Ramon Crehuet

The Ozonolysis of Ethylene: A Theoretical Study of the Gas‐Phase Reaction Mechanism

An important source of atmospheric polution, the gas-phase ozonolysis of ethylene, has been submitted to systematic theoretical investigation. Apart from its concerted cleavage to the Criegee intermediates, the ethylene primary ozonide (POZ) decomposes in a stepwise mechanism by the alternative routes shown here.

Tropospheric formation of hydroxymethyl hydroperoxide, formic acid, H2O2, and OH from carbonyl oxide in the presence of water vapor: a theoretical study of the reaction mechanism.

We have carried out a theoretical investigation of the gas-phase reaction mechanism of the H2COO+ H2O reaction, which is interesting for atmospheric purposes. The B3LYP method with the 6-31G(d,p) and 6-311 + G(2d,2p) basis sets was employed for the geometry optimization of the stationary points. Additionally, single-point CCSD(T)/6-311 + G(2d,2p) energy calculations have been done for the B3LYP/6-311 + G(2d,2p) optimized structures. The reaction begins with the formation of a hydrogen-bond complex that we have calculated to be 6 kcalmol(-1) more stable than the reactants. Then, the reaction follows two different channels. The first one leads to the formation of hydroxymethyl hydroperoxide (HMHP), for which we have calculated an activation barrier of deltaGa(298) = 11.3 kcalmol(-1), while the second one gives HCO + OH + H2O, with a calculated activation barrier of deltaGa(298) = 20.9 kcalmol(-1). This process corresponds to the water-catalyzed decomposition of H2COO, and its unimolecular decomposition has been previously reported in the literature. Additionally, we have also investigated the HMHP decomposition. We have found two reaction modes that yield HCOOH+H2O; one reaction mode leads to H2CO + H2O2 and a homolytic cleavage, which produces H2COOH + OH radicals. Furthermore, we have also investigated the water-assisted HMHP decomposition, which produces a catalytic effect of about 14 kcalmol(-1) in the process that leads to H2CO + H2O2.

The reaction path intrinsic reaction coordinate method and the Hamilton-Jacobi theory

The definition and location of an intrinsic reaction coordinate path is of crucial importance in many areas of theoretical chemistry. Differential equations used to define the path hitherto are complemented in this study with a variational principle of Fermat type, as Fukui [Int. J. Quantum Chem., Quantum Chem. Symp. 15, 633 (1981)] reported in a more general form some time ago. This definition is more suitable for problems where initial and final points are given. The variational definition can naturally be recast into a Hamilton-Jacobi equation. The character of the variational solution is studied via the Weierstrass necessary and sufficient conditions. The characterization of the local minima character of the intrinsic reaction coordinate is proved. Such result leads to a numerical algorithm to find intrinsic reaction coordinate paths based on the successive minimizations of the Weierstrass E-function evaluated on a guess curve connecting the initial and final points of the desired path.

Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members.

Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities.

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm.

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function.

Neutral Gold(I) Metallosupramolecular Compounds: Synthesis and Characterization, Photophysical Properties, and Density Functional Theory Studies

The reaction of the tris-indole InTREN ligand (L) with different gold phosphine fragments allows the construction of new gold(I) complexes with different geometries depending on the chosen phosphine. A metallodendrimeric structure is obtained when the gold atom is linked to a triphenylphosphine ligand, and neutral gold(I) metallocryptands are constructed when a triphosphine is used. Characterization of the compounds was accomplished by 31P{1H} and 1H NMR, IR, absorption, and fluorescence spectroscopies, electrospray ionization mass spectrometry (ESI-MS(+)), and elemental analysis, and their geometry was optimized using density functional theory (B3LYP). Time-dependent density functional theory (TD-DFT) calculations have been used to assign the lowest energy absorption bands to LMCT N(p, tertiary amine)-->Au transitions. Photophysical characterization of the complexes shows strong luminescence in the solid state. The formation of heterobimetallic species has been detected in solution in the presence of equimolar quantities of metal cations, and their structures have been identified by a combination of spectroscopic methods and mass spectrometry.

Inductive and External Electric Field Effects in Pentacoordinated Phosphorus Compounds.

Pentacoordination at phosphorus is associated with a nucleophilic displacement reaction at tetracoordinated phosphorus compounds and shows a great variability in what respects their geometrical and energetic features. By means of a systematic theoretical study on a series of elementary model compounds, we have analyzed the bonding features. The pentacoordinated phosphorus compounds are held together by dative bonds, and the geometry and stability depends on the inductive effects originated by different substitutes at phosphorus. We show also that an external electric field can modify the geometrical features and the reactivity of the nucleophilic substitution reactions. This issue may have great interest in biological reactions involving pentacoordinated phosphorus where the electric field originated by the folded protein could influence the catalytic process. We report also additional calculations on the geometry and NMR spectra on three triphenyl phosphonium ylide derivatives, and our results compare well with the experimental data.

Prediction of approximate transition states by Bell–Evans–Polanyi principle: I

We propose a specific mathematical model of the Bell–Evans–Polanyi principle (BEP) to locate approximate transition structures of elementary reactions. The BEP adiabatic energy surface is built as a combination of three quadratic energy surfaces. Two of these quadratic energy surfaces are associated with the reactants and products, whereas the third one is associated with the crossing point energy minimum resulting from the intersection of the reactant and product quadratic energy surfaces. In this way, the resonance energy terms are taken into account. The resulting approximate transition structure and the corresponding Hessian matrix can be used as an initial geometry and a Hessian matrix to locate and optimize the true transition state on the real potential energy surface. In addition, the method provides a simple way to analyze the transition in terms of the contribution weights of the reactants and products. This model is illustrated by different numerical examples, such as the analytical Müller–Brown potential energy surface, the ring opening of cyclopropyl radical, the rearrangement of trans‐hydroxycarbene to formaldehyde, and the rearrangement of bicyclo[3.1.0]hex‐3‐en‐2‐il radical to cyclohexadienyl radical. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1112–1129, 1999

Protein Flexibility and Metal Coordination Changes in DHAP‐Dependent Aldolases

The mobility of rhamnulose-1-phosphate aldolase (RhuA) was analysed with a normal mode description and high level calculations on models of the active site. We report the connection between the mobility and the chemical properties of the active site, and compare them to a closely related enzyme, fuculose-1-phosphate aldolase (FucA). Calculations show that the different coordination number for the zinc ion, reported in the crystal structures of RhuA and FucA, was due to a different spatial arrangement of the residues, not to their different chemical nature. Moreover, the metal coordination change is correlated with activity. The domain mobility of the enzyme can reshape the active site of RhuA into the arrangement found in the FucA structure, and vice-versa. This has a direct influence on the energy barrier for the aldol reaction catalyzed by these enzymes, thus showing a coupling of the domain movements and the catalytic effects. Hence domain movements and the coordination chemistry of the active site metal suggest an explanation of why these enzymes have similar experimental turnover rates.

Pentacoordinated phosphorus revisited by high‐level QM/MM calculations

Enzymes catalyzing phosphoryl transfer reactions are extremely efficient and are involved in crucial biochemical processes. The mechanisms of these enzymes are complex due to the diversity of substrates that are involved. The reaction can proceed through a pentacoordinated phosphorus species that is either a stable intermediate or a transition state (TS). Because of this, the first X‐ray structure of a pentacoordinated phosphorus intermediate in the β‐phosphoglucomutase enzyme aroused great interest but also much controversy. To provide new insights into the nature of that structure, we have determined the reaction path of the phosphorylation step using high‐level QM/MM calculations, and have also calculated the geometry of a complex with a transition state analogue (TSA) that has been suggested to be the actual species in the crystal. The protein crystalline environment has been modeled so as to mimic the experimental conditions. We conclude that the pentacoordinated phosphorus formed in this enzyme is not a stable species but a TS, which gives an activation energy for phosphorylation in agreement with kinetic results. We also show that the TSA is a good mimic of the true TS. We have performed a new crystallographic refinement of the original diffraction map of the pentacoordinated phosphorus structure with the MgF  3− TSA. The new fit improves significantly with respect to the original one, which strongly supports that Allen and coworkers wrongly assigned the X‐ray structure to a pentavalent phosphorane. Proteins 2010.