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Quantum chemical calculations have been performed to evaluate the adsorption of NO on cobalt in several extraframework environments within ferrierite zeolites. All possible arrangements of the two nearby framework aluminum atoms have been considered for the B and G ferrierite cobalt sites. The cobalt–nitrosyl orientation, i.e., bent versus linear, depends on the local zeolite environment. The enthalpies and free energies of adsorption are also functions of the local zeolite environment. NO adsorption is favored by about 50 kJ/mol on cobalt in the B site compared to the G site. This large difference is attributable to two factors: differences in NO-induced strain on the cobalt–zeolite environments as well as an intrinsic difference based on the coordinative unsaturation of cobalt. A simulation of the temperature-programmed desorption profile reveals three distinct cobalt environments for adsorbed NO, showing the dependence of a macroscopic property that is related to catalytic activity on the local zeolite environment near a metal cation. This observation suggests that the increase in the turnover of NO to N2 per cobalt atom with increasing cobalt loading reported in the literature may be related to the same factors. A detailed analysis of the cobalt–nitrosyl bond was also performed. [Copyright &y& Elsevier]

Cell-free systems are useful tools for prototyping metabolic pathways and optimizing the production of various bioproducts. Mechanistically-based kinetic models are uniquely suited to analyze dynamic experimental data collected from cell-free systems and provide vital qualitative insight. However, to date, dynamic kinetic models have not been applied with rigorous biological constraints or trained on adequate experimental data to the degree that they would give high confidence in predictions and broadly demonstrate the potential for widespread use of such kinetic models. In this work, we construct a large-scale dynamic model of cell-free metabolism with the goal of understanding and optimizing butanol production in a cell-free system. Using a combination of parameterization methods, the resultant model captures experimental metabolite measurements across two experimental conditions for nine metabolites at timepoints between 0 and 24 h. We present analysis of the model predictions, provide recommendations for butanol optimization, and identify the aldehyde/alcohol dehydrogenase as the primary bottleneck in butanol production. Sensitivity analysis further reveals the extent to which various parameters are constrained, and our approach for probing valid parameter ranges can be applied to other modeling efforts. • A kinetic model captures timecourse data, including butanol production, in two experimental conditions in cell-free extracts. • Model hypothesizes metabolic mechanisms to explain experimentally observed behaviors between conditions. • Strategies to increase butanol production are predicted, the most promising of which is experimentally validated. • Analyses reveal how model parameters are constrained between many possible parameter sets within an ensemble. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculations were used to study the mechanism of CO2 hydrolysis by Zn-(1,4,7,10-tetraazacyclododecane), also referred to as zinc-cyclen, and evaluate the associated thermodynamic and kinetic parameters. A microkinetic model was then built based on the kinetics and thermodynamics derived from first principles. The model describes the sigmoidal dependence of the observed reaction rate constant on pH, which is similar to behavior observed for CO2 hydrolysis catalysts in nature, i.e., human carbonic anhydrase. The inflection point is identical to the pKa value of the zinc-cyclen complex, in good agreement with previous results. The overall reaction rate constant was calculated to be 3055 M-1 s-1, which is in excellent agreement with the range of experimental values reported (2691.5-3300 M-1 s-1). Importantly, though, the microkinetic model quantifies how the reaction rate and the associated overall rate constant varies as a function of time, underscoring that observed overall rate constants are a function of the species' concentrations used to extract them, which may not be the initial conditions. The decrease in initial reaction rate over 0-12 ms was ascribed to the decrease in the concentration of the catalytic form, Zn-OH-, which was primarily converted to Zn-HCO3-. Through calculating the ratio of the net rate to the forward rate of each elementary reaction, the rate-limiting step of the catalytic cycle was identified as the adsorption of CO2. To aid in the interpretation of the complex microkinetic model, an analytical rate expression was derived based on a simplified potential energy surface comprised of three major regions: the adsorption of CO2, the release of HCO3- via displacement by water, and the deprotonation of Zn-H2O. Analysis showed quantitatively how the observed reaction rate constant depends not only on how fast a CO2 molecule is captured but also on how deep the Zn-HCO3- sits. [ABSTRACT FROM AUTHOR]

Enzyme substrate promiscuity has significant implications for metabolic engineering. The ability to predict the space of possible enzymatic side reactions is crucial for elucidating underground metabolic networks in microorganisms, as well as harnessing novel biosynthetic capabilities of enzymes to produce desired chemicals. Reaction rule-based cheminformatics platforms have been implemented to computationally enumerate possible promiscuous reactions, relying on existing knowledge of enzymatic transformations to inform novel reactions. However, past versions of curated reaction rules have been limited by a lack of comprehensiveness in representing all possible transformations, as well as the need to prune rules to enhance computational efficiency in pathway expansion. To this end, we curated a set of 1224 most generalized reaction rules, automatically abstracted from atom-mapped MetaCyc reactions and verified to uniquely cover all common enzymatic transformations. We developed a framework to systematically identify and correct redundancies and errors in the curation process, resulting in a minimal, yet comprehensive, rule set. These reaction rules were capable of reproducing more than 85% of all reactions in the KEGG and BRENDA databases, for which a large fraction of reactions is not present in MetaCyc. Our rules exceed all previously published rule sets for which reproduction was possible in this coverage analysis, which allows for the exploration of a larger space of known enzymatic transformations. By leveraging the entire knowledge of possible metabolic reactions through generalized enzymatic reaction rules, we are able to better utilize underground metabolic pathways and accelerate novel biosynthetic pathway design to enable bioproduction towards a wider range of new molecules. • Curated a minimal yet comprehensive set of 1224 enzymatic reaction rules. • Can be applied in open-source platforms to design novel biosynthetic pathways. • Redundant and erroneous rules eliminated to enhance computational efficiency. • Outperforms existing rulesets by representing more enzymatic transformations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oligomerization of alkenes upgrades shale gas feedstocks into liquid products. • Microkinetic modelling reveals mechanistic details of propene oligomerization. • The model predicts conversion and selectivity under a range of experimental conditions. • Microkinetic modelling supports catalyst and process optimization. The microkinetic modelling methodology that we developed previously to describe Brønsted acid-catalyzed propene oligomerization on medium-pore MFI zeolites has been extended successfully to large-pore Beta zeolites. The extension of the model was supported by the identification of the key descriptors that account for the different topologies and acid strengths of the zeolite frameworks (physisorption enthalpies, stabilization enthalpies, frequency factors). The model is validated with experimental conversion and selectivity data measured in a plug-flow reactor on a commercial Beta zeolite over a range of operating conditions. Analysis of net reaction rates allowed identifying the preferred pathways that increase oligomerization selectivity toward C 9 species with increasing propene pressure. The model was additionally used to investigate how the stabilization enthalpies of chemisorbed intermediates, an important catalyst descriptor, influenced the selectivity and surface coverage at iso -conversion. This analysis provides mechanistic insights into the propene oligomerization reaction network and its dependence on zeolite topology, and demonstrates how microkinetic models can describe catalyst behaviour and aid in catalyst and process optimization. [ABSTRACT FROM AUTHOR]

There have been many achievements in applying biochemical synthetic routes to the synthesis of commodity chemicals. However, most of these endeavors have focused on optimizing and increasing the yields of naturally existing pathways. We sought to evaluate the potential for biosynthesis beyond the limits of known biochemistry towards the production of small molecule drugs that do not exist in nature. Because of the potential for improved yields compared to total synthesis, and therefore lower manufacturing costs, we focused on drugs for diseases endemic to many resource poor regions, like tuberculosis and HIV. Using generalized biochemical reaction rules, we were able to design biochemical pathways for the production of eight small molecule drugs or drug precursors and identify potential enzyme-substrate pairs for nearly every predicted reaction. All pathways begin from native metabolites, abrogating the need for specialized precursors. The simulated pathways showed several trends with the sequential ordering of reactions as well as the types of chemistries used. For some compounds, the main obstacles to finding feasible biochemical pathways were the lack of appropriate, natural starting compounds and a low diversity of biochemical coupling reactions necessary to synthesize molecules with larger molecular size. [ABSTRACT FROM AUTHOR]

Abstract: Experiments and microkinetic modeling were used to investigate the reaction mechanism of cis-cyclooctene oxidation with H2O2 on heterogeneous manganese 1,4,7-trimethyl-1,4,7-triazacyclononane (Mn–tmtacn) catalysts. A mechanism based on literature reports and model discrimination was identified that captured experimental data well, including data at reaction conditions that were not used for parameter estimation. H2O2 activation on the heterogeneous catalytic complex was identified as the rate-determining step (RDS), and a simple analytical rate expression was derived using the RDS and the pseudo-steady-state approximation for all intermediates. Predicted reaction orders for cis-cyclooctene, water, H2O2, catalyst, and diol and epoxide products are also consistent with experimental observations and can be rationalized according to the derived rate expression. In addition, the ratio of productive to unproductive H2O2 use is analyzed, and catalyst deactivation is found to be an important step in the reaction mechanism that is highly sensitive to temperature. [Copyright &y& Elsevier]

Abstract: Experimental results in the literature show that two metal-organic frameworks (MOFs) containing copper and cobalt nodes are active for hydroperoxide decomposition, which is an important reaction in auto-oxidation processes. Density functional theory (DFT) calculations reported here for these systems suggest that the metal sites in the interior of these MOFs are not the active sites for this type of reaction due to the steric effects of the adjacent linkers. This implies that the experimental catalysis observed may occur on the exterior surface of the MOF crystals. Additional calculations with a copper paddlewheel node show that, despite being able to form complexes with hydroperoxides, the metal sites in copper paddlewheels do not catalyze hydroperoxide decomposition. Preliminary calculations involving undercoordinated metal atoms as a model for metal sites on the MOF exterior crystal surface suggest that these sites could be catalytically active. [Copyright &y& Elsevier]

Abstract: Experiments and microkinetic modeling were used to investigate the kinetics of styrene epoxidation catalyzed by (porphyrin)Mn using iodosylbenzene. While the kinetics follow the general form of Michaelis–Menten rate expressions as proposed in the literature, these simplified rate forms cannot capture all the details of the kinetics simultaneously, most notably catalyst deactivation. In contrast, a microkinetic model based on elementary steps, including deactivation via μ-oxo dimer formation and irreversible degradation, is able to capture experimental data over all reaction times and for different (porphyrin)Mn. Experimentally, we show that encapsulation of (porphyrin)Mn in a supramolecular cavity known as a molecular square significantly reduces catalyst deactivation, which is in agreement with previous experimental studies. Microkinetic modeling also captured the kinetics of this system. Net rate analysis revealed that production of epoxide was primarily due to encapsulated catalysts, and the model was able to quantify the difference in the concentration of deactivated catalyst with and without encapsulation. [Copyright &y& Elsevier]

Abstract: The epoxidation of 1-hexene with titanium silicalite-1 (TS-1) catalyst was investigated to gain insight into the effect of the solvent on the observed reactivity. Three different solvents were examined: methanol, acetonitrile, and acetone. Kinetic data were obtained from batch reaction experiments, with an emphasis placed on gathering more accurate initial rates than those reported in the literature. The dependencies of the rates on the concentrations of 1-hexene, water, and hydrogen peroxide were determined. The adsorption behavior of 1-hexene in TS-1 in the three different solvents was determined independently by batch sorption experiments. Results showed that the solvent has a significant effect on the adsorption of 1-hexene, and hence on the reaction kinetics. Kinetic modeling incorporating experimental and simulated quaternary adsorption isotherms to describe quasi-equilibrated steps revealed that the differences in the observed reaction kinetics may be attributed mostly, but not entirely, to differences of the partitioning of 1-hexene between the bulk and intraporous phases among the three different solvents. [Copyright &y& Elsevier]