Trans Transition State Research Articles

Analysis of Interconversion between Atropisomers of Chiral Substituted 9,9’‐Bicarbazole

AbstractInterconversion of atropisomers of chiral 3,3’‐di‐tert‐butyl‐9,9’‐bicarbazole linked by a single N−N bond was analyzed by DFT calculations and experiments. The calculations revealed that the trans transition state has a lower energy for the interconversion than the cis transition state. The lowest transition state of interconversion between natural dixiamycins A and B containing a 9,9’‐bicarbazole structure was found to be the trans transition state. The calculations also indicated that degradation through N−N bond cleavage was faster than racemization. Atropisomeric enantiomers of 3,3’‐di‐tert‐butyl‐9,9’‐bicarbazole were resolved by chiral HPLC for the first time, and then racemization and N−N bond cleavage were investigated by heating experiments, showing that racemization did not take place below the degradation temperature.

Reaction pathways and kinetics study on a syngas combustion system: CO + HO2 in an H2O environment.

The reaction between CO and HO2 plays a significant role in syngas combustion. In this work, the catalytic effect of single-molecule water on this reaction is theoretically investigated at the CCSD(T)/aug-cc-pV(D,T,Q)Z and CCSD(T)-F12a/jun-cc-pVTZ levels in combination with the M062X/aug-cc-pVTZ level. Firstly, the potential energy surface (PES) of CO + HO2 (water-free) is revisited. The major products CO2 + OH are formed via a cis- or a trans-transition state (TS) channel and the formation of HCO + O2 is minor. In the presence of water, the title reaction has three different pre-reactive complexes (i.e., RC2: COHO2 + H2O, RC3: COH2O + HO2, and RC4: HO2H2O + CO), depending on the initial hydrogen bond formation. Compared to the water-free process, the reaction barriers of the water-assisted process are reduced considerably, due to more stable cyclic TSs and complexes. The rate constants for the bimolecular reaction pathways CO + HO2, RC2, RC3, and RC4 are further calculated using conventional transition state theory (TST) with Eckart asymmetric tunneling correction. For reaction CO + HO2, our calculations are in good agreement with the literature. In addition, the effective rate constants for the water-assisted process decrease by 1-2 orders of magnitude compared to the water-free one at a temperature below 600 K. In particular, the effective rate constants for the water-assisted and water-free processes are 1.55 × 10-28 and 3.86 × 10-26 cm3 molecule-1 s-1 at 300 K, respectively. This implies that the contribution of a single molecule water-assisted process is small and cannot accelerate the title reaction.

Mechanistic investigation of cis and trans oxidative addition to acetylacetonato-1,5-cyclooctadieneiridium(I)

Density functional theory (DFT) calculations of the oxidative addition of CH3I, as well as Hg(CN)2, to [Ir(acac)(cod)] are described (acac=acetylacetone). Both cis and trans oxidative addition mechanisms are considered and compared to experimental data. The DFT calculated thermodynamically most stable oxidative addition products are trans-[Ir(acac)(cod)(CH3)(I)] and cis-[Ir(acac)(cod)(HgCN)(CN)]. The steric demand of the cod ligand leads to a distorted octahedral trans-[Ir(acac)(cod)(CH3)(I)] complex, with the CCH3-Ir-I angle deviating by more than 20° from 180°, as expected for real octahedral geometry. However, the steric demand of the cod ligand does not lead to any cis transition state for the [Ir(acac)(cod)]+CH3I reaction, rather the trans transition state is energetically favoured, as is generally found for oxidative addition of CH3I to square planar complexes. On the other hand, oxidative addition of Hg(CN)2 to [Ir(acac)(cod)], occurs via a concerted three-centre cis transition state structure. The concerted three-centre cis transition state structure is confirmed by the existence of a ring critical point, as obtained by the Bader’s quantum theory of atoms in molecules analysis of the cis transition state structure. Both trans addition of CH3I to [Ir(acac)(cod)] as well as cis addition of Hg(CN)2 to [Ir(acac)(cod)], are in agreement with experimental observation.

Unimolecular Dissociation of the CH3OCO Radical: An Intermediate in the CH3O + CO Reaction

This work investigates the unimolecular dissociation of the methoxycarbonyl, CH(3)OCO, radical. Photolysis of methyl chloroformate at 193 nm produces nascent CH(3)OCO radicals with a distribution of internal energies, determined by the velocities of the momentum-matched Cl atoms, that spans the theoretically predicted barriers to the CH(3)O + CO and CH(3) + CO(2) product channels. Both electronic ground- and excited-state radicals undergo competitive dissociation to both product channels. The experimental product branching to CH(3) + CO(2) from the ground-state radical, about 70%, is orders of magnitude larger than Rice-Ramsperger-Kassel-Marcus (RRKM)-predicted branching, suggesting that previously calculated barriers to the CH(3)OCO --> CH(3) + CO(2) reaction are dramatically in error. Our electronic structure calculations reveal that the cis conformer of the transition state leading to the CH(3) + CO(2) product channel has a much lower barrier than the trans transition state. RRKM calculations using this cis transition state give product branching in agreement with the experimental branching. The data also suggest that our experiments produce a low-lying excited state of the CH(3)OCO radical and give an upper limit to its adiabatic excitation energy of 55 kcal/mol.

Mechanisms of Staudinger reactions within density functional theory.

The Staudinger reactions of substituted phosphanes and azides have been investigated by using density functional theory. Four different initial reaction mechanisms have been found. All systems studied go through a cis-transition state rather than a trans-transition state or a one-step transition state. The one-step pathway of the phosphorus atom attacking the substituted nitrogen atom is always unfavorable energetically. Depending on the substituents on the azide and the phosphane, the reaction mechanism with the lowest initial reaction barrier can be classified into three categories: (1). like the parent reaction, PH(3) + N(3)H, the reaction goes through a cis-transition state, approaches a cis-intermediate, overcomes a PN-bond-shifting transition state, reaches a four-membered ring intermediate, dissociates N(2) by overcoming a small barrier, and results in the final products: N(2) and a phosphazene; (2). once reaching the cis-intermediate, the reaction goes through the N(2)-eliminating transition state and produces the final products; (3). the reaction has a concerted initial cis-transition state, in which the phosphorus atom attacks the first and the third nitrogen atoms of the azide simultaneously and reaches an intermediate, and then the reaction goes through similar steps of the first reaction mechanism. In contrast to the previous predictions on the relative stability of the unsubstituted cis-configured phosphazide intermediate and the unsubstituted trans-configured phosphazide intermediate, the total energy of the substituted trans-configured phosphazide intermediate is close to that of the substituted cis-configured phosphazide intermediate. The preference of the initial cis-transition state reaction pathway is thoroughly discussed. The relative stability of the cis- and the trans-intermediates is explored and analyzed with the aid of molecular orbitals. The effects of substituents and solvent effects on the reaction mechanisms of the Staudinger reactions are discussed in detail.

Substituent effects and nearly degenerate transition states: rational design of substrates for the tandem Wolff-Cope reaction.

The substrate scope for a ketene-assisted Cope (tandem Wolff-Cope) reaction is elucidated from first-principles quantum mechanics. An alternate pathway (trans) leading to an undesired and unstable product lies perilously close ( approximately 2.5 kcal/mol) to the primary (cis) reaction pathway; this near-degeneracy arises from preferential ketene stabilization of a radicaloid trans transition state over an aromatic cis transition state. Normally, substitution at "forbidden" sites causes the alternate pathway to be favored and the reaction to fail, but using simple conformational analysis principles we design substrates that defy this rule.

Structural definition of the active site and catalytic mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase.

X-ray crystal structures of L-3,4-dihydroxy-2-butanone-4-phosphate synthase from Magnaporthe grisea are reported for the E-SO(4)(2-), E-SO(4)(2-)-Mg(2+), E-SO(4)(2)(-)-Mn(2+), E-SO(4)(2)(-)-Mn(2+)-glycerol, and E-SO(4)(2)(-)-Zn(2+) complexes with resolutions that extend to 1.55, 0.98, 1.60, 1.16, and 1.00 A, respectively. Active-site residues of the homodimer are fully defined. The structures were used to model the substrate ribulose 5-phosphate in the active site with the phosphate group anchored at the sulfate site and the placement of the ribulose group guided by the glycerol site. The model includes two Mg(2+) cations that bind to the oxygen substituents of the C2, C3, C4, and phosphate groups of the substrate, the side chains of Glu37 and His153, and water molecules. The position of the metal cofactors and the substrate's phosphate group are further stabilized by an extensive hydrogen-bond and salt-bridge network. On the basis of their proximity to the substrate's reaction participants, the imidazole of an Asp99-His136 dyad from one subunit, the side chains of the Asp41, Cys66, and Glu174 residues from the other subunit, and Mg(2+)-activated water molecules are proposed to serve specific roles in the catalytic cycle as general acid-base functionalities. The model suggests that during the 1,2-shift step of the reaction, the substrate's C3 and C4 hydroxyl groups are cis to each other. A cis transition state is calculated to have an activation barrier that is 2 kcal/mol greater than that of the trans transition state in the absence of the enzyme.

Six-dimensional tunneling dynamics of internal rotation in hydrogen peroxide molecule and its isotopomers

The six-dimensional torsion-vibration Hamiltonian of the H2O2 molecule and its H/D- and 18O/16O-isotopomers is derived. The Hamiltonian includes the kinetic energy operator, which depends on the tunneling coordinate, and the potential energy surface represented as a quartic polynomial with respect to the small-amplitude transverse coordinates. Parameters of the Hamiltonian were obtained from DFT calculations of the equilibrium geometries, eigenvectors, and eigenfrequencies of normal vibrations at the stationary points corresponding to the ground state and both the cis- and trans-transition states, carried out with the B3LYP density functional and 6-311+G(2d,p) basis set. The quantum dynamics problem is solved using the perturbative instanton approach generalized for the excited states situated above the barrier top. Vibration-tunneling spectra are calculated for the ground state and low-lying excited states with energies below 2000 cm–1. Strong kinematic and squeezed potential couplings between the large-amplitude torsional motion and bending modes are shown to be responsible for the vibration-assisted tunneling and for the dependence of tunneling splittings on the quantum numbers of small-amplitude transverse vibrations. Mode-specific isotope effects are predicted.

Ab initio modelling of peptide biosynthesis

Ab initio calculations (HF/3–21G) have been used to study the mechanism of peptide biosynthesis ( R 1 COOR 2 + R 3 NH 2 → R 1 CONHR 3 + R 2 OH). Two or four water molecules are included to represent the primary solvent shell. The studies show that the reaction proceeds via a gauche or trans transition state if it starts from the reactant's gauche or trans complex. The energy barrier of the reaction with two water molecules is calculated to be 27.96 ( gauche) or 26.85 kcal mol −1 ( trans), while that of the reaction with four water molecules is only 14.82 ( gauche) or 13.21 kcal mol −1 ( trans).

An ab initio study of the dissociation of HNCO in the S1 electronic state

Regions of the S1 potential energy surface of HNCO relevant to N–H and C–N bond photodissociation have been investigated with ab initio calculations. Geometries of minima and transition states on S1 as well as those of the product photofragments and the HNCO ground state have been optimized with the CASSCF method, and their energies calculated with MRSDCI and CASPT2 methods. Deep planar trans and cis minima exist on the S1 surface, and are connected by transition states for isomerization. The S0→S1 electronic transition is brighter for trans configurations than for cis, and the initial excitation and dynamics are most likely to proceed through trans configurations. The N–H fission on S1 has a substantial barrier; it occurs more easily through the planar cis transition state, which is about 20 kcal/mol above the dissociation threshold, than through the trans transition state. The C–N fission on S1 can take place both via the planar trans and the planar cis transition state with a low barrier over the dissociation threshold; the reverse barrier is estimated to be a few kcal/mol.

Spin-coupled description of organic reaction pathways: the cycloaddition reaction of two ethene molecules

Spin-coupled (SC) theory is applied to the description of one of the simplest cycloaddition reactions: the orbital-symmetry-forbidden ground-state dimerization of two ethene molecules to cyclobutane: 2 C2H4→ C4H8. The aim is to show that the easy-to-visualize and easy-to-interpret features of the SC wavefunction, namely, the form of the valence orbitals and the nature of the spin-coupling pattern within the active space, provide important guiding information, which helps make qualitative predictions about the reaction pathway without carrying out a detailed investigation of the related potential surface.It is demonstrated that the SC orbitals from a four-orbital active space, corresponding to the forbidden concerted face-to-face approach, bend outwards of the C4H8 ring, which suggests that optimum overlap can be achieved only through a non-concerted approach, passing either through a cis, or through a trans transition state. A re-examination of the size of the active space needed for the proper valence-bond (VB) type analysis of the reaction shows that eight valence orbitals are required in order to achieve correlated descriptions of the two carbon–carbon double bonds in the reacting ethenes, of the three carbon–carbon single bonds and of the two unpaired electrons in the tetramethylene biradical intermediates, as well as of the four equivalent carbon–carbon single bonds in the final product, cyclobutane. SC calculations for the model reaction pathways leading to the formation of cis and trans tetramethylene biradicals, performed within an eight-orbital active space indicate that the trans pathway has a lower potential barrier and leads to a biradical lower in energy; the minimum corresponding to the formation of a cis biradical is rather shallow. The electronic structure of the tetramethylene biradicals is rationalized in easily conceivable terms, such as orbital shapes and spin-coupling patterns.

Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and ab initio study of hydride‐ion transfer between the NADH analogue, 1‐methyl‐dihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase

AbstractAs part of a study of factors controlling biological redox reactions of nicotinamide cofactors [nicotinamide adenine dinucleotide (phosphate) NAD(P)H], we have investigated the effect on a model reaction of the conformational state (cis or trans) of the carboxamide side chain, using quantum chemical methods. The reaction is that for the enzyme dihydrofolate reductase between the NADPH analogue, 1‐methyl‐dihydronicotinamide, and the protonated forms of the folate and dihydrofolate substrate analogues, pyrazine and dihydropyrazine. Some calculations on pterin and dihydropterin substrate analogues were also carried out in order to gauge the effects of inter‐ring coupling. The influence of carboxamide side‐chain conformation of nicotinamide on the energetics of the hydride‐ion transfer, and on the structures of the transition states and stable intermolecular‐interaction complexes, are examined as a function of the orientation of approach of the reactants. These approach geometries include those corresponding to the observed binding of cofactor and either substrate or inhibitor in the enzyme active site. Reactant, product, reactants‐complex, and transition‐state geometries were optimized at the semiempirical AM1 level, while ab initio SCF/STO‐3G and SCF/3‐21G single‐point calculations were carried out at the AM1 optimized geometries for all species, as well as full geometry optimizations for isolated reactants and products. The results show that reactants‐complex and transition‐state energies are lower for the trans conformer of dihydronicotinamide than for the cis conformer, due to more favorable H‐bonding or electrostatic interactions with the protonated substrate. Also, consideration of the structural parameters, including reaction coordinate bond lengths, ring geometries, and charge distributions, indicate that the trans transition states are more product‐like than those for the cis. For the (trans) approaches corresponding to the enzymic orientation for substrate, the intermolecular interaction for the folate reaction lacks the stabilizing influence of the formal H‐bond which is present for the dihydrofolate reaction, and consequently the reactants‐complex and transition state are less stable.

Disulfide conformational analysis: The nature of the S-S rotation barrier

Previous DNMR measurements for a series of bulky disulfides led to the conclusion that rotation about the S-S bond occurs preferentially through the cis transition state. To investigate this conclusion and to study the conformational properties of disulfides in general, we have applied Allinger's force field to a series of dialkyl disulfides generated by homologating dimethyl disulfide to di-t-butyl disulfide. The optimized ground state geometries evidence a gradual increase in the CS-CS dihedral angle from 83 to 114° and indicate that increased substituent bulk drives the disulfide system in the direction of the trans rotational maximum. Explicit calculation of barrier heights yields ΔE( trans) < ΔE( cis) in every case. Furthermore the energy gap, ΔΔE( cis-trans), increases sharply as substituent size grows. This trend results from a rapid rise in the cis barrier and a small drop in the trans one. A rotation-inversion pathway is ruled out and it is concluded that disulfide conformational isomerization occurs by way of the trans transition state. p ]Torsion about the S-C bonds for several t-Bu substituted disulfides is considered. A strongly coupled alkyl-t-Bu rotation is observed computationally in accord with Nelander and Sunner's speculations concerning a “cogwheel effect.” ΔG† trends for S-S rotation are discussed in connection with the latter. p ]Finally a ΔH(S-S) parameter is derived. Heats of formation and strain energies for dialkyl disulfides are calculated.

Studies on the components in NTU shale oil. 3. The Hofmann degradation of alkylpiperidines

The Hofmann degradation of quaternary ammonium compounds was examined with 2-alkyl-, 2, 4-dialkyl-, and 2, 4, 6-trialkyl-piperidinium iodides. Thermal decompotion of 2-pentylpiperidinium hydroxide (IV6) produced 5-dimethylamino-1-decene (B) (47%), 1-dimethylamino-4-decene (C) (38%), and 1-dimethylamino-5-decene (D) (15%) (Table II). Elimination generally occurs preferentially in the piperidine ring, rather than in the 2-alkyl chain, except when the alkyl is a methyl group. This result may be interpreted as being due to the steric effect in the planer trans transition state during formation of olefins from quaternary bases.