Evaluation of Influencing Factors in Tetravalent Uranium Complex-Mediated CO2 Functionalization by Density Functional Theory.

The functionalization of CO2 mediated by a series of U(IV) mixed-sandwich compounds, (COTTIPS2)Cp*UR (R = -CH3, -CH2Ph, -CH2TMS, -CH(TMS)2, -NHPh, -OPh, -SPh, -SePh; COTTIPS2 = C8H6(SiiPr3-1,4)2; Cp* = C5Me5; TMS = SiMe3), was investigated by the density functional theory method. A two-step mechanism was revealed, in which the insertion of CO2 into the U-C bond was identified as the rate-determining step via a transition state featured by a four-membered ring with a free-energy barrier of 18.8 kcal/mol to the reaction of the (COTTIPS2)Cp*UCH3 system. The whole reaction was strongly exothermic by 45.0 kcal/mol. Substitution effect was discussed, including the bulkiness of the R group and the nature of the ligating atom, and steric hindrance and electrostatic interactions were found to be responsible for the observed variation in reactivity. The reactivity of U(III) and U(IV) complexes in CO2 functionalization was also compared and discussed. The results were consistent with experimental studies and complemented with molecular level of understanding on the mechanisms of CO2 functionalization promoted by tetravalent U complexes.

Theoretical investigation of the first-shell mechanism of acetylene hydration catalyzed by a biomimetic tungsten complex.

The reaction mechanism of the hydration of acetylene to acetaldehyde catalyzed by [W(IV)O(mnt)(2)](2-) (where mnt(2-) is 1,2-dicyanoethylenedithiolate) is studied using density functional theory. Both the uncatalyzed and the catalyzed reaction are considered to find out the origin of the catalysis. Three different models are investigated, in which an aquo, a hydroxo, or an oxo coordinates to the tungsten center. A first-shell mechanism is suggested, similarly to recent calculations on tungsten-dependent acetylene hydratase. The acetylene substrate first coordinates to the tungsten center in an η(2) fashion. Then, the tungsten-bound hydroxide activates a water molecule to perform a nucleophilic attack on the acetylene, resulting in the formation of a vinyl anion and a tungsten-bound water molecule. This is followed by proton transfer from the tungsten-bound water molecule to the newly formed vinyl anion intermediate. Tungsten is directly involved in the reaction by binding and activating acetylene and providing electrostatic stabilization to the transition states and intermediates. Three other mechanisms are also considered, but the associated energetic barriers were found to be very high, ruling out those possibilities.

Why iron? A spin-polarized conceptual density functional theory study on metal-binding specificity of porphyrin.

Heme is a key cofactor of hemoproteins in which porphyrin is often found to be preferentially metalated by the iron cation. In our previous work [Feng, X. T.; Yu, J. G.; Lei, M.; Fang, W. H.; Liu, S. B. J. Phys. Chem. B 2009, 113, 13381], conceptual density functional theory (CDFT) descriptors have been applied to understand the metal-binding specificity of porphyrin. We found that the iron-porphyrin complex significantly differs in many aspects from porphyrin complexes with other metal cations except Ru, for which similar behaviors for the reactivity descriptors were discovered. In this study, we employ the spin-polarized version of CDFT to investigate the reactivity for a series of (pyridine)(n)-M(ll)-porphyrin complexes-where M = Mg, Ca, Cr, Mn, Co, Ni, Cu, Zn, Ru, and Cd, and n = 0, 1, and 2-to further appreciate the metal-binding specificity of porphyrin. Both global and local descriptors were examined within this framework. We found that, within the spin resolution, not only chemical reactivity descriptors from CDFT of the iron complex are markedly different from that of other metal complexes, but we also discovered substantial differences in reactivity descriptors between Fe and Ru complexes. These results confirm that spin properties play a highly important role in physiological functions of hemoproteins. Quantitative reactivity relationships have been revealed between global and local spin-polarized reactivity descriptors. These results contribute to our better understanding of the metal binding specificity and reactivity for heme-containing enzymes and other metalloproteins alike.

DFT study of the asymmetric nitroaldol (Henry) reaction catalyzed by a dinuclear Zn complex.

We report the mechanism of asymmetric nitroaldol (Henry) reaction catalyzed by a dinuclear Zn complex using density functional theory. The experimentally proposed catalytic cycle is validated, in which the first step is the deprotonation of nitromethane by the ethyl anion of the catalyst, subsequently a C-C bond formation step, and then the protonation of the resulting alkoxide. Three mechanistic scenarios (differing in binding modes) have been considered for the C-C bond formation step. The origin of the enantioselectivity is discussed. Our calculations supported that the S configurations are the major products, which is in agreement with the experimental observations.

Dipeptide hydrolysis by the dinuclear zinc enzyme human renal dipeptidase: mechanistic insights from DFT calculations.

The reaction mechanism of the dinuclear zinc enzyme human renal dipeptidase is investigated using hybrid density functional theory. This enzyme catalyzes the hydrolysis of dipeptides and beta-lactam antibiotics. Two different protonation states in which the important active site residue Asp288 is either neutral or ionized were considered. In both cases, the bridging hydroxide is shown to be capable of performing the nucleophilic attack on the substrate carbonyl carbon from its bridging position, resulting in the formation of a tetrahedral intermediate. This step is followed by protonation of the dipeptide nitrogen, coupled with C-N bond cleavage. The calculations establish that both cases have quite feasible energy barriers. When the Asp288 is neutral, the hydrolytic reaction occurs with a large exothermicity. However, the reaction becomes very close to thermoneutral with an ionized Asp288. The two zinc ions are shown to play different roles in the reaction. Zn1 binds the amino group of the substrate, and Zn2 interacts with the carboxylate group of the substrate, helping in orienting it for the nucleophilic attack. In addition, Zn2 stabilizes the oxyanion of the tetrahedral intermediate, thereby facilitating the nucleophilic attack.

DFT study on the mechanism of Escherichia coli inorganic pyrophosphatase.

Escherichia coli inorganic pyrophosphatase (E-PPase) is a tetranuclear divalent metal dependent enzyme that catalyzes the reversible interconversion of pyrophosphate (PPi) and orthophosphate (Pi), with Mg(2+) conferring the highest activity. In the present work, the reaction mechanism of E-PPase is investigated using the hybrid density functional theory (DFT) method B3LYP with a large model of the active site. Our calculated results shed further light on the detailed reaction mechanism. In particular, the important residue Asp67, either protonated or unprotonated, was taken into account in the present calculations. Our calculations indicated that a protonated Asp67 is crucial for the reverse reaction to take place; however, it is lost sight of in the forward reaction. The bridging hydroxide is shown to be capable of performing nucleophilic in-line attack on the substrate from its bridging position in the presence of four Mg(2+) ions. During the catalysis, the roles of the four magnesium ions are suggested to provide a necessary conformation of the active site, facilitate the nucleophile formation and substrate orientation, and stabilize the trigonal bipyramid transition state, thereby lowering the barrier for the nucleophilic attack.

Octacoordinate carbons encaged inside carborane clusters: a density functional theory investigation.

This work focuses on the computational design and characterization of a novel series of endohedral carborane clusters containing octacoordinate carbon centers. The structural and bonding features and the thermodynamic and kinetic stabilities are discussed extensively based on density functional theory calculations. These nonclassical carboranes are fascinating in structure not only for the octacoordinate carbon center but also for the surrounding carbon and boron ligands with inverted bonding configuration. These endohedral carboranes are higher in energy than the corresponding exohedral isomers due to the high strain in the system. A new stability rule based on the donor-acceptor model is proposed to predict the stability ordering for these carborane isomers. In addition, some of these octacoordinate carboranes might have relatively high kinetic stabilities, which is rather hopeful for the experimental syntheses.

Theoretical studies on pyridoxal 5'-phosphate-dependent transamination of alpha-amino acids.

Density functional methods have been applied to investigate the irreversible transamination between glyoxylic acid and pyridoxamine analog and the catalytic mechanism for the critical [1,3] proton transfer step in aspartate aminotransferase (AATase). The results indicate that the catalytic effect of pyridoxal 5'-phosphate (PLP) may be attributed to its ability to stabilize related transition states through structural resonance. Additionally, the PLP hydroxyl group and the carboxylic group of the amino acid can shuttle proton, thereby lowering the barrier. The rate-limiting step is the tautomeric conversion of the aldimine to ketimine by [1,3] proton transfer, with a barrier of 36.3 kcal/mol in water solvent. A quantum chemical model consisting 142 atoms was constructed based on the crystal structure of the native AATase complex with the product L-glutamate. The electron-withdrawing stabilization by various residues, involving Arg386, Tyr225, Asp222, Asn194, and peptide backbone, enhances the carbon acidity of 4'-C of PLP and Calpha of amino acid. The calculations support the proposed proton transfer mechanism in which Lys258 acts as a base to shuttle a proton from the 4'-C of PLP to Calpha of amino acid. The first step (proton transfer from 4'-C to lysine) is shown to be the rate-limiting step. Furthermore, we provided an explanation for the reversibility and specificity of the transamination in AATase.

Water-assisted transamination of glycine and formaldehyde.

A computational study on the transamination reaction of molecular complexes that consist of NH2CH2COOH + CH2O + nH2O, where n = 0, 1, 2, is presented. This work has allowed the description of the geometries of all the intermediates and transition states of the reactions, which can be described by five steps: carbinolamine formation, dehydration, 1,3 proton transfer, hydrolysis, and carbinolamine elimination. Among the five steps of the reaction, hydrolysis and elimination occur with the existence of general acid catalysis related to the carboxylic group. The water molecules can be involved in the reaction by performing as a proton-transfer carrier and a stabilizing zwitterion. It can be predicted from our calculations that in the transamination between alpha-amino acids and alpha-keto acids, the carbinolamine is formed with small barrier or even barrierless while the dehydration occurs easily at room temperature. However, without heating the 1,3 proton transfer could not occur as the barrier is 26.7 kcal/mol relative to the reactant complex when including two water molecules. Our results are in good agreement with experimental conclusions.

Insights into the photochemical processes of ClC(O)SCl from ab initio calculations.

All possible unimolecular processes upon photolysis of ClC(O)SCl in the UV-visible region have been characterized in the present paper through the optimized stationary structures and computed potential-energy profiles of the S0, S1, T2, and S2 states with the MP2, B3LYP, CASSCF, and MR-CI methods in conjugation with the cc-pVDZ basis set. Upon photoexcitation in the range of 300-400 nm, the ClC(O)SCl molecules are excited to the S1 state. From this state, the dissociation into ClC(O)S + Cl takes place immediately and subsequently Cl2 and SCO are formed. The C-Cl and C-S bond fissions that start from the S2 state are the dominant channels upon photodecomposition of ClC(O)SCl in the gas and condensed phases in the wavelength range of 200-248 nm. The formed Cl, C(O)SCl, ClCO, and SCl radicals are very reactive, and the Cl2, SCO, CO, and SCl2 molecules are subsequently produced as stable products in the condensed phase.

Hexa- and octacoordinate carbon in hydrocarbon cages: theoretical design and characterization.

A new series of hydrocarbon cages containing hexa- and octacoordinate carbon centers were designed theoretically by performing DFT calculations at the B3 LYP/6-311+G** level. Among these non-classical structures that were found to still obey the 8e rule, the two tetracations with octacoordinate carbons may be the first examples found in pure hydrocarbons. Structural characteristics, as well as thermodynamic and kinetic stabilities, were also investigated theoretically for these two octacoordinate tetracations. These hydrocarbon compounds containing hypercoordinate carbon centers provide a challenge for synthetic organic chemists.

Systematic size study of an insect antifreeze protein and its interaction with ice.

Because of their remarkable ability to depress the freezing point of aqueous solutions, antifreeze proteins (AFPs) play a critical role in helping many organisms survive subzero temperatures. The beta-helical insect AFP structures solved to date, consisting of multiple repeating circular loops or coils, are perhaps the most regular protein structures discovered thus far. Taking an exceptional advantage of the unusually high structural regularity of insect AFPs, we have employed both semiempirical and quantum mechanics computational approaches to systematically investigate the relationship between the number of AFP coils and the AFP-ice interaction energy, an indicator of antifreeze activity. We generated a series of AFP models with varying numbers of 12-residue coils (sequence TCTxSxxCxxAx) and calculated their interaction energies with ice. Using several independent computational methods, we found that the AFP-ice interaction energy increased as the number of coils increased, until an upper bound was reached. The increase of interaction energy was significant for each of the first five coils, and there was a clear synergism that gradually diminished and even decreased with further increase of the number of coils. Our results are in excellent agreement with the recently reported experimental observations.

Striving to understand the photophysics and photochemistry of thiophosgene: a combined CASSCF and MR-CI study.

The potential energy surfaces for Cl(2)CS dissociation into ClCS + Cl in the five lowest electronic states have been determined with the combined complete active space self-consistent field (CASSCF) and MR-CI method. The wavelength-dependent photodissociation dynamics of Cl(2)CS have been characterized through computed potential energy surfaces, surface crossing points, and CASSCF molecular dynamics calculations. Irradiation of the Cl(2)CS molecules at 360-450 nm does not provide sufficient internal energy to overcome the barrier on S(1) dissociation, and the S(1)/T(2) intersection region is energetically inaccessible at this wavelength region; therefore, S(1) --> T(1) intersystem crossing is the dominant process, which is the main reason S(1)-S(0) fluorescence breaks off at excess energies of 3484-9284 cm(-1). Also, the S(1) --> T(2) intersystem crossing process can take place via the S(1)-T(2) vibronic interaction in this range of excess energies, which is mainly responsible for the quantum beats observed in the S(1) emission. Both S(2) direct dissociation and S(2) --> S(3) internal conversion are responsible for the abrupt breakoff of S(2)-S(0) fluorescence at higher excess energies. S(2) direct dissociation leads to the formation of the fragments of Cl(X(2)P) + ClCS(A(2)A' ') in excited electronic states, while S(2) --> S(3) internal conversion followed by direct internal conversion to the ground electronic state results in the fragments produced in the ground state.

The role of charge transfer in the hydrogen bond cooperative effect of cis-N-methylformamide oligomers.

Two accumulating molecular systems have been designed to investigate the cooperative effect of hydrogen bonding in theory. The first system included a series of linear oligomers of cis-N-methylformamide (c-NMF) molecules. Substantial cooperative effect has been confirmed in the electronic structures and energies of the hydrogen bonds in them as shown by the results obtained using the B3LYP method at the level of cc-pVTZ basis sets. Such a cooperative effect gradually increases with the growth of the c-NMF oligomer. The second system included a series of modified c-NMF trimers whose central c-NMF molecules contained insertion fragments of varying structural and electrical compositions. On the basis of an examination of the structures and charge populations of the c-NMF oligomers in these two systems, a mechanism of the cooperative effect of hydrogen bonding in these systems based on charge flow in the c-NMF molecules is proposed. The results from the second system of c-NMF trimers were particularly instrumental in formulating this mechanism, because the charge flows between the C=O and N-H groups in the modified c-NMF molecule of these trimers were dampened by the various molecular insertions. A clear correlation between the degree of charge flow dampening from each inserted fragment and the magnitude of the cooperative effect of hydrogen bonding was observed. On the basis of an analysis of the electronic structural characteristics of the molecular fragments, we conclude that the charge flow between the hydrogen bond donor and acceptor groups in the c-NMF molecule is the most important factor inducing the cooperative effect of hydrogen bonding.

Computational study on the function of water within a beta-helix antifreeze protein dimer and in the process of ice-protein binding.

Antifreeze proteins (AFPs) help many organisms protect themselves from freezing in subzero temperatures. The most active AFPs found to date are those from insects, which possess exceptionally regular beta-helical structures. On the ice-binding surface of these proteins, regularly arrayed water molecules are observed within the repeating Thr-Xxx-Thr motif, but the exact role of these water molecules remains unknown. In this work, we have employed a number of computational methods to examine the role of these water molecules in an AFP from Tenebrio molitor (TmAFP). Our investigation involved a combination of molecular and quantum mechanical approaches. Properties such as stability, interaction energy, orbital overlap, and conformational analysis of various systems, including TmAFP-water, TmAFP-water-ice, and TmAFP-ice, were systematically evaluated and compared. The regularly arrayed water molecules were found to remain associated with TmAFP before ice binding, demonstrating that they are an intrinsic part of the protein. These water molecules may assist TmAFP in the process of ice recognition and binding. However, after facilitating the initial stages of ice recognition and binding, these water molecules are excluded in the final formation of the AFP-ice complex. The departure of these water molecules enables a better two-dimensional match between TmAFP and ice. These results agree with experimental observations showing that although these water molecules are aligned with the ice-binding hydroxyl groups of Thr residues in one dimension, they are in fact positioned slightly off in the second dimension, making a good two-dimensional match impossible.

Photodissociation of acetic acid in the gas phase: an ab initio study.

Photodissociation of acetic acid in the gas phase was investigated using ab initio molecular orbital methods. The stationary structures on the ground-state potential energy surfaces were mainly optimized at the MP2 level of theory, while those on the excited-state surfaces were determined by complete active space SCF calculations with a correlation-consistent basis set of cc-pVDZ. The reaction pathways leading to different photoproducts are characterized on the basis of the computed potential energy surfaces and surface crossing points. The calculations reproduce the experimental results well and provide additional insight into the mechanism of the ultraviolet photodissociation of acetic acid and related compounds.

Theoretical studies on cycloaddition reactions between 1-aza-2-azoniaallene cation and olefins.

Density functional (B3LYP) calculations using the 6-31++g basis set have been employed to study the title reaction between the cationic 1,3-dipolar 1-aza-2-azoniaallene ion (H2C=N(+)=NH) and ethene. Our calculations confirmed that [3 + 2] cycloaddition reaction takes place via a three-membered ring intermediate. In addition, solvent effects and substituent effects were also studied. For the reactions involving tetrachloroethene, there are two attacking sites. One is on the NH group in the 1-aza-2-azoniaallene ion, another is on its terminal CH2 group, and they are competitive for both approaching positions. Electron-releasing methyl substituents on ethene favor the reaction, and the potential energy surface is quite different from the previous one.

Analysis of ice-binding sites in fish type II antifreeze protein by quantum mechanics.

Many organisms living in cold environments can survive subzero temperatures by producing antifreeze proteins (AFPs) or antifreeze glycoproteins. In this paper we investigate the ice-binding surface of type II AFP by quantum mechanical methods, which, to the best of our knowledge, represents the first time that molecular orbital computational approaches have been applied to AFPs. Molecular mechanical approaches, including molecular docking, energy minimization, and molecular dynamics simulation, were used to obtain optimal systems for subsequent quantum mechanical analysis. We selected 17 surface patches covering the entire surface of the type II AFP and evaluated the interaction energy between each of these patches and two different ice planes using semi-empirical quantum mechanical methods. We have demonstrated the weak orbital overlay phenomenon and the change of bond orders in ice. These results consistently indicate that a surface patch containing 19 residues (K37, L38, Y20, E22, Y21, I19, L57, T56, F53, M127, T128, F129, R17, C7, N6, P5, G10, Q1, and W11) is the most favorable ice-binding site for both a regular ice plane and an ice plane where water O atoms are randomly positioned. Furthermore, for the first time the computation results provide new insights into the weakening of the ice lattice upon AFP binding, which may well be a primary factor leading to AFP-induced ice growth inhibition.