Ab initio studies of structural features not easily amenable to experiment: Part 6. Quantitative estimate of the effect of bond delocalization on structure and hyperconjugative interaction of the amide group

The structural changes, which occur in the amide unit when the NH₂-group is twisted out of plane by rotation about the NC bond, have been determined by comparing the completely relaxed ab initio geometries of planar and perpendicular formamide and acetamide. In the perpendicular conformation, in which the π-electron amide resonance is uncoupled, the NC bond distance is 0.080.09 Å longer than in the planar form; the CO bond distance is about 0.01 Å shorter; NH distances are about 0.01 Å longer; and HNC angles are 510° smaller, whereas the CNO angle is relatively constant. Because of the apparent invariance of CH₃-hyperconjugation effects in planar and perpendicular acetamide, it is tentatively postulated that anomeric orbital interactive effects (involving the lone pair on NH, the CO π-electron pair and antibonding π*-group-orbitals on C(α) in NHC(HR)C(O)), which should be an important factor in determining peptide chain conformation, do not vary significantly with small deviations from amide group planarity.     

Isomerization of azomethine- and azo-compounds and their protonated species

Barriers of rotation and inversion, respectively, have been calculated for the species H₂CNH (I), H₂CNCH₃ (II), NHNH (III), NHNCH₃ (IV) and their protonated species. For any unprotonated molecule the barrier of inversion is consistently lower than the barrier of rotation. Tile inversion barriers are: 27.8 (I), 23.8 (II), 51.9 (III) and 46.1 (IV) kcal/mole. In the case of azomethine species, protonation results in an increased rotational barrier (from 50.8 to 74.7 kcal/mole for II). In the case of azo species barriers of inversion are lowered on protonation (from 51.9 to 30.1 for II and from 46.1 to 24.4 kcal/mole for IV). All barriers are given with reference to the trans-isomer (azo). Proton affinities for the azomethine species are higher than those of the corresponding azo species (223.3 for 1, 199.9 kcal/mole for II).     

Force field parameters for sulfates and sulfamates based on ab initio calculations: Extensions of AMBER and CHARMm fields

Ab initio self-consistent field (SCF) Hartree-Fock calculations of sulfates R? O? SO₃(?1) (R = Me, Et, i-Pr) and sulfamates R? NHSO₃(?1) (R = H, Me, Et, i-Pr) were performed at the 4-31G(*S*N) //3-21G(*S*N) basis set levels, where asterisks indicate d functions on sulfur and nitrogen atoms. These standard levels were determined by comparing calculation results with several basis sets up to MP2/6-31G*//6-31G*. Several conformations per compound were studied to obtain molecular geometries, rotational barriers, and potential derived point charges. In methyl sulfate, the rotational barrier around the C? O bond is 1.6 kcal/mol at the MP2 level and 1.4 kcal/mol at the standard level. Its ground state has one of three HCOS torsion angles trans and one of three COSO torsion angles trans. Rotation over 60° around the single O? S bond in the sulfate group costs 2.5 kcal/mol at the MP2 and 2.1 kcal/mol at the standard level. For ethyl sulfate, the calculated rotational barrier in going from the ground state, which has its CCOS torsion angle trans, to the syn-periplanar conformation (CCOS torsion angle cis) is 4.8 kcal/mol. However, a much lower barrier of 0.7 kcal/mol leads to a secondary gauchelike conformation about 0.4 kcal/mol above the ground state, with the CCOS torsion angle at 87.6°. Again, one of the COSO torsion angles is trans in the ground state, and the rotational barrier for a 60° rotation of the sulfate group amounts to 1.8 kcal/mol. For methyl sulfamate, the rotational barriers are 2.5 kcal/mol around the C? N bond and 3.3 kcal/mol around the N? S bond. This is noteworthy because sulfamate itself has a calculated rotational barrier around the N? S bond of only 1.7 kcal/mol. These and other data were used to parameterize the well-known empirical force fields AMBER and CHARMm. When the new fields were tested by means of vibrational frequency calculations at the 6-31G*//6-31G* level for methyl sulfate, sulfamate, and methyl sulfamate ground states, the frequencies compared favorably with the AMBER and CHARMm calculated frequencies. The transferability of the force parameters to β-D -glucose-6-sulfate and isopropyl sulfate appears to be better than to isopropyl sulfamate. © 1995 by John Wiley & Sons, Inc.     

Electronic structure and conformational properties of the amide linkage Part 5. Internal rotation and inversion in 1-formylaziridine

Internal rotation and nitrogen inversion in 1-formylaziridine (1) have been investigated by quantum mechanical (ab initio and MNDO) calculations, especially with respect to the variation of the geometry of the aziridine ring. While conformational stability is mainly determined by the n(N)/π(CO) interaction, the bond lengths within the ring are affected by the amount of interaction between the π(CO) orbital and the Walsh orbital ω_A. To separate the two types of interaction, calculations were also performed on formylcyclopropane (9). The torsional potential of 1 has a minimum close to the perpendicular conformation 1b. The two bisected conformations, 1a and 1c, are transition states for internal rotation. For nitrogen inversion, a barrier of 1.44 kcal mol⁻¹ (ab initio) was calculated. Calculations on 1-cyanoaziridine (7) gave inversion barriers of 5.81 (ab initio) and 12.31 kcal mol⁻¹ (MNDO). Probably due to methodical reasons the ab initio values seem to be too low, as calculations with different basis sets for aziridine indicate.     

Ab initio calculations including electron correlation,and mindo/3 calculations on the system C2H+7

Ab initio SCF and CEPA PNO calculations have been performed together with MINDO/3 calculations on the system C₂H⁺₇. In agreement with experimental assignment, but in contradiction to MINDO/3 results, the ab initio methods show the CC protonated structure to be more stable than the CH protonated structure. The energy difference is 8.5 kcal/mol at the SCF level and 6.3 kcal/mol with inclusion of electron correlation. Additionally, ΔH⁰₃₀₀ for the reaction C₂H⁺_s + H₂ = C₂H⁺₇ and the proton affinity of ethane are computed.     

Conformational Study of 8—C—glucosyl—prunetin by Dynamic NMR Spectroscopy

By means of variable temperature NMR spectra,conformation of 8-C-glucosyl prunetin, isolated from the leaves of Dalbergia hainanensis (Leguminosae), was studied. The restricted rotation around the C(sp^3)-C(sp^2) bond in the C-glucosides isoflavonoid results in two main conformers (syn and anti). With the help of MM calculation, the preferred conformation A has H-1″ gauche to the 7-OCH3. The barrier to rotation was 18.1 kcal/mol. This result agrees with the calculated value 16.2 kcal/mol of free energy of activation for the interconversion between the conformers.     

Proton migration and tautomerism in protonated triglycine.

Proton migration in protonated glycylglycylglycine (GGG) has been investigated by using density functional theory at the B3LYP/6-31++G(d,p) level of theory. On the protonated GGG energy hypersurface 19 critical points have been characterized, 11 as minima and 8 as first-order saddle points. Transition state structures for interconversion between eight of these minima are reported, starting from a structure in which there is protonation at the amino nitrogen of the N-terminal glycyl residue following the migration of the proton until there is fragmentation into protonated 2-aminomethyl-5-oxazolone (the b(2) ion) and glycine. Individual free energy barriers are small, ranging from 4.3 to 18.1 kcal mol(-)(1). The most favorable site of protonation on GGG is the carbonyl oxygen of the N-terminal residue. This isomer is stabilized by a hydrogen bond of the type O-H.N with the N-terminal nitrogen atom, resulting in a compact five-membered ring. Another oxygen-protonated isomer with hydrogen bonding of the type O-H.O, resulting in a seven-membered ring, is only 0.1 kcal mol(-)(1) higher in free energy. Protonation on the N-terminal nitrogen atom produces an isomer that is about 1 kcal mol(-)(1) higher in free energy than isomers resulting from protonation on the carbonyl oxygen of the N-terminal residue. The calculated energy barrier to generate the b(2) ion from protonated GGG is 32.5 kcal mol(-)(1) via TS(6-->7). The calculated basicity and proton affinity of GGG from our results are 216.3 and 223.8 kcal mol(-)(1), respectively. These values are 3-4 kcal mol(-)(1) lower than those from previous calculations and are in excellent agreement with recently revised experimental values.     

MINDO/3 Calculation of carbocation heats of formation

Heats of formation calculated by MINDO /3 are reported for 42 carbocations for which experimental heats of formation have been published. Errors associated with these calculations can be large, with an overall range of ±13 kcal/mol. Correction of systematic errors in the MINDO /3 calculations by means of hydrocarbon models and isodesmic relationships results in a reduction in the range of errors to ±8 kcal/mol. Comparison with experimental heats of reaction of hydride transfer equilibria minimizes experimental errors and gives an average absolute error of 2 kcal/mol with a range of ±3 kcal/mol.     

A semiempirical study of the optimized ground and excited state potential energy surfaces of retinal and its protonated Schiff base.

The electronic ground and first excited states of retinal and its Schiff base are optimized for the first time using the semiempirical AM1 Hamiltonian. The barrier for rotation about the C(11)-C(12) double bond is characterized by variation of both the twist angle delta(C(10)-C(11)-C(12)-C(13)) and the bond length d(C(11)-C(12)). The potential energy surface is obtained by varying these two parameters. The calculated ground state rotational barrier is equal to 15.6 kcal/mol for retinal and 20.5 kcal/mol for its Schiff base. The all-trans conformation is more stable by 3.7 kcal/mol than the 11-cis geometry. For the first excited state, S(1,) the 90 degrees twisted geometry represents a saddle point for retinal with the rotational barrier of 14.6 kcal/mol. In contrast, this conformation is an energy minimum for the Schiff base. It can be easily reached at room temperature from the planar minima since it is separated from them by a barrier of only 0.6 kcal/mol. The 90 degrees minimum conformation is more stable than the all-trans by 8.6 kcal/mol. We are thus able to present a reaction path on the S(1) surface of the retinal Schiff base with an almost barrier-less geometrical relaxation into a twisted minimum geometry, as observed experimentally. The character of the ground and first excited singlet states underscores the need for the inclusion of double excitations in the calculations.     

(η5-C5H5)(Ph2PCH2CH2PPH2)RuCH2+ AsF6−. Spectral Characterization and measurement of the barrier to methylene rotation

The electrophilic methylene complex (η⁵-C₅H₅)(Ph₂PCH₂CH₂PPh₂)RuCH₂⁺ (1) has been characterized by ¹³C and variable-temperature ¹H NMR spectroscopy and exhibits a vertical orientation of the methylene group with a barrier for rotation about the rutheniumcarbon double bond of 10.9 kcal/mol.     

An ab initio study of the electronic structure of diimide

Ab initio calculations on the structure and geometry of the three isomers of N₂H₂ (trans-diimide, cis-diimide, and 1,1-dihydrodiazine) were performed both on HF and CI level using gaussian basis sets with polarization functions. The trans and cis isomers have singlet ground states; the trans isomer is found to be lower in energy than the cis isomer by 6.9 kcal/mol (HF) and 5.8 kcal/mol (CI), respectively. The barrier for the trans-cis isomerization is predicted to be 56 (HF) and 55 (CI) kcal/mol. H₂ N=N has a triplet ground state with a non-planar equilibrium geometry and a rather long NN bond of 1.34 Å. Its lowest singlet state, however, is planar with an NN double bond of 1.22 Å; it is found to lie about 3 kcal/mol above the triplet and 26 kcal/mol above the singlet ground state of trans-diimide.     

First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine

We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine. The significant decrease of the free energy barrier, approximately 4 kcal/mol, is attributed to the intramolecular acid catalysis of the methyl ester hydrolysis of protonated cocaine, because the transition state structure is stabilized by the strong hydrogen bond between the carbonyl oxygen of the methyl ester moiety and the protonated tropane N. The relative magnitudes of the free energy barriers calculated for different pathways of the ester hydrolysis of protonated chair cocaine are consistent with the experimental kinetic data for cocaine hydrolysis under physiologic conditions. Similar intramolecular acid catalysis also occurs for the benzoyl ester hydrolysis of (protonated) boat cocaine in the physiologic condition, although the contribution of the intramolecular hydrogen bonding to transition state stabilization is negligible. Nonetheless, the predictability of the intramolecular hydrogen bonding could be useful in generating antibody-based catalysts that recruit cocaine to the boat conformation and an analog that elicited antibodies to approximate the protonated tropane N and the benzoyl O more closely than the natural boat conformer might increase the contribution from hydrogen bonding. Such a stable analog of the transition state for intramolecular catalysis of cocaine benzoyl-ester hydrolysis was synthesized and used to successfully elicit a number of anticocaine catalytic antibodies.     

Gas-phase structure of protonated histidine and histidine methyl ester: combined experimental mass spectrometry and theoretical ab initio study

Gas-phase H/D exchange experiments with CD3OD and D2O and quantum chemical ab initio G3(MP2) calculations were carried out on protonated histidine and protonated histidine methyl ester in order to elucidate their bonding and structure. The H/D exchange experiments show that both ions have three equivalent fast hydrogens and one appreciably slower exchangeable hydrogen assigned to the protonated amino group participating in a strong intramolecular hydrogen bond (IHB) with the nearest N(sp2) nitrogen of the imidazole fragment and to the distal ring NH-group, respectively. It is taken for granted that the proton exchange in the IHB is much faster than the H/D exchange. Unlike in other protonated amino acids (glycine, proline, phenylalanine, tyrosine, and tryptophan) studied earlier, the exchange rate of the carboxyl group in protonated histidine is slower than that of the amino group. The most stable conformers and the enthalpies of neutral and protonated histidine and its methyl ester are calculated at the G3(MP2) level of theory. It is shown that strong intramolecular hydrogen bonding between the amino group and the imidazole ring nitrogen sites is responsible for the stability and specific properties of the protonated histidine. It is found that the proton fluctuates between the amino and imidazole groups in the protonated form across an almost vanishing barrier. Proton affinity (PA) of histidine calculated by the G3(MP2) method is 233.2 and 232.4 kcal mol(-1) for protonation at the imidazole ring and at the amino group nitrogens, respectively, which is about 3-5 kcal mol(-1) lower than the reported experimental value.     

Barriers to rotation in methyl formate by dynamic NMR spectroscopy and barriers to 1,3 oxygen-to-oxygen migration in methyl formate and trifluoromethyl formate by ab initio calculations

Free-energy barriers of 9.85 and 11.91 +/- 0.15 kcal/mol at -70.8 degrees C were found by dynamic NMR spectroscopy for the E-to-Z and Z-to-E conversions, respectively, of methyl formate (1) enriched in 13C to 99% for the carbonyl carbon [methyl formate 13C (2)]. These barriers are higher than the literature values reported for -53 degrees C. The free-energy barrier to 1,3 oxygen-to-oxygen migration of the methyl group in methyl formate was determined by ab initio calculations at several levels. The value of 58.7 kcal/mol obtained at the MP2/6-311+G (df,pd) level was compared to a literature barrier for this process (MINDO/3) and to barriers for related compounds. A free-energy barrier of 63.0 kcal/mol for the oxygen - to - oxygen migration of the CF3 group in trifluoromethyl formate (3) was calculated at the MP2/6-31+G level.     

Unusually low barrier to carbamate C-N rotation

The barrier for rotation about an N-alkylcarbamate C(carbonyl)-N bond is around 16 kcal/mol. In the case of an N-phenylcarbamate, the rotational barrier is lowered to 12.5 kcal/mol, but with N-(2-pyrimidyl)carbamates the barriers are so low (<9 kcal/mol) that the syn and anti rotamers cannot be observed as separate signals by 500 MHz NMR spectroscopy at 183 K. X-ray and computational data show that the N-(2-pyrimidyl) carbamates have C(carbonyl)-N bonds that are on average 0.03 A longer than for related N-phenylcarbamates. The computational results trace the origin of the effect to increased single bond character for the C(carbonyl)-N bond due to the increased electron-withdrawing ability of the pyrimidyl ring.     

An ab initio SCF and CI study of ketene imine

The electronic structures of the ground and excited states of ketene imine (_H^HCCNH) have been studied by ab initio SCF and CI calculations. The nucleophilic nature of the β carbon with respect to nitrogen has been discussed using calculated electrostatic potentials and by calculated energy differences between the parent and protonated species. The electronically excited ¹A″ and ³A″ states are found to be almost degenerate.     

Experimental and theoretical studies on the thermal decomposition of heterocyclic nitrosimines

A series of substituted 2-nitrosiminobenzothiazolines (2) were synthesized by the nitrosation of the corresponding 2-iminobenzothiazolines (6). Thermal decomposition of 2a--f and of the seleno analogue 7 in methanol and of 3-methyl-2-nitrosobenzothiazoline (2a) in acetonitrile, 1,4-dioxane, and cyclohexane followed first-order kinetics. The activation parameters for thermal deazetization of 2a were measured in cyclohexane (Delta H(++) = 25.3 +/- 0.5 kcal/mol, Delta S(++) = 1.3 +/- 1.5 eu) and in methanol (Delta H(++) = 22.5 +/- 0.7 kcal/mol, Delta S(++) = -12.9 +/- 2.1 eu). These results indicate a unimolecular decomposition and are consistent with a proposed stepwise mechanism involving cyclization of the nitrosimine followed by loss of N(2). The ground-state conformations of the parent nitrosiminothiazoline (9a) and transition states for rotation around the exocyclic C==N bond, electrocyclic ring closure, and loss of N(2) were calculated using ab initio molecular orbital theory at the MP2/6-31G* level. The calculated gas-phase barrier height for the loss of N(2) from 9a (25.2 kcal/mol, MP4(SDQ, FC)/6-31G*//MP2/6-31G* + ZPE) compares favorably with the experimental barrier for 2a of 25.3 kcal/mol in cyclohexane. The potential energy surface is unusual; the rotational transition state 9a-rot-ts connects directly to the orthogonal transition state for ring-closure 9aTS. The decoupling of rotational and pseudopericyclic bond-forming transition states is contrasted with the single pericyclic transition state (15TS) for the electrocyclic ring-opening of oxetene (15) to acrolein (16). For comparison, the calculated homolytic strength of the N--NO bond is 40.0 kcal/mol (MP4(SDQ, FC)/6-31G*//MP2/6-31G* + ZPE).     

The aromatic character of silacyclopropenes

Minimum energy geometries for silacyclopropene, 1,1-difluoro-,1,1-dimethyl,2,3-dimethy1-, and tetramethylsilacyclopropene have been calculated using the CND0/2 approximation. The calculations predict a remarkably small ring CSiC bond angle of about 43.6°. The average ring CC bond length is predicted to be 1.380 Å, slightly shorterthan the CC bond length in aromatic rings. Substantial stabilization of the compounds arises from π interaction between the CC double bond and acceptor orbitals on silicon giving significant aromatic character to the molecules.     

Evaluation of MINDO/3 calculated structures. II. Branching errors in alkanes and cycloalkanes

MINDO/3 calculations have been carried out for a series of branched chain alkanes in order to assess effects of branching on calculated geometries and heats of formation (ΔH_f). With vicinal branching, MINDO/3 calculates the central C? C bond to be too long. Bond angles are also found to be distorted. Errors in calculated heats of formation are large when geminal branching is present and significant with vicinal branching. Branching error corrections for ΔH_f have been derived and applied to a separate series of branched acyclic and cyclic compounds. For the test sample, application of the branching error corrections gave calculated structures of acyclic branched hydrocarbons with heats of formation having an average absolute error of 1.3 kcal/mole rather than 17.3 kcal/mole before correction. Cyclic branched hydrocarbons are shown to be less well corrected. Calculations of heats of reaction have also been carried out for some isomerization and cyclization reactions using the MINDO/3 and MNDO methods. It is clear from the comparisons that MNDO calculations give less severe errors for highly branched compounds but the errors are still substantial. For prediction of heats of reaction, the error-corrected calculations are shown to be superior to the “raw” calculations obtained by MINDO/3 or MNDO.     

The silafulvene: a potentially stable compound containing a double carbonsilicon bond

Two conformations of dimethylsilafulvene are calculated via a CNDO/2 procedure. One of them is planar while in the other the CH₃SiCH₃ plane is perpendicular to the cyclopentadienyl ring plane. The conformation energies differ by 19.8 kcal/mol.