Complete Energy Profile Research Articles

A QM/MM study on the catalytic mechanism of pyruvate decarboxylase

Pyruvate decarboxylase (PDC) is a typical thiamin diphosphate (ThDP)-dependent enzyme with widespread applications in industry. Though studies regarding the reaction mechanism of PDC have been reported, they are mainly focused on the formation of ThDP ylide and some elementary steps in the catalytic cycle, studies about the whole catalytic cycle of PDC are still not completed. In these previous studies, a major controversy is whether the key active residues (Glu473, Glu50′, Asp27′, His113′, His114′) are protonated or ionized during the reaction. To explore the catalytic mechanism and the role of key residues in the active site, three whole-enzyme models were considered, and the combined QM/MM calculations on the nonoxidative decarboxylation of pyruvate to acetaldehyde catalyzed by PDC were performed. According to our computational results, the fundamental reaction pathways, the complete energy profiles of the whole catalytic cycle, and the specific role of key residues in the common steps were obtained. It is also found that the same residue with different protonation states will lead to different reaction pathways and energy profiles. The mechanism derived from the model in which the residues (Glu473, Glu50′, Asp27′, His113′, His114′) are in their protonated states is most consistent with experimental observations. Therefore, extreme care must be taken when assigning the protonation states in the mechanism study. Because the experimental determination of protonation state is currently difficult, the combined QM/MM method provides an indirect means for determining the active-site protonation state.

Origin of the Increase of Activity and Selectivity of Nickel Doped by Au, Ag, and Cu for Acetylene Hydrogenation

Activity and selectivity are both important issues in heterogeneous catalysis and recent experimental results have shown that Ni catalysts doped by gold exhibit high activity for the hydrogenation of acetylene with good selectivity of ethylene formation. To unravel the underlying mechanism for this observation, the general trend of activity and selectivity of Ni surfaces doped by Au, Ag, and Cu has been investigated using density functional theory calculations. Complete energy profiles from C2H2 to C2H4 on Ni(111), Au/Ni(111), Ag/Ni(111) and Cu/Ni(111) are obtained and their turnover frequencies (TOFs) are computed. The results show that acetylene adsorption on Ni catalyst is strong which leads to the low activity while the doping of Au, Ag, and Cu on the Ni catalyst weakens the acetylene adsorption, giving rise to the increase of activity. The selectivity of ethylene formation is also quantified by using the energy difference between the hydrogenation barriers and the absolute value of the adsorption ene...

RRKM modeling of collision activated reaction/collision induced dissociation experiments: Energy profile determination for phenylethyne incorporation on palladium (II)–phosphinous acid complex

We have recently reported a detailed ESI-collision activated reaction/collision activated reaction (ESI-CAR/CAR) and ESI-collision activated reaction/collision induced dissociation (ESI-CAR/CID) mass spectrometric investigation, combined with quantum chemistry calculations, to elucidate the reaction mechanism of [2+1] cycloaddition between alkyne and norbornadiene using a Pd(II) complex as catalyst. The coordination mode of alkyne on the metal was shown to be an essential preliminary step of the reaction, but mass spectrometric results were difficult to rationalize according to changes in the experimental conditions. In this work we present a detailed RRKM modeling of these experiments using MassKinetics software. We demonstrate how essential kinetic modeling is in order to interpret these experiments: both for phenomenological aspects (understand spectra and changes in their pattern due to energetic modifications) and as a link between quantum chemistry results and tandem MS experiments. Complete energy profile for isomerization and decomposition processes of [Pd[(t-Bu)(Ph)PO]2H+PhCCH]+ complexes has been determined through kinetic modeling of experimental data.Detailed modeling procedure is presented; approximations discussed and validated for quantitative comparison with quantum chemistry calculations. Agreement between isomerization barriers determined with kinetic modeling of experimental data and those determined through quantum chemistry was found to be within few kcal/mol supporting the validity of the approach and assumptions made in the model.

DFT Study of Dissociative Adsorption of Hydrogen Sulfide on Cu(111) and Au(111)

Density functional theory (DFT) is used to investigate the reaction pathways for H2S adsorption on Au(111) and Cu(111) at low coverage as well as the full decomposition of H2S on Cu(111). On both surfaces, a weakly bonded molecular state is found with the S atom bond on top sites being molecular adsorption, a nonactivated process. The H-SH dissociation process is endothermic on Au(111), and all reaction pathways present high activation energy barriers which explains the extremely low dissociation probability of H2S on defect-free Au(111) estimated from experiments. This scenario slightly changes for H2S/Cu(111): (i) dissociated configurations are energetically more favorable than the molecular state and (ii) the H-SH bond cleavage process presents a relatively small activation energy barrier. This is not inconsistent with low but nonzero reactive sticking probability of thermal H2S molecules reported in experiments. The complete energy profile for the H2S adsorption and full decomposition is compatible with the accumulation of S-adatoms observed experimentally.

Low-temperature IR and NMR studies of the interaction of group 8 metal dihydrides with alcohols.

The reactions of the octahedral dihydrido complexes [MH(2)(PP(3))] [M=Fe, Ru, Os; PP(3)=P(CH(2)CH(2)PPh(2))(3)] with a variety of weak ROH acids have been studied by IR and NMR methods in either CH(2)Cl(2) or THF in the temperature range from 190 to 290 K. This study has allowed the determination of the spectral and thermodynamic properties associated with the formation of dihydrogen bonds (DHB) between the terminal hydrides and the OH group. Both the DHB enthalpy values and the hydride basicity factors (E(j)) have been found to increase in the order Fe < Ru < Os. The proton transfer process, leading to the DHB complexes, and eventually to eta(2)-H(2) products, has been found to depend on the acidic strength of the alcohol as well as the nature of the solvent. Low temperature IR and NMR techniques have been used to trace the complete energy profile of the proton transfer process involving the osmium complex [OsH(2)(PP(3))] with trifluoroethanol.

Wheelchair racing efficiency

Purpose : For individuals with disabilities exercise, such as wheelchair racing, can be an important modality for community reintegration, as well as health promotion. The purpose of this study was to examine selected parameters during racing wheelchair propulsion among a sample of elite wheelchair racers. It was hypothesized that blood lactate accumulation and wheeling economy (i.e. oxygen consumed per minute) would increase with speed and that gross mechanical efficiency would reach an optimum for each athlete. Method : Twelve elite wheelchair racers with paraplegia participated in this study. Nine of the subjects were males and three were females. Each subject used his or her personal wheelchair during the experiments. A computer monitored wheelchair dynamometer was used during all testing. The method used was essentially a discontinuous economy protocol. Mixed model analysis of variance (ANOVA) was used to compare blood lactate concentration, economy (minute oxygen consumption), and gross mechanical efficiency across the stages. Results : The results of this study show that both economy and blood lactate concentration increase linearly with speed if resistance is held constant. The subjects in this study had gross mechanical efficiencies (gme) of about 18%, with the range going from 15.222.7%. The results indicate that at the higher speeds of propulsion, for example near race speeds, analysis of respiratory gases may not give a complete energy profile. Conclusion : While there is a good understanding of training methods to improve cardiovascular fitness for wheelchair racers, little is known about improving efficiency (e.g. technique, equipment), therefore methods need to be developed to determine efficiency while training or in race situations.

A Mechanistic Study of the Brønsted-Acid Catalysis ofn-Hexane → Propane + Propene, Featuring Carbonium Ions

A hypothetical five-step catalytic cycle for Brønsted-mediated fission of an all-trans n-alkane was examined using density functional theory. Optimized geometries and transition states were determined for catalyst−reactant complexes, using three different monodentate catalyst ions (NH4+, H3O+, and H2F+). Despite the wide variety of catalyst acidities, protonated hexane appears as an intermediate (not a transition state) in each case. The protonated cyclopropane structure is the most likely initial form of the dissociated product ion. The predicted intermediates were seen to vary with catalyst acidity. The complete energy profiles of this model catalytic cycle are provided and fitted to a cosine expansion, which allows for generation of the energy profile for any Brønsted catalyst and any n-alkane only on the basis of the proton affinities of the n-alkane and the conjugate base of the catalyst. Remarks on the applicability to zeolites and ionic liquid catalysts are given.

Energy profile of rapid, reversible oxidative addition reaction

The trimethyltin undergo a very fast, reversible oxidative addition reaction with [PtMe2(Bu2bipy)], Bu2bipy = 4,4′-di-tert-butyl-2,2′-bipyridine, to give [PtXMe2(SnMe3)(Bu2bipy)] for which a complete energy profile can be obtained by using variable-temperature NMR methods; the reaction with X = I is the fastest known oxidative addition and activation energies when X = Cl suggest detailed structure for the transition state.

Estimation of changes in side chain configurational entropy in binding and folding: General methods and application to helix formation

Theoretical estimations of changes in side chain configurational entropy are essential for understanding the different contributions to the overall thermodynamic behavior of important biological processes like folding and binding. The configurational entropy of any given side chain in any particular protein can be evaluated from the complete energy profile of the side chain. Calculations of the energy profiles can be performed using the side chain single bond dihedrals as the only independent variables as long as the structures at each value of the dihedrals are allowed to relax through small changes in the valence bond angles. The probabilities of different side chain conformers obtained from these energy profiles are very similar to the conformer populations obtained by analysis of side chain preferences in the proteins of the Protein Data Bank. Also, side chain conformational entropies obtained from the energy profiles agree extremely well with those obtained from the Protein Data Bank conformer populations. Changes in side chain configurational entropy in binding and folding can be computed as differences in conformational entropy because, in most cases, the frequency of the rotational oscillation around the energy minimum of any given conformer does not appear to change significantly in the reactions. Changes of side chain conformational entropy calculated in this way were compared with experimental values. The only available experimental data--the effect of side chain substitution on the stability of alpha-helices--were used for this comparison. The experimental values were corrected to subtract the solvent contributions. This comparison yields an excellent agreement between calculated and experimental values, validating not only the theoretical estimates but also the separability of the entropic contributions into configurational terms and solvation related terms.

Complete energy profile of a chiral propeller compound: Tris-(2′-methylbenzimidazol-1′-yl) Methane (TMBM). Chromatographic resolution on triacetyl cellulose, x-ray structures of the racemic and one enantiomer, and dynamic NMR study

Tris-(2′-methylbenzimidazol-1 ′-y) methane (TMBM) presents an interesting example of propeller-like chirality, which is discussed according to Mislow's and Dunitz's descriptions. Fortunately, the two most stable isomers (the three methyl groups “up”, i . e . on the same side of the methine proton, and two methyl groups “up” and the third one “down”) were present in the solid state, thus allowing the determination of their molecular structure by x-ray crystallography. The activation barrier which separates both isomers (9.8 kcal.mol −1) was determined by dynamic 1H n.m.r., whereas that corresponding to enantiomers (28.5 kcal. mol −1) was determined kinetically by racemization, after pure enantiomers were resolved by chromatography on microcrystalline triacetyl cellulose. Both the racemic TMBM and its enantiomers crystallize with a larger number of water molecules, six and seven respectively, forming cyclic structures.

Rhodopsin photoenergetics: lumirhodopsin and the complete energy profile

1. Introduction Various intermediate stages in the photolysis of visual pigments have been recognised, but neither their stereochemical form nor their relation to the actual process of visual excitation have been resolved (review [I]). The relative energies of many of the intermedi- ates in the bovine rhodopsin bleaching sequence have been determined in recent years by direct photocalo- rimetric methods [2-I]. Here I report the measure- ment of the enthalpy change associated with the light- induced formation of lumirhodopsin in bovine photo- receptor membranes at -75°C. This completes the sequence of calorimetrically accessible intermediates, and allows construction of an energy profile for the entire process which establishes firm thermodynamic constraints for proposed molecular mechanisms. 2. Materials and methods Bovine rod outer segment membranes (ROS) were prepared by a standard sucrose density gradient tech- nique [5] from the retinas of fresh, dark-adapted cattle eyes, obtained locally. Samples for photocalo- rimetry were prepared by suspension of ROS in a mixture of glycerol (2 vol.) and 0.1 M sodium phos- phate buffer (1 vol.), pH 7.2 at room temperature. Rhodopsin concentrations and the extent of bleaching during calorimetry were determined from room tem- perature absorbance spectra of aliquots of the ROS suspension dispersed in 2% (w/v) CTAB (cetyltrimeth- ylammonium bromide, Sigma Chem. Co.), 0.1 M phosphate buffer, pH 7 .?I, containing 10 mM hydrox- ylamine hydrochloride, assuming a molar extinction coefficient of 41 000 at 500 nm. Unless otherwise stated, all operations were performed in the dark or under dim red light. 324 Instrumental details of the low-temperature photo- calorimeter have appeared in [3,6]. For these experi- ments the entire calorimetric unit was surrounded by a copper circulation coil and suspended in a Dewar vessel filled with methanol. The system was further insulated with expanded polystyrene foam and mounted in a temperature-controlled ( 20 f 1°C) darkroom. The calorimeter was cooled to -75°C by circulation of methanol from a low-temperature bath, modified for proportional temperature control with a Pt resistance probe and precision electronic controller. Sample illumination was via glass fibre optics from a grating monochromator and a stabilised 200 W xenon arc lamp. Electrical calibration gave an instrumental sensitivity of 0.071 pV/pW under these conditions. The amplified signal, integrated over 60 s intervals, was recorded digitally as a function of time through- out an experiment. In a typical experiment the photocalorimeter was loaded with 2 .O ml ROS suspension (Esoo = 1) together with a reference sample of the same material totally bleached at room temperature prior to loading. After thermal equilibration at -75°C for several hours (usually overnight) the sample was irradiated briefly at 480 or 520 nm and the differential thermal response recorded. The sample was then removed, warmed to room temperature, and an aliquot taken for spectral determination of the amount of photoreaction in comparison with starting material. Control experi- ments included trials with bleached material in both calorimeter cells. 3. Results and discussion Lumirhodopsin is the kinetically stable photo- product of bovine rhodopsin at -75°C and the reac- tion only proceeds to subsequent stages on warming