regioselectivity, X-ray structure, MO calculation.

Ab initio computations (B3LYP/6-31G(D), coupled with isodesmic reactions) were used to predict αC→H bond dissociation energies (BDEs) for proline as a residue in a model peptide, intended to mimic the environment in proteins. The environment was further constrained to mimic common proline positions in turns of different types. The BDEs were found to be very dependent on the structural constraints imposed by the turn type, implying different structure-mediated susceptibilities to free radical damage to proline residues. Unnatural repair of proline (inversion of chirality) was found to be thermodynamically unfavourable. The predicted BDEs for the proline αC→H bond, in kJ mol-1, to an estimated accuracy of ±10 kJ mol-1 are as follows: fully optimized trans rotamer, 368.6; fully optimized cis rotamer, 357.7; ß turn type I, 380.7; ß turn type II, 397.8; ß turn type II', 385.4; ß turn type VIa, 374.0; ß turn type VIb, 355.0. Key words: proline, ß -turns, free radical, bond dissociation energy, molecular structure, oxidative damage.<

The vibrational circular dichroism (VCD) spectra of 2,5-dioxabicyclo[2.2.1]heptane-3,6-dione 1 (R = H) and the 1,4-dialkyl derivatives, 1 (R = Me) and 1 (R = t-Bu), were calculated by the ab initio magnetic field perturbation (MFP) procedure with a B3LYP/6-31G* force field, and the VCD spectra of the dimethyl and di-t-butyl derivatives were measured in the region 800-1500 cm-1. While the absolute configurations of 1 (R = Me) and 1 (R = t-Bu) could be assigned unambiguously by comparison of the experimental and predicted spectra, there is little obvious correspondence between the spectra of the series of compounds. The VCD spectra are analysed on the basis of operation of a coupled oscillator mechanism involving motions of the polar bonds. In the case of the parent dihydro system, bridgehead C-H bond motions appear to dominate contributions to the VCD of vibrational transitions into which they are mixed.Key words: vibrational circular dichroism (VCD), 2,5-dioxabicyclo[2.2.1]heptane-3,6-dione, dilactones, optical activity.

We report the experimental and predicted absorption and vibrational circular dichroism (VCD) spectra of (1S, 2R, 5S)-(+)-menthol. The harmonic force fields and atomic polar tensors (APTs) were obtained for 10 conformers using density functional theory (DFT) with the Becke3LYP functional and the 6-31G** basis set. The atomic axial tensors (AATs) were obtained with restricted Hartree-Fock (RHF) theory and a 6-31G basis set. VCD intensities were predicted from vibronic coupling theory (VCT). The predicted absorption and VCD spectra based on an equilibrium mixture of conformers corresponded well with the experimental spectra, indicating a reasonable geometry and frequency analysis for each of the conformers. The largest contributions towards the equilibrium population derive from conformers in which the cyclohexane ring occupies a chair conformation, the isopropyl group is directed away from the hydroxyl group, and only the hydroxyl group assumes different conformations.Key words: vibrational circular dichroism (VCD), menthol, conformational analysis.

The experimental VCD spectrum of (2R)-2-methylaziridine has been measured in the region 800–1500 cm−1. The ab initio implementation of the Vibronic Coupling Theory (VCT) of Nafie and Freedman, using the 6-31G*(0.3) basis set, in the common origin and distributed origin gauges and with uniformly and optimally scaled quantum mechanical force fields, is used to investigate the chiroptical properties. VCD spectra are computed for both cis and trans invertomers. The predicted VCD spectrum of 2-methylaziridine (the equilibrium mixture) is dominated by that of the trans diastereomer, not simply because of its greater abundance but because the rotatory strengths of many absorptions in the mid-IR are oppositely signed and of similar magnitude in the two invertomers which differ in absolute configuration at nitrogen. The VCD spectrum of 2-methylaziridine is compared in detail to that of 2-methyloxirane. In the region of the methyl group deformations and CH2 scissor, the theoretical (R)-2-methyloxirane VCD spectrum displays a much closer similarity to the cis-(2R)-2-methylaziridine than to the trans diastereomer.

Ab initio calculations were performed on several aquo complexes of NH2•, and NH3•+, and on monomeric parent species. The geometries were optimized at the HF/6-31 + G* level and the vibrational frequencies were calculated. The total energies and the binding energies of complexes were evaluated at the MP2/6-31 + G* + ZPE level of theory. Gas and aqueous solution phase thermodynamic properites of NH2• and NH3•+ and several other species were calculated. The examination of solution phase properties of the radicals was facilitated by study of the structures and transition energies of aquo complexes. H-bonding interaction energies decreased in the order [Formula: see text] but were generally stronger than σ–σ* interactions involving the unpaired electron. From calculations with the CIS method, the weak absorption observed at 520 nm for aqueous NH2• is confirmed as a 2B1 → 2A1 transition, while the stronger NH2• absorption occurring below 250 nm and the absorption of NH3•+, which rises monotonically below 370 nm, are attributed to solvent-to-solute charge transfer bands. The solution free energies and related E0 values for NH2• and NH3•+ are in agreement with those of Stanbury. The ab initio structure studies show that water protons are bound to N, and proton transfer from solvent in reaction [18], NH2• + e− + H2O → NH3 + OH−, is likely to be the dominant redox reaction of NH2• in alkaline solution. The free energy of solution of NH3•+ is shown to be larger than that of [Formula: see text].

Structural features, configurational stability, and chiroptical properties of the nonplanar amide group in α-lactams were investigated by means of ab initio (6-31 + G*) molecular orbital calculations on (1R)-aziridinone 1, (1R)-1-methylaziridinone 2, (1R,3R)-3-methylaziridinone 3, (1R,3R)-1,3-dimethylaziridinone 4a, its cis diastereomer (1S,3R)-1,3-dimethylaziridinone 4b, and (1R,3R)-3-tert-butyl-1-methylaziridinone 5, and by experimental CD spectra of 1-tert-butyl- and 1-(1′-adamantyl)-substituted 3(R)-3-tert-butylaziridinones 6 and 7. The nitrogen inversion barriers of 4a and 4b are 2.8 and 1.6 kcal mol−1, respectively. The lowest excited singlet state of all of the aziridinones is a valence state (the nO–πCO* transition); the second is a Rydberg state (the nN–3s transition). The signs of the first and second Cotton effects in the CD spectra of the compounds 6 and 7 coincide with the calculated ones for 1 and 2 and the trans isomers 3, 4a, and 5. According to the calculated and experimental data for aziridinones 1–7 as well as to the well-known data for other nonplanar amides, the sign of the first Cotton effects is determined by the intrinsic chirality of the nonplanar amide chromophore and obeys a spiral rule. For cases where the chromophore has the conformation around the N—C(O) bond, which is close to the antiperiplanar, a reverse octant rule is proposed.

The vibrational circular dichroism (VCD) spectra of 2,3-dimethylaziridine 1 and 1,2-dimethylaziridine 2 were measured experimentally and interpreted with the help of ab initio Vibronic Coupling Theory (VCT) both in the common origin (CO) and distributed origin (DO) gauge. The absolute magnitudes of the VCD intensities by the VCT-CO method in the mid-IR range are closer to the experimental measurement. Both VCT-DO and VCT-CO methods, however, predict the same signs for almost all VCD bands. In general, both VCT-DO and VCT-CO methods predict VCD and IR spectra that are both in good agreement with the experimental spectra. The VCT method together with the 6-31G*(0.3) basis set can be employed with confidence in determining the absolute configuration of a chiral molecule. The theoretical and experimental VCD spectra of 1 and 2 were compared with the VCD spectra of the isostructural 2,3-dimethyloxirane and -thiirane. One of the Me rocking motions, in the wave number range 1050–1150 cm−1, was found to serve as a possible marker for the stereochemistry of the molecular skeleton. Two other modes were identified whose Cotton effects (CEs) are characteristic of the local asymmetry, and for which chirality rules were proposed. The first is a methyne vibration, ||CH, which is expected to have a (−) CE at a three-ring centre with (R) absolute configuration. The second is an umbrella motion of a methyl group, which is expected to have a (+) CE when attached to a three-ring centre with (R) absolute configuration.

Ab initio calculations are performed for [Formula: see text] and [Formula: see text] complexes for n = 0–5. For n = 0 and 1, the geometries of the complexes are optimized at the HF/6-31 + G* and MP2/6-31 + G* levels, and the energies are evaluated at the G2 level. For n = 2–5, the geometry optimizations and frequency calculations are carried out at the HF/6-31 + G* level, and the MP2/6-31 + G* energies are calculated at the HF optimized geometries. Basis set superposition errors are corrected by the Boys–Bernardi scheme at the HF/6-31 + G* level. The gas phase thermodynamic properties [Formula: see text] are evaluated as functions of temperature using standard statistical methods. Based on the calculated binding energies and the thermodynamic functions, the incremental changes in enthalpies and free energies, ΔHn and ΔGn, for the gas phase equilibria (H2O)n−1 M+ + H2O → (H2O)nM+ for M+ = NH4+ and NH3•+, are evaluated in comparison with the experimental data for [Formula: see text] the present results suggest conformations for the hydrated complexes observed in the experiments. The total free energy change for filling the first hydration shell is significantly more negative for NH3•+ than for NH4+.

The structures of the major glycine conformers, and several transition state structures, were optimized at HF/6-31G* and HF/6-31 + G* levels of theory and the correlation energies were calculated at MP2/6-31G* and MP2/6-31 + G** levels on these geometries, respectively. The heat of formation of gas phase glycine is calculated to be[Formula: see text]. Thermodynamic properties, [Formula: see text] etc. are calculated as functions of temperature using standard statistical thermodynamic methods. MP2/6-31 + G* optimization was carried out on the zwitterion, found by HF/6-31 + G* optimization to be a local minimum. The results suggest that glycine in the zwitterionic form in the gas phase is not a stationary point. Zwitterionic glycine does not exist in the gas phase.

The structures of the cis and trans invertomers of 2-methylazirdine were optimized at the RHF/6-31G*(0.3) level of theory and the composition of the equilibrium mixture was determined to be trans/cis = 0.71:0.29, in good agreement with the experimental value, 0.66:0.35. The abinitio force field was scaled and a complete assignment of the vibrational spectra of the two conformers is presented. The IR spectrum of 2-methylazirdine was recorded in the vapor phase and in solution (cyclohexane and CCl4). The predicted IR spectrum of the equilibrium mixture agrees very well with the experimental spectrum. The 6-31G*(0.3) basis set is found to provide better geometries and more uniformly scalable force fields than the conventional 6-31G* basis set. Keywords: abinitio force fields, 2-methylaziridine.

Optically pure (S)-cyclopent-2-en-1-ol, [Formula: see text] (c 1.1, CHCl3), and (S)-3-methoxycyclopentene, [Formula: see text] (c 3.86, n-hexane), were prepared from ethyl (1R,2S)-2-hydroxycyclopentanecarboxylate, which is readily available by yeast reduction of ethyl 2-oxocyclopentanecarboxylate. The optical purity of the alcohol was determined from its Mosher ester, and that of the ether by gas chromatography using a Ni-4-Pin column. Keywords: (S)-cyclopent-2-en-1-ol, (S)-3-methoxycyclopentene.

We have implemented at the abinitio level the vibronic coupling formalism for infrared and vibrational circular dichroism (VCD) intensities of Nafie and Freedman. We report here the results of a series of calculations on model systems. Hydrazine and hydrogen peroxide exist in chiral conformations. Although low barriers to racemization preclude the possibility of optical resolution of the parent compounds, the local gauche configuration at the heteroatom bond is preserved in substituted hydrazines and peroxides and these chiral fragments may contribute significantly to the vibrational chiroptical properties of the molecules in which they appear. The calculated VCD rotational strengths for the chiral gauche forms of both molecules suggest that the torsional mode is very intense in the VCD spectrum. In gauche hydrazine of P chirality, the in- and out-of-phase umbrella motions of the nitrogen atoms, ν6 and ν12, respectively, give rise to an intense CD couplet with negative rotational strength to the long wave length side. In hydrazine, all combinations of NH stretches are relatively weak in the IR but the highest frequency mode of b symmetry, ν8, has moderate positive strength. The in- and out-of-phase OOH bends of HOOH behave as a coupled oscillator system, exhibiting a strong bisignate CD pattern. The signals calculated for the OH stretches are not consistent with a coupled oscillator model. The nearly degenerate stretches result in a single band arising from the more intense negative rotational strength of the antisymmetric mode ν5, in HOOH of P chirality. An alternative model, based on induced charge flow along the chirally disposed skeleton (i.e., Nafie and Freedman's 3-bond electronic current model), explains the calculated sign of the antisymmetric mode, ν5. Significant changes in the VCD patterns due to deuterium substitution in both chiral molecules are discussed. Keywords: vibrational circular dichroism (VCD), abinitio, infrared intensities, molecular orbital, vibronic coupling theory, methanol, methanamine, hydrazine, hydroxylamine, hydrogen peroxide.

High level ab initio calculations along with isodesmic reactions have been used to derive a set of self-consistent free energies of formation for carbonate and nitrate species in the gas phase and in aqueous solution. The results show that HCO3· is a strong acid, pKa = –4.1, and that E°(CO3·–/CO32) = 1.23 ± 0.15 V.Key words: carbonate radical anion, theoretical, thermochemistry, acidity, reduction potentials.

Ab initio harmonic force fields were calculated for ethane, propane, dimethyl ether, and cyclobutane at the STO-3G and 3-21G levels. The calculated frequencies, displacement eigenvectors, and calculated infrared absorption intensities were compared as they derive from force constants that were (i) unsealed; (ii) scaled to fit observed vibrational frequencies reported in the literature; (iii) evaluated at the optimized geometries; and (iv) evaluated at structures for which the bond lengths were corrected from the optimized geometries according to published procedures. A total of nine combinations of ab initio force field/reference geometry/G-matrix geometry were investigated for each of the four molecules. The ability of scaling factors as the only variables to predict vibrational parameters from STO-3G and 3-21G force fields was explored. Conditions were examined for which the scaling factors are satisfactorily transferable among different molecules.

The thermal and photochemical decomposition of formyl azide in the Curtius rearrangement has been studied by means of RHF–LCAO–MO–SCF calculations augmented by CI. The lower electronic states of carbonyl azides, carbonyl nitrenes, isocyanates, cyanates, oxazirenes, nitrile oxides (fulminates), and isofulminates are discussed on the basis of the results for formyl azide and the corresponding isomers of formula CHNO. The discovery of two nearly degenerate states of A′′ symmetry for formyl azide which may channel decomposition products directly to both isocyanates and carbonyl nitrenes explains some puzzling features of the photolytic Curtius rearrangement. The interconvertibility of the CHNO isomers (and the RCNO isomers) is discussed in terms of the energetics and intended correlations of the accessible electronic states of these species.

Abinitio restricted Hartree–Fock–Roothaan l.c.a.o.–m.o.–s.c.f. calculations using a Gaussian lobe basis with bond functions have been performed to determine the characteristics of the potential surface for nuclear motions in hydrazine. It was found that in its equilibrium conformation the molecule has a dihedral angle of 95°. The barrier to pyramidal inversion at one nitrogen is 6.1 kcal/mol and the syn and anti rotational barriers are calculated to be 12.0 and 1.6 kcal/mol, respectively. There is a very slight torsional component in the inversion pathway. During rotation over the anti barrier the bond angles contract from their average equilibrium value of 109.5° to 105.3°. This contraction appears to be an important feature of the rotational potential curve. Features of the surface are used to rationalize experimental results in cyclic and acyclic substituted hydrazines.

The static and dynamic structures of the amide derivatives of racemic and (R)-(+)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoic acid (MPTA) with diisopropyl amine (1), meso-2,6-dimethylpiperidine (2), (R)-(−)- and (S)-(+)-2-methylpiperidine (3 and 4, respectively) were investigated by proton nmr spectroscopy. The piperidine rings adopt a single dominant conformation in which the substituent methyl groups occupy axial positions. One of the isopropyl groups of 1 is oriented in the same way as the corresponding side of the piperidine ring of 2–4 but the other (syn to carbonyl oxygen) is turned so that the methyl groups are toward the carbonyl oxygen and the oxygen lies in the plane bisecting the C—C—C angle. Rotation about the amide C(O)—N bond of 1 is accompanied by concurrent rotation about each of the N—iPr single bonds. The free energies of activation of the hindered rotation about the C(O)—N bond in 1–4, 81 kJ/mol, 77 kJ/mol, 77 kJ/mol, and 79 kJ/mol, respectively, are higher than found in most other hindered amides, suggesting that buttressing due to the steric crowding around the amide functionality is felt throughout the rotational pathway.

The 5-endo-trig cyclization reactions of α′-hydroxy α,β-unsaturated carbonyl compounds to form the 3-furanone ring system has been investigated by means of MNDO calculations. In acid medium, the activation energy for ring formation is reduced by protonation of the carbonyl oxygen and by electron-releasing β-substituents, both of which facilitate torsion about the α,β-CC bond. Rotation about the α,β-CC bond is essentially complete when the transition structure is achieved. In reverse ring opening, heterolytic rupture of the C—O bond is aided by prior enolization since induced polarization of the enol π system acts to stabilize the developing cationic centre at the β-carbon. In basic medium, ring closure is hindered by the combined effects of the intrinsic barrier to cyclization and solvation of the intermediate alkoxide. Ring opening in basic medium is prevented by prohibitively high intrinsic barriers except when a strongly electron-releasing group such as p-O(−)-phenyl is at the β-carbon.

The effect of including polarization into a flexible s, p basis set by use of bond functions is studied in the systems H2O, NH3, H2O2, and N2H4. In all cases a decrease and subsequent improvement in calculated bond angles is found. Barriers to nitrogen inversion are also significantly improved. Bond function polarization alone does not account for the anti rotation barrier in H2O2 although it does lead to stabilization of the gauche form relative to the anti form. The effect on molecular charge distributions is to allow movement of charge into the bonding regions. The results indicate that bond functions are an efficient means of introducing polarization into a basis set and lead to an improved agreement between calculated and experimental geometric and energetic parameters.

The three fluorine atoms of N,N-dialkyl amide and chloride derivatives of 2-methoxy-2-phenyl-3,3,3-trifluoropropanoic acid are magnetically nonequivalent below –60 °C and exhibit a clear ABC coupling pattern from which chemical shifts and geminal coupling constants are readily derived. The chemical shifts span a range of about 10 ppm and the geminal coupling constants average about 110 Hz. A five bond coupling of about 5 Hz is observed between the hydrogens of the methoxy group and one of the nonequivalent fluorine atoms of the trifluoromethyl group. Barriers to the hindered rotation about the single bond to the trifluoromethyl group are in the range 36–46 kJ/mol.

A survey of the experimental data on the structures of α-sulfonyl and α-sulfinyl carbanions is presented as an introduction to the present work, a theoretical study of hydrogen methyl sulfoxide (HMSO) and hydrogen methylsulfinyl anion (HMSO−) by nonempirical self consistent field (s.c.f.) calculations using Gaussian basis sets. Calculations on dimethyl sulfoxide (DMSO) and its conjugate base (DMSO−) are also presented and fully justify the choice of HMSO and HMSO− for the detailed work. A conformational energy surface (total energy as a function of rotation about the C—S bond and inversion of the carbanion angle) for HMSO− is presented and used to determine the stereochemical fate of a carbanion generated next to a sulfinyl group. Predictions are made concerning the probable course of proton exchange next to S—O and an explanation is offered for the experimental facts concerning exchange in sulfoxides. A very significant finding is that postulation of d-orbital conjugation is not essential to explain the asymmetry of α-sulfinyl carbanions.

Boron oxide has been found to act as an efficient reagent in the preparation of a number of formate esters by the direct esterification of formic acid with the alcohol. The reaction is most appropriate for primary and secondary alcohols, including unsaturated alcohols. The formate ester so produced is free of contamination by unreacted alcohol.

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