Transition State TS2 Research Articles

Insights into the Mechanism of O2 Formation and Release from the Mn4O4L6 “Cubane” Cluster

To probe photoinduced water oxidation catalyzed by the Mn₄O₄L₆ cubane clusters, we have computationally studied the mechanism and controlling factors of the O₂ formation from the [Mn₄O₄L₆] catalyst, 6. It was demonstrated that dissociation of an L = H₂PO₂⁻ ligand from 6 facilitates the direct O-O bond formation that proceeds with a 28.3 (33.4) kcal/mol rate-determining energy barrier at the transition state TS1. This step (the O-O single bond formation) of the reaction is a two-electron oxidation/reduction process, during which two oxo ligands are transformed into to μ²:η²-O₂²⁻ unit, and two ("distal") Mn centers are reduced from the 4+ to the 3+ oxidation state. Next two-electron oxidation/reduction occurs by "dancing" of the resulted O₂²⁻ fragment between the Mn¹ and Mn²/Mn(2')-centers, keeping its strong coordination to the Mn(1')-center. As a result of this four-electron oxidation/reduction process Mn centers of the Mn₄-core of I transform from {Mn¹(III)-Mn(1')(III)-Mn²(IV)-Mn(2')(IV)} to {Mn¹(II)-Mn(1')(II)-Mn²(III)-Mn(2')(III)} in IV. In other words, upon O₂ formation in cationic complex [Mn₄O₄L₅](+), I, all four Mn-centers are reduced by one electron each. The overall reaction I → TS1 → II → III → TS2 → IV → TS3 → V → VI + O₂ is found to be exothermic by 15.4 (10.5) kcal/mol. We analyze the lowest spin states and geometries of all reactants, intermediates, transition states, and products of the targeted reaction.

The Pt-Catalyzed Ethylene Hydroamination by Aniline: A Computational Investigation of the Catalytic Cycle

A full QM DFT study without system simplification and with the inclusion of solvation effects in aniline as solvent has addressed the addition of aniline to ethylene catalyzed by PtBr(2)/Br(-). The resting state of the catalytic cycle is the [PtBr(3)(C(2)H(4))](-) complex (II). A cycle involving aniline activation by N-H oxidative addition was found energetically prohibitive. The operating cycle involves ethylene activation followed by nucleophilic addition of aniline to the coordinated ethylene, intramolecular transfer of the ammonium proton to the metal center to generate a 5-coordinate (16-electron) Pt(IV)-H intermediate, and final reductive elimination of the PhNHEt product. Several low-energy ethylene complexes, namely trans- and cis-PtBr(2)(C(2)H(4))(PhNH(2)) (IV and V) and trans- and cis-PtBr(2)(C(2)H(4))(2) (VII and VIII) are susceptible to aniline nucleophilic addition to generate zwitterionic intermediates. However, only [PtBr(3)CH(2)CH(2)NH(2)Ph](-) (IX) derived from PhNH(2) addition to II is the productive intermediate. It easily transfers a proton to the Pt atom to yield [PtHBr(3)(CH(2)CH(2)NHPh)](-) (XX), which leads to rate-determining C-H reductive elimination through transition state TS(XX-L) with formation of the σ-complex [PtBr(3)(κ(2):C,H-HCH(2)CH(2)NHPh)](-) (L), from which the product can be liberated via ligand substitution by a new C(2)H(4) molecule to regenerate II. Saturated (18-electron) Pt(IV)-hydride complexes obtained by ligand addition or by chelation of the aminoalkyl ligand liberate the product through higher-energy pathways. Other pathways starting from the zwitterionic intermediates were also explored (intermolecular N deprotonation followed by C protonation or chelation to produce platina(II)azacyclobutane derivatives; intramolecular proton transfer from N to C, either direct or assisted by an external aniline molecule) but all gave higher-energy intermediates or led to the same rate-determining TS(XX-L).

Theoretical Study on Mechanism of Cycloadditional Reaction Between Dichloro-Germylidene and Formaldehyde

Mechanism of the cycloadditional reaction between singlet dichloro-germylidene and formaldehyde has been investigated with MP2/6–31G* method, including geometry optimization, vibrational analysis and energies for the involved stationary points on the potential energy surface. Prom the potential energy profile, we predict that the cycloaddition reaction between singlet dichloro-germylidene and formaldehyde has two competitive dominant reaction pathways, going with the formation of two side products (INT3 and INT4), simultaneously. Both of the two competitive reactions consist of two steps, two reactants firstly form a three-membered ring intermediate INT1 and a twisted four-membered ring intermediate INT2, respectively, both of which are barrier-free exothermic reactions of 41.5 and 72.3 kJ/mol; then INT1 isomerizes to a four-membered ring product P1 via transition state TS1, and INT2 isomerizes to a chlorine-transfer product P2 via transition state TS2, with the barriers of 2.9 and 0.3 kJ/mol, respectively. Simultaneously, P1 and INT2 further react with formaldehyde to form INT3 and INT4, respectively, which are also barrier-free exothermic reaction of 74.9 and 88.1 kJ/mol.

Intramolekulare Ringerweiterung eines 2‐Lithium‐anilido‐2‐fluoro‐1,3‐diaza‐2‐silacyclopentens zum 1,3,5‐Triaza‐7‐bora‐2‐silacyclohepten – Experimentelle und Quantenchemische Ergebnisse

AbstractThe reaction between the lithiated 2‐diisopropylanilino‐2‐fluoro‐1,3‐diaza‐2‐silacyclopentene, (HCNCMe3)2SiFNLi(2,6‐Me2CH)2C6H3 (I), and BF3·OEt2 in THF afforded in an unknown, intramolecular ring expansion the seven‐membered 1,3,4‐triaza‐7‐bora‐2‐silacycloheptene, (HCNCMe3)2(SiF2)BFN‐2,6‐(Me2CH)2C6H3 (1). Starting with the BF2‐substituted compound A, quantum‐chemical calculations on the thermal isomeration process revealed a two‐step reaction mechanism: First, the bicyclic compound C is formed via transition state TS1, and second, a 1,3‐fluoride ion migration occurs in the seven‐membered transition state TS2 from a BF2‐ to a SiF‐unit. The reaction mechanism and the structures of the transition states are discussed in detail.

Synthetic studies towards the anti-inflammatory agent, oleocanthal using a Johnson–Claisen (orthoester) rearrangement strategy

The phenol catalysed Johnson orthoester-Claisen rearrangement of allylic alcohol (1R)-6, proceeds via two possible ketene-acetal transition states TS-1 and TS-2, to afford a 1:10 mixture of diastereomers. The transition state configuration of the C-1 methyl group (axial or equatorial) is proposed to be the dominating factor dictating whether the sigmatropic rearrangement takes place from the convex or concave face of the starting material.

Mechanism of the Divanadium-Substituted Polyoxotungstate [γ-1,2-H2SiV2W10O40]4−Catalyzed Olefin Epoxidation by H2O2: A Computational Study

The mechanisms of olefin epoxidation by hydrogen peroxide catalyzed by [gamma-1,2-H(2)SiV(2)W(10)O(40)](4-), 1, were studied using the density functional (B3LYP) approach in conjunction with large basis sets. The role of solvent is taken into account via both including an explicit water molecule into the calculations and using the polarizable continuum model (PCM) with acetonitrile as a solvent (numbers given in parentheses). The countercation effect (using one molecule of Me(4)N(+) as a countercation (1CC)) is also taken into account (numbers given in brackets). It was shown that the formation of the vanadium-hydroperoxo species 2(H(2)O) with an {OV-(mu-OOH)(mu-OH)-VO}(H(2)O) core from 1 and H(2)O(2) is a very facile process. The resulting complex 2(H(2)O) may eliminate a water molecule and form complex 2. From the intermediates 2 and 2(H(2)O), reaction may proceed via two distinct pathways: "hydroperoxo" and "peroxo". The water-assisted "hydroperoxo" pathway starts with coordination of olefin (C(2)H(4)) to 2(H(2)O) and proceeds with a 36.8(25.5)[31.7][(21.6)] kcal/mol rate-determining barrier at the O-atom transfer transition state TS2[TS2(1CC)]. The "water-free peroxo" and "water-assisted peroxo" pathways start with rearrangement of 2 and 2(H(2)O) to vanadium-peroxo species 3 and 3(H(2)O), respectively, with an {OV-(eta(2)-O(2))-VO} core, and follow the O-atom transfer from catalyst to olefin. The 2 --> 3 and 2(H(2)O) --> 3(H(2)O) hydroperoxo --> peroxo rearrangement processes require 16.8(13.0)[13.0][(11.1)] and 14.2(9.0)[1.3][(7.2)] kcal/mol of energy, respectively. The calculated overall energy barriers are 28.1(19.1)[23.8][(17.2)] and 25.4(11.0)[10.6][(13.0)] kcal/mol for "water-free peroxo" and "water-assisted peroxo" pathways, respectively. On the basis of these data we predict that the [gamma-1,2-H(2)SiV(2)W(10)O(40)](4-)-catalyzed olefin epoxidation by H(2)O(2) most likely occurs via a "water-assisted peroxo" pathway.

Nuclear Quantum Tunneling in the Light-activated Enzyme Protochlorophyllide Oxidoreductase

In chlorophyll biosynthesis, the light-activated enzyme protochlorophyllide oxidoreductase catalyzes trans addition of hydrogen across the C-17-C-18 double bond of the chlorophyll precursor protochlorophyllide (Pchlide). This unique light-driven reaction plays a key role in the assembly of the photosynthetic apparatus, but despite its biological importance, the mechanism of light-activated catalysis is unknown. In this study, we show that Pchlide reduction occurs by dynamically coupled nuclear quantum tunneling of a hydride anion followed by a proton on the microsecond time scale in the Pchlide excited and ground states, respectively. We demonstrate the need for fast dynamic searches to form degenerate "tunneling-ready" configurations within the lifetime of the Pchlide excited state from which hydride transfer occurs. Moreover, we have found a breakpoint at -27 degrees C in the temperature dependence of the hydride transfer rate, which suggests that motions/vibrations that are important for promoting light-activated hydride tunneling are quenched below -27 degrees C. We observed no such breakpoint for the proton-tunneling reaction, indicating a reliance on different promoting modes for this reaction in the enzyme-substrate complex. Our studies indicate that the overall photoreduction of Pchlide is endothermic and that rapid dynamic searches are required to form distinct tunneling-ready configurations within the lifetime of the photoexcited state. Consequently, we have established the first important link between photochemical and nuclear quantum tunneling reactions, linked to protein dynamics, in a biologically significant system.

Theoretical study on mechanism of cycloaddition reaction between dimethyl methylene carbene and ethylene

Mechanisms of cycloaddition reaction between singlet dimethyl methylene carbene and ethylene has been investigated with MP2/6-31G ∗ method, including geometry optimization and vibrational analysis. Energies for the involved stationary points on the potential energy surface are corrected by zero-point energy and CCSD(T)//MP2/6-31G ∗ single-point calculations. From the potential energy surface obtained with the CCSD(T)//MP2/6-31G ∗ method for the cycloaddition reaction between singlet dimethyl methylene carbene and ethylene, it can be predicted that reactions (1) and (3) should be two competitive leading channels of cycloaddition reaction between them. The former consists of two steps: (I) the two reactants firstly form an energy-rich intermediate, INT1, which is a barrier-free exothermic reaction; (II) the intermediate INT1 isomerizes to a three-membered ring product P1 via a transition state TS1. The latter proceeds in three steps: (I) the two reactants firstly form a four-membered ring intermediate, INT2, through a barrier-free exothermic reaction; (II) the intermediate INT2 further reacts with ethylene (R2) to form an intermediate, INT3, which is also a barrier-free exothermic reaction; (III) INT3 isomerizes to a polycyclic product P3 via a transition state TS3.

Ab initio study on the mechanism of forming a silapolycyclic compound between methylenesilylene and ethene

The mechanism of the cycloaddition reaction of forming a silapolycyclic compound between singlet methylenesilylene and ethene has been investigated with the MP2/6-31G ∗ method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by the CCSD(T)//MP2/6-31G ∗ method. From the potential energy profile, it can be predicted that, reaction (3) is the dominant channel of cycloaddition reaction between singlet methylenesilylene and ethene. This reaction consists of four steps: (I) the two reactants first form a three-membered ring intermediate INT through a barrier-free exothermic reaction of 13.3 kJ mol −1; (II) INT then isomerizes to a four-membered ring product P2 via the transition state TS2 with an energy barrier of 32.0 kJ mol −1; (III) P2 further reacts with ethene(R2) to form a silapolycyclic intermediate INT3, which is also a barrier-free exothermic reaction of 11.8 kJ mol −1; (IV) INT3 isomerizes to a silapolycyclic compound P3 via the transition state TS3 with an energy barrier of 1.5 kJ mol −1. This reaction has quite excellent selectivity.

Mechanisms of guanosine triphosphate hydrolysis by Ras and Ras‐GAP proteins as rationalized by ab initio QM/MM simulations

The hydrolysis reaction of guanosine triphosphate (GTP) by p21(ras) (Ras) has been modeled by using the ab initio type quantum mechanical-molecular mechanical simulations. Initial geometry configurations have been prompted by atomic coordinates of the crystal structure (PDBID: 1QRA) corresponding to the prehydrolysis state of Ras in complex with GTP. Multiple searches of minimum energy geometry configurations consistent with the hydrogen bond networks have been performed, resulting in a series of stationary points on the potential energy surface for reaction intermediates and transition states. It is shown that the minimum energy reaction path is consistent with an assumption of a two-step mechanism of GTP hydrolysis. At the first stage, a unified action of the nearest residues of Ras and the nearest water molecules results in a substantial spatial separation of the gamma-phosphate group of GTP from the rest of the molecule (GDP). This phase of hydrolysis process proceeds through the low barrier (16.7 kcal/mol) transition state TS1. At the second stage, the inorganic phosphate is formed in consequence of proton transfers mediated by two water molecules and assisted by the Gln61 residue from Ras. The highest transition state at this segment, TS3, is estimated to have an energy 7.5 kcal/mol above the enzyme-substrate complex. The results of simulations are compared to the previous findings for the GTP hydrolysis in the Ras-GAP (p21(ras)-p120(GAP)) protein complex. Conclusions of the modeling lead to a better understanding of the anticatalytic effect of cancer causing mutation of Gln61 from Ras, which has been debated in recent years.

A CASSCF study on photodissociation of the [formula omitted] dianion

N 2 O 3 2 - photodissociation was investigated using the CASSCF energy gradient techniques. After the N 2 O 3 2 - dianion is populated in the S 1 state, the system can undergo different routes. One route involves radiationless decay via an intersystem crossing T 1/S 1 to the T 1 minimum intermediate. Then through the transition state TS (T 1) and the T 1/S 0 to the ground state surface. The other route involves the S 1/S 0 conical intersection. These results show that the main product NO − of the efficient photodissociation is singlet-state rather than triplet ( 3Σ −) state. Our calculated results are in close agreement with experimental observations.

Theoretical Study on the Mechanism of the Cycloaddition Reaction between Methylidenesilene and Ethylene

The mechanism of a cycloaddition reaction between singlet methylidenesilene and ethylene has been investigated with MP2/6-31G∗︁ and B3LYP/6-31G∗︁ methods, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies of the involved conformers were calculated by CCSD(T)//MP2/6-31G∗︁ and CCSD(T)//B3LYP/6-31G∗︁ methods, respectively. The results show that the dominant reaction pathway of the cycloaddition reaction is that a complex intermediate is firstly formed between the two reactants through a barrier-free exothermic reaction of 13.3 kJ/mol, and the complex is then isomerized to a four-membered ring product P2.1 via a transition state TS2.1 with a barrier of 32.0 kJ/mol.

An experimental–theoretical approach to the kinetics and mechanism of Michael type addition: α,β-Unsaturated tungsten Fischer carbene complex as the substrate

Through variable-temperature 1H and 13C NMR experiments and density functional calculations, the kinetics and mechanism of Michael type addition were investigated using alkynyl carbene A as the substrate. The two conformers of substrate A were distinguished from the 1H and 13C NMR spectra, and the calculated results showed that the syn-conformer is more stable than the anti- by 6.5 kJ mol −1 with the activation barrier between these two conformers as 62.5 kJ mol −1. The full reaction mechanism of Michael type addition was first presented to us, which differs from the previous solely based on the kinetic studies. It contains three elementary steps (see the scheme): (1) Formation of C 8–N 2 bond via transition state TS 1. (2) Conformation conversion from In 1 to In 2, which is very important but ignored before. (3) Intramolecular proton transfer via transition state TS 2 forming the product. The first step is rate determining with an activation barrier of 73.0 kJ mol −1, very close to the experimental value of 89.6 kJ mol −1. The product P is dominant over P′ in population contrary to the situation of tautomer B′ over B, which is caused by larger activation barriers to P′ and the less stabilities of structures related to B′ from the first transition state to the product. [Display omitted]

Ketene−Ketenimine Rearrangements in the Gas Phase and in Polar Media. 1,3-Migration Intermediates and Sequential Transition States

[reaction: see text] Calculations of the activation barrier for the 1,3-shifts of substituents X in alpha-imidoylketenes 1 (HN=C(X)-CH=C=O), which interconverts them with alpha-oxoketenimines 3 (HN=C=CH-C(X)=O) via a four-membered cyclic transition state TS2 have been performed at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G* level. Substituents with accessible lone pairs have the lowest activation barriers for the 1,3-shift (halogens, OR, NR2). The corresponding activation barriers for the alpha-oxoketene-alpha-oxoketene rearrangement of 4 via TS5 are generally lower by 1-30 kJ/mol. A polar medium (acetonitrile, epsilon = 36.64) was simulated using the polarizable continuum (PCM) solvation model. The effect of the solvent field is a reduction of the activation barrier by an average of 12 kJ/mol. In the cases of 1,3-shifts of amino and dimethylamino groups, the stabilization of the transition state TS2 in a solvent field is so large that it becomes an intermediate, Int2, flanked by transition states (TS2' and TS2'') that are due primarily to internal rotation of the amine functions, and secondarily to the 1,3-bonding interaction. In the case of the alpha-oxoketene-alpha-oxoketene rearrangement of 4, there is a corresponding intermediate Int5 for the 1,3-amine shift already in the gas phase.

Theoretical Study on the Mechanism of the Cycloaddition Reaction between Dichloromethylene Germylene and Ethylene

AbstractThe mechanism of a cycloaddition reaction between singlet dichloromethylene germylene and ethylene has been investigated with B3LYP/6‐31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies for the involved conformations were calculated by CCSD(T)//B3LYP/6‐31G* method. On the basis of the surface energy profile obtained with CCSD(T)// B3LYP/6‐31G* method for the cycloaddition reaction between singlet dichloromethylene germylene and ethylene, it can be predicted that the dominant reaction pathway is that an intermediate INT1 is firstly formed between the two reactants through a barrier‐free exothermic reaction of 61.7 kJ/mol, and the intermediate INT1 then isomerizes to an active four‐membered ring product P2.1 via a transition state TS2, an intermediate INT2 and a transition state TS2.1 , in which energy barriers are 57.7 and 42.2 kJ/mol, respectively.

Ab Initio Study on the Mechanism of Forming a Germanic Hetero-Polycyclic Compound between Alkylidenegermylene and Ethylene

The mechanism of the cycloaddition reaction of forming a germanic hetero-polycyclic compound between singlet alkylidenegermylene and ethylene has been investigated with MP2/6-31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by CCSD(T)//MP2/6-31G* method. From the surface energy profile, it can be predicted that the dominant reaction pathway for this reaction consists of three steps: the two reactants first form a three-membered ring intermediate INT1 through a barrier-free exothermic reaction of 35.4 kJ/mol; this intermediate then isomerizes to an active four-membered ring product P2.1 via a transition-state TS2.1 with a barrier of 57.6 kJ/mol; finally, P2.1 further reacts with ethylene to form the germanic hetero-polycyclic compound P3, for which the barrier is only 0.8 kJ/mol. The rate of this reaction path considerably differs from other competitive reaction paths, indicating that the cycloaddition reaction has an excellent selectivity.

Conformational detours during folding of a collapsed state

The protein S6 is a useful model to probe the role of partially folded states in the folding process. In the absence of salt, S6 folds from the denatured state D to the native state N without detectable intermediates. High concentrations of sodium sulfate induce the accumulation of a collapsed state C, which is off the direct folding route. However, the mutation VA85 enables S6 to fold from C directly to N through the transition state TS C. According to the denaturant dependence of this reaction, TS C and C are equally compact, but the data are difficult to deconvolute. Therefore, I have measured the heat capacities (Δ C p) for the D→C and C→TS C transitions. The Δ C p-values suggest that C needs to increase its surface area in order to fold directly to N. This underlines that it is a misfolded state that can only fold by at least partial unfolding. In contrast to the C-state formed by S6 wildtype, the VA85 C-state is just as compact as the native state, and this may be a prerequisite for direct folding. Individual “gatekeeper” residues may thus play a disproportionately large role in guiding proteins through different folding pathways.

QM/MM modeling the Ras–GAP catalyzed hydrolysis of guanosine triphosphate

The mechanism of the hydrolysis reaction of guanosine triphosphate (GTP) by the protein complex Ras-GAP (p21(ras) - p120(GAP)) has been modeled by the quantum mechanical-molecular mechanical (QM/MM) and ab initio quantum calculations. Initial geometry configurations have been prompted by atomic coordinates of a structural analog (PDBID:1WQ1). It is shown that the minimum energy reaction path is consistent with an assumption of two-step chemical transformations. At the first stage, a unified motion of Arg789 of GAP, Gln61, Thr35 of Ras, and the lytic water molecule results in a substantial spatial separation of the gamma-phosphate group of GTP from the rest of the molecule (GDP). This phase of hydrolysis process proceeds through the low-barrier transition state TS1. At the second stage, Gln61 abstracts and releases protons within the subsystem including Gln61, the lytic water molecule and the gamma-phosphate group of GTP through the corresponding transition state TS2. Direct quantum calculations show that, in this particular environment, the reaction GTP + H(2)O --> GDP + H(2)PO(4) (-) can proceed with reasonable activation barriers of less than 15 kcal/mol at every stage. This conclusion leads to a better understanding of the anticatalytic effect of cancer-causing mutations of Ras, which has been debated in recent years.

A Theoretical Study on the Mechanism of the Cycloaddition Reaction between Alkylidenestannylene and Ethylene

The mechanism of a cycloaddition reaction between singlet alkylidenestannylene and ethylene has been investigated with MP2/3-21G* and B3LYP/3-21G* methods, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies for the involved conformations were calculated by CCSD(T)//MP2/3-21G* and CCSD(T)//B3LYP/3-21G* methods, respectively. The results show that the dominant reaction pathway of the cycloaddition is that an intermediate (INT) is firstly formed between the two reactants through a barrier-free exothermic reaction of 39.7 kJ/mol, and the intermediate then isomerizes to a four-membered ring product (P2.1) via a transition state TS2.1 with a barrier of 66.8 kJ/mol.

Theoretical study on the dehydrogenation reaction of H 2S by ScS + ( 1Σ +)

Abastract The dehydrogenation reaction of H2S by the 1Σ+ ground state of ScS+:ScS++H2S→ScS2++H2 in the gas phase has been studied by using density functional theory (DFT) at B3LYP/DZVP level. It is found that the reaction has a two-step-reaction mechanism which involved two H atoms shift reactions from S1 to Sc+ via the transition state TS1 and TS2, respectively. The reaction proceeds via TS1 for the migration of the first hydrogen is the rate-determining step and the activation energy is 34.1 kcal/mol at B3LYP/DZVP level relative to the reactants. The calculated reaction heat is −8.7 kcal/mol and indicates the exothermicity of the reaction.