Transition State Energy Barrier Research Articles

Sulfur-Promoted Hydrocarboxylation of Olefins on Heterogeneous Single-Rh-Site Catalysts

Sulfur poisoning is a severe problem in industrial applications, attracting broad interest in fundamental research studies. Although a number of studies about sulfur resistance have been implemented in many reactions on nanoparticle catalysts, few investigations focus on carbonylation reactions using heterogeneous single-metal-site catalysts (HSMSCs). Herein, we present an unanticipated sulfur-promoted performance in olefin hydrocarboxylation reactions on a single-Rh-site catalyst supported on porous ionic polymers (Rh1/PIPs) with 1000 ppm H2S in CO feed. Ex situ EXAFS and in situ DRIFTS revealed a ternary cycle mechanism of olefin hydrocarboxylation reactions with Rh–H complexes as predominant active species in both pure and H2S-containing feedstock. Moreover, the transformation of the Rh mononuclear complex with the addition of H2S was also demonstrated. Density functional theory studies were performed to verify the feasibility of the proposed pathway and confirm that the energy barriers of transition states with the sulfur ligand were much lower than those in normal feed, for example, a decline of 3.4 kcal/mol for the rate-determining step of migration and insertion of CO. This work provides a distinctive example for the insight of sulfur effect on carbonylation, which could be potentially beneficial for further applications of HSMSCs.

Theory-guided oxygen-vacancy for enhancing H2S sensing performance of NiO

As a stable and promising metal oxide semiconductor, NiO has been developed in gas-sensing field. However, the low sensitivity of p-type semiconductor metal oxides hinders their wide application in the sensing field. Herein, we report the introduction of oxygen vacancies into NiO to adjust its electronic structure and adsorption energies for H2S, HS, S, and H species. The corresponding theoretical results indicate that the oxygen vacancies acted as unsaturated and active sites can directly change the electronic structure of NiO and further enhance the sensing performances of H2S by decreasing the transition state energy barriers of H2S and HS species respectively dissociated into HS/H species and S/H species on the surface of NiO. Subsequently, the sensing experiments and ex-situ XPS analysis reveal the enhanced H2S sensing mechanism of NiO by introducing oxygen vacancies. In general, the sensing characteristics and sensing mechanism of NiO for H2S were systematically studied through theoretical calculations and experimental phenomena. This work will promote the development of design of oxygen vacancy in MOS sensors and provide new way for revealing the sensing mechanism.

Mechanistic Studies of the Catalytic Reduction of CO2 to CO: Efficient CO-Releasing Si- and Ge-Based Catalysts.

Besides its significant challenges, efficient catalytic conversion of CO2 to value-added chemicals is highly desired. Herein, we report efficient silicon- and germanium-based catalysts for CO2 activation and its reduction to CO studied using B3LYP-GD3/6-31++G(d,p)/tetrahydrofuran (THF) and M06-2X/6-311++g(d,p)/THF density functional theory methods. The catalysts were systematically designed based on the previously reported silicon- and germanium-based compounds. The germanium-based catalysts are reported for the first time in this study. The calculated transition state energy barriers (5.7–15.8 kcal/mol) indicate that all the catalysts can easily activate CO2. Among all the B3LYP-GD3-calculated transition-state energy barriers, the highest energy barrier found (27.2–28.3 kcal/mol) is for the protonation of the carboxylic acid group of the silacarboxylic and germacarboxylic acids. Once the silacarboxylic and germacarboxylic acids are protonated, the water molecule can easily dehydrate and leave the catalysts with CO. The electrochemical reduction of the M–CO (M = Si and Ge) complexes further enhances the complexes to easily release CO, with all transition state energy barriers being lower than 10 kcal/mol. The results show that both CO2 activation and its reduction to CO using the studied catalysts are thermodynamically and kinetically favorable. This work provides an important insight for CO2 activation and its reduction to CO using earth-abundant and nontoxic main group element-based catalysts.

Fe-Catalyzed CO2 Adsorption over Hexagonal Boron Nitride with the Presence of H2O.

The energy barrier of CO2 chemically adsorbed on hexagonal boron nitride (h-BN) is relatively big. In order to cut down the energy barriers and facilitate fast adsorption of CO2, it is necessary to apply catalysts as a promoter. In this study, single-atom iron is introduced as the catalyst to reduce the energy barriers of CO2 adsorbed on pure/doped h-BN. Through density functional theory calculations, catalytic reaction mechanisms, stability of single-atom iron fixed on adsorbents, CO2 adsorption characteristics, and features of thermodynamics/reaction dynamics during adsorption processes are fully investigated to explain the catalytic effects of single-atom iron on CO2 chemisorption. According to calculations, when CO2 and OH- get into activated states (i.e., CO2•- and •OH) with the help of single-atom iron, their chemical activities will be promoted to a large degree, which makes the transition state (TS) energy barrier of HCO3- to decrease by 92.54%. In the meantime, it is proved that single-atom iron could be stably fixed on doped h-BN with the binding energy larger than 2 eV to achieve sustainable catalysis. With the presence of single-atom iron, TS energy barriers of CO2 adsorbed on h-BN with the presence of H2O decreased by 94.39, 78.87, and 30.63% over pure h-BN, 3C-doped h-BN, and 3N-doped h-BN, respectively. In the meantime, thermodynamic analyses indicate that TS energy barriers are mainly determined by element doping and temperatures are a little beneficial to the reduction of TS energy barriers. With the above aspects combined, the results of this study could supply crucial information for massively and quickly capturing CO2 in real industries.

Understanding the dehydrogenation mechanism over iron nanoparticles catalysts based on density functional theory

The conversion of chemical feedstock materials into high value-added products accompanied with dehydrogenation is of great value in the chemical industry. However, the catalytic dehydrogenation reaction is inhibited by a limited number of expensive noble metal catalysts and lacks understanding of dehydrogenation mechanism. Here, we report the use of heterogeneous non-noble metal iron nanoparticles (NPs) incorporated mesoporous nitrogen-doped carbon to investigate the dehydrogenation mechanism based on experiment observation and density functional theory (DFT) method. Fe NPs catalyst displays excellent performance in the dehydrogenation of 1,2,3,4-tetrahydroquinoline (THQ) with 100% selectivity and 100% conversion for 10−12 h at room temperature. The calculated adsorption energy implies that THQ prefers to adsorb on Fe NPs as compared with absence of Fe NPs. What is more, the energy barrier of transition state is relatively low, illustrating the dehydrogenation is feasible. This work provides an atomic scale mechanism guidance for the catalytic dehydrogenation reaction and points out the direction for the design of new catalysts.

Doubly-Charged Negative Ions as Novel Tunable Catalysts: Graphene and Fullerene Molecules Versus Atomic Metals.

The fundamental mechanism underlying negative-ion catalysis involves bond-strength breaking in the transition state (TS). Doubly-charged atomic/molecular anions are proposed as novel dynamic tunable catalysts, as demonstrated in water oxidation into peroxide. Density Functional Theory TS calculations have found a tunable energy activation barrier reduction ranging from 0.030 eV to 2.070 eV, with Si2−, Pu2−, Pa2− and Sn2− being the best catalysts; the radioactive elements usher in new application opportunities. C602− significantly reduces the standard C60− TS energy barrier, while graphene increases it, behaving like cationic systems. According to their reaction barrier reduction efficiency, variation across charge states and systems, rank-ordered catalysts reveal their tunable and wide applications, ranging from water purification to biocompatible antiviral and antibacterial sanitation systems.

Reactivity of Cobalt Clusters Con±/0 with Ammonia: Co3+ Cluster Catalysis for NH3 Dehydrogenation.

A customized reflection time-of-flight (Re-TOF) mass spectrometer combined with a 177 nm deep-ultraviolet laser has enabled us to observe well-resolved cobalt clusters Con±/0 and perform a comprehensive study of their reactivity with ammonia (NH3). The anions Con- are found to be inert, the neutrals allow the adsorption of multiple NH3 molecules, while the cationic Con+ clusters readily react with NH3 giving rise to dehydrogenation. However, incidental dehydrogenation of NH3 on Con+ is only observed for n ≥ 3. The dramatic charge- and size-dependent reactivities of Con±/0 clusters with NH3 are studied by the density functional theory (DFT)-calculation results of energetics, density of states, orbital interactions, and reaction dynamics. We illustrate the dehydrogenation from two NH3 molecules, where a significantly reduced transition-state energy barrier is found pertaining to the dimolecular co-catalysis effect. The reactivity of Co3+ with NH3 is illustrated showing effective catalysis for N-H dissociation to produce hydrogen applicable for designing ammonia fuel cells.

Domain Separated Density Functional Theory for Reaction Energy Barriers and Optical Excitations.

We recently proposed domain separated density functional theory (DS-DFT), a framework that allows for the combination of different levels of theory for the computation of the electronic structure of molecules. This work discusses the application of DS-DFT to the computation of transition-state energy barriers and optical absorption spectra. We considered several hydrogen abstraction reactions and optical spectra of molecule/metal cluster systems, including the absorption of individual species such as carbon monoxide, methane, and molecular hydrogen to a Li6 cluster. We present and discuss two domain-separated methods: (i), the screened-density approximation (SDA) and (ii) linearly weighted exchange (LWE). We find that SDA, which is applied as a hybridization based on atomic domains, could be useful to computing energy barriers, whereas LWE is suited for the analysis of electronic properties such as ground-state gaps, excitation energies, and oscillator strengths.

Iodization Threshold in Size-Dependent Reactions of Lead Clusters Pbn+ with Iodomethane.

Utilizing a magnetron-sputtering (MagS) source in tandem with a multiple-ion laminar flow tube (MIFT) reactor and a customized triple quadrupole mass spectrometer (TQMS), we have prepared clean Pbn+ (n = 1-13) clusters and measured their reactivity with iodomethane under high carrier gas pressures. Strong size dependences are found for the reactivity of these cationic Pbn+ clusters with CH3I. For the Pbn+ with n ≤ 4, iodinated clusters PbnI+ were found to be the dominant products, in strong contrast to n > 4 where no such products were seen. Quantum chemical studies show that with an increasing number of Pb atoms, the Pb-Pb interatomic interactions become stronger compared with the Pb-I bonding in PbnI+ clusters. Furthermore, the reactions of Pb1-4+ with CH3I have fairly small transition state energy barriers, in contrast to those for Pbn>4+ clusters which have magnitudes that will prevent reactions under the ambient conditions.

Biosynthesis of Grandione: An Example of Tandem Hetero Diels-Alder/Retro-Claisen Rearrangement Reaction?

Mechanistic theoretical studies about the feasibility of the traditional proposed mechanism of formation for icetexane diterpene dimer grandione were assessed using density functional method at the M06-2X/6-31G(d,p) level of theory. Bulk water solvent effects were taken into account implicitly using the polarizable continuum model (SCI-PCM). The results were compared with the selectivity found in the biomimetic synthesis performed by experimental research groups. The relative free energy calculation shows that the one-step H-DA formation mechanism nominated in the literature is not a viable mechanism. We found that an alternative competing Tandem pathway is consistent with the experimental trends. Thus, our results suggested that the compound grandione is formed via a H-DA/retro-Claisen rearrangement and not by the traditional H-DA mechanism proposed early in the experimental studies. The H-DA initial step produce a biecyclic adduct followed by a domino retro-Claisen rearrangement that releases the energy strain of the bicyclic intermediary. Steric issues and hyperconjugation interactions are the mainly factors driving the reaction nature and the selectivity in the formation reaction. Finally, the enzymatic assistance for dimer formation was analyzed in terms of the calculated transition state energy barrier.

Improvement of l -asparaginase thermal stability by regulating enzyme kinetic and thermodynamic states

Abstract l -asparaginase (EC 3.5.1.1) needs to endure high temperatures during applications in food processing. We here improved the thermal stability of Bacillus subtilis 168 l -asparaginase by regulating both the kinetic and thermodynamic states of the enzyme. According to the molecular dynamics simulation for l -asparaginase, 10 flexible residues potentially affecting the kinetic stability were individually subjected to saturation mutagenesis, generating two highly stabilized mutants, S180N and D289T. As predicted by Discovery Studio, eight residues of l -asparaginase formed multiple unfavourable charge–charge interactions adversely affecting thermodynamic stability. Single-site saturation mutagenesis on these residues resulted in two thermodynamically stabilized mutants, E260F and E292S. Using these mutants, we constructed a further stabilized quadruple mutant NTFS (S180N/D289T/E260F/E292S). Compared with the wild-type enzyme, NTFS exhibited an 8.1-fold increase in half-life at 65 °C and a 5.56 °C increase in melting temperature. NTFS also showed a substantial increase in the transition state energy barrier (ΔΔGtransition = 5.27 KJ/mol) and a clear decrease in folding free energy (ΔΔGfolding = −19.12 kcal/mol) relative to the wild-type enzyme. These results indicated that simultaneous regulation of both the kinetic and thermodynamic states of an enzyme represents an efficient strategy for enhancing thermal stability. The highly stable NTFS described here might be beneficial for industrial application.

Atomic-Scale Core/Shell Structure Engineering Induces Precise Tensile Strain to Boost Hydrogen Evolution Catalysis.

Tuning surface strain is a new strategy for boosting catalytic activity to achieve sustainable energy supplies; however, correlating the surface strain with catalytic performance is scarce because such mechanistic studies strongly require the capability of tailoring surface strain on catalysts as precisely as possible. Herein, a conceptual strategy of precisely tuning tensile surface strain on Co9 S8 /MoS2 core/shell nanocrystals for boosting the hydrogen evolution reaction (HER) activity by controlling the MoS2 shell numbers is demonstrated. It is found that the tensile surface strain of Co9 S8 /MoS2 core/shell nanocrystals can be precisely tuned from 3.5% to 0% by changing the MoS2 shell layer from 5L to 1L, in which the strained Co9 S8 /1L MoS2 (3.5%) exhibits the best HER performance with an overpotential of only 97 mV (10 mA cm-2 ) and a Tafel slope of 71 mV dec-1 . The density functional theory calculation reveals that the Co9 S8 /1L MoS2 core/shell nanostructure yields the lowest hydrogen adsorption energy (∆EH ) of -1.03 eV and transition state energy barrier (∆E2H* ) of 0.29 eV (MoS2 , ∆EH = -0.86 eV and ∆E2H* = 0.49 eV), which are the key in boosting HER activity by stabilizing the HER intermediate, seizing H ions, and releasing H2 gas.

Biogenesis of Triterpene Dimers from Orthoquinones Related to Quinonemethides: Theoretical Study on the Reaction Mechanism.

The biogenetic origin of triterpene dimers from the Celastraceae family has been proposed as assisted hetero-Diels-Alder reaction (HDA). In this work, computational calculation of HDA between natural quinonemethides (tingenone and isopristimerol) and hypothetical orthoquinones has been performed at the M06-2X/6-31G(d) level of theory. We have located all the HDA transition states supporting the biogenetic route via HDA cycloadditions. We found that all reactions take place through a concerted inverse electron demand and asynchronous mechanism. The enzymatic assistance for dimer formation was analyzed in terms of the calculated transition state energy barrier.

Uniporter substrate binding and transport: reformulating mechanistic questions.

Transporters are involved in material transport, signaling, and energy input in all living cells. One of the fundamental questions about transporters is concerned with the precise role of their substrate in driving the transport process. This is particularly important for uniporters, which must utilize the chemical potential of substrate as the only energy source driving the transport. Thus, uniporters present an excellent model for the understanding of how the difference in substrate concentration across the membrane is used as a driving force. Local conformational changes induced by substrate binding are widely considered as the main mechanism to drive the functional cycle of a transporter; in addition, reducing the energy barrier of the transition state has also been proposed to drive the transporter. However, both points of view require modification to allow consolidation with fundamental thermodynamic principles. Here, we discuss the relationship between thermodynamics and kinetics of uniporters. Substrate binding-induced reduction of the transition-state energy barrier accelerates the transport process in kinetic terms, while the chemical potential of the substrate drives the process thermodynamically.

Why p-OMe- and p-Cl-β-Methylphenethylamines Display Distinct Activities upon MAO-B Binding.

Despite their structural and chemical commonalities, p-chloro-β-methylphenethylamine and p-methoxy-β-methylphenethylamine display distinct inhibitory and substrate activities upon MAO-B binding. Density Functional Theory (DFT) quantum chemical calculations reveal that β-methylation and para-substitution underpin the observed activities sustained by calculated transition state energy barriers, attained conformations and key differences in their interactions in the enzyme’s substrate binding site. Although both compounds meet substrate requirements, it is clear that β-methylation along with the physicochemical features of the para-substituents on the aromatic ring determine the activity of these compounds upon binding to the MAO B-isoform. While data for a larger set of compounds might lend generality to our conclusions, our experimental and theoretical results strongly suggest that the contrasting activities displayed depend on the conformations adopted by these compounds when they bind to the enzyme.

Domain Configuration Defines the Thermodynamic Landscape of Elongation Factor Tu Nucleotide Binding

During protein synthesis Elongation Factor (EF) Tu plays a critical role in maintaining translational fidelity. EF-Tu functions as a molecular switch gating, in a nucleotide-dependent manner, the entrance of aminoacyl (aa)-tRNA into the translating ribosome. Correct codon-anticodon interaction stimulates EF-Tu to hydrolyze GTP to GDP and P i which is followed by a conformational change releasing the bound aa-tRNA. To prevent premature nucleotide exchange on the ribosome EF-Tu has evolved a 60-fold higher affinity for GDP than GTP (1). To this end we investigate what thermodynamic and structural features of EF-Tu give rise to these differences in nucleotide affinity, investigating how this property of EF-Tu contributes to translational fidelity. Here we report a rapid kinetics analysis using the stopped-flow technique to measure the temperature dependence of the rate constants describing nucleotide association and dissociation. This has allowed us to determine the thermodynamic parameters governing these processes. We find that EF-Tu’s affinity to GTP and GDP differ mainly due differences in the transition state energy barriers of dissociation and not association. In addition, we observe that formation of the EF-Tu•GDP complex is enthalpically favored while the EF-Tu•GTP complex is entropically favored. This is consistent with our previous work reporting that the GTP dissociation is entropically driven (2). To provide a structural interpretation of the different thermodynamic contributions to nucleotide binding, we utilized Molecular Dynamic simulations of EF-Tu in its respective nucleotide bound forms. From these simulations we have identified a highly dynamic and transient hydrogen-bonding network that spans all domains of EF-Tu as the likely contributor to stabilizing the GDP conformation, whereas differences in water coordination defined by domain arrangement favor the GTP conformation. Our findings show that EF-Tu has evolutionarily modulated both the entropic and enthalpic contributions to the transition state barrier of nucleotide dissociation by modulating domain configuration in order for the fine-tuning of nucleotide-binding affinities. (1) Kiril B. Gromadzki, Hans-Joachim Wieden, and Marina V. Rodnina. Kinetic mechanism of Elongation Factor Ts-Catalyzed nucleotide exchange in Elongation Factor Tu. Biochemistry 41 , 162-169 (2002). (2) Evan Mercier, Dylan Girodat, Hans-Joachim Wieden. A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu. Scientific Reports 5 , 1-9 (2015).

A Conserved Residue Cluster That Governs Kinetics of ATP-dependent Gating of Kir6.2 Potassium Channels

ATP-sensitive potassium (KATP) channels are heteromultimeric complexes of an inwardly rectifying Kir channel (Kir6.x) and sulfonylurea receptors. Their regulation by intracellular ATP and ADP generates electrical signals in response to changes in cellular metabolism. We investigated channel elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of ∼60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp-68 and Lys-170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp-68 or Lys-170 markedly slow the kinetics of channel opening (500 and 700 ms for W68L and K170N, respectively), while increasing channel open probability. Examining the functional effects of these residues using φ value analysis revealed a steep negative slope. This finding implies that these residues play a role in lowering the transition state energy barrier between open and closed channel states. Using unnatural amino acid incorporation, we demonstrate the requirement for a planar amino acid at Kir6.2 position 68 for normal channel gating, which is potentially necessary to localize the ϵ-amine of Lys-170 in the phosphatidylinositol 4,5-bisphosphate-binding site. Overall, our findings identify a discrete pair of highly conserved residues with an essential role for controlling gating kinetics of Kir channels.

Quantitative Connection between Ensemble Thermodynamics and Single-Molecule Kinetics: A Case Study Using Cryogenic Electron Microscopy and Single-Molecule Fluorescence Resonance Energy Transfer Investigations of the Ribosome.

At equilibrium, thermodynamic and kinetic information can be extracted from biomolecular energy landscapes by many techniques. However, while static, ensemble techniques yield thermodynamic data, often only dynamic, single-molecule techniques can yield the kinetic data that describe transition-state energy barriers. Here we present a generalized framework based upon dwell-time distributions that can be used to connect such static, ensemble techniques with dynamic, single-molecule techniques, and thus characterize energy landscapes to greater resolutions. We demonstrate the utility of this framework by applying it to cryogenic electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies of the bacterial ribosomal pre-translocation complex. Among other benefits, application of this framework to these data explains why two transient, intermediate conformations of the pre-translocation complex, which are observed in a cryo-EM study, may not be observed in several smFRET studies.

Evaluating AM1/d-CB1 for Chemical Glycobiology QM/MM Simulations.

The newly parametrized AM1/d-CB1 is evaluated for its performance in modeling monosaccharide structure, carbohydrate ring pucker, amino acid proton transfer, DNA base pair interactions, carbohydrate-aromatic π interactions, and phosphates that are prominent in glycosyltransferases. The accuracy of the method in these computations is compared to a comprehensive range of NDDO methods commonly used to study glycan structure and reactivity in chemical biology. AM1/d-CB1 shows significant improvement over existing NDDO type methods in the computation of five and six membered carbohydrate ring pucker free energy surfaces. Moreover, the computation of carbohydrate amino acid interactions commonly present in catalytic domains and binding sites are improved over existing NDDO methods. AM1/d-CB1 shows slight improvement for carbohydrate-aromatic π interactions compared to a commonly used NDDO method (AM1). The method is applied to a glycosyltransferase reaction, where it is the only NDDO method able to achieve an optimized reaction profile. Moreover, a comparison of the geometry optimized computations of the reaction scheme give a transition state energy barrier that best compares with DFT (MPW1K). Overall, AM1/d-CB1 is shown to significantly improve on existing NDDO methods in modeling chemical glycobiological events.

An Intramolecular Interaction Controls a Rate-Limiting Step in ATP-Dependent Gating of Kir6.2 Channels

ATP-sensitive potassium (KATP) channels are complexes of inwardly-rectifying Kir channels (Kir6.x) and sulfonylurea receptors (SUR). These two subunits work together to encode sensitivity to intracellular adenine nucleotides (ATP and ADP) and other regulatory ligands including PIP2. We investigated the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels rapidly re-open after washout of ATP, with a time constant of ∼60 ms. Extending similar kinetic measurements to mutants around the bundle crossing revealed modest effects on gating kinetics despite significant changes in ATP sensitivity. However, we identified a pair of highly conserved neighboring amino acids (Trp68, Lys170) that controls the rate of channel recovery and inhibition by ATP. Mutations of Trp68 or Lys170 have the paradoxical effect of dramatically slowing the kinetics of channel opening, while increasing channel open probability. Formalization of the transition state effects of these residues using phi-value analysis revealed a consistent steep negative slope. This finding implies that these residues play a specific role in lowering the transition state energy barrier between open and closed channel states. The demonstration of a negative phi-value is unique for an ion channel gating process, and diverges from interpretations that use phi-values to place specific residues in the spatial and temporal progression through the transition energy landscape. Using nonsense suppression for unnatural amino acid incorporation, we demonstrate the requirement for a planar amino acid at Kir6.2 position 68, potentially required to localize the e-amine of Lys170 in the PIP2 binding site. Our findings identify a discrete pair of residues with an essential role for controlling gating kinetics of Kir channels.