Center for Molecular Modeling - S.L. Moors

Influence of solvation and dynamics on the mechanism and kinetics of nucleophilic aromatic substitution reactions in liquid ammonia

michel — Fri, 06 Nov 2015 09:06:31 +0000

S.L. Moors, B. Brigou, D. Hertsen, P. Balazs, P. Geerlings, V. Van Speybroeck, S. Catak, F. De Proft

Journal of Organic Chemistry

81 (4), 1635-1644

2016

Abstract

The role of the solvent and the influence of dynamics on the kinetics and mechanism of the SNAr reaction of several halonitrobenzenes in liquid ammonia, using both static calculations and dynamic ab initio molecular dynamics simulations, are investigated. A combination of metadynamics and committor analysis methods reveals how this reaction can change from a concerted, one-step mechanism in gas phase to a stepwise pathway, involving a metastable Meisenheimer complex, in liquid ammonia. This clearly establishes, among others, the important role of the solvent and highlights the fact that accurately treating solvation is of crucial importance to correctly unravel the reaction mechanism. It is indeed shown that H-bond formation of the reacting NH3 with the solvent drastically reduces the barrier of NH3 addition. The halide elimination step, however, is greatly facilitated by proton transfer from the reacting NH3 to the solvent. Furthermore, the free energy surface strongly depends on the halide substituent and the number of electron-withdrawing nitro substituents.

DOI

http://dx.doi.org/10.1021/acs.joc.5b02794

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acs%2Ejoc%2E5b02794.pdf

Shape-selective diffusion of olefins in 8-ring solid acid microporous zeolites

michel — Fri, 19 Jun 2015 20:01:35 +0000

A. Ghysels, S.L. Moors, K. Hemelsoet, K. De Wispelaere, M. Waroquier, G. Sastre, V. Van Speybroeck

Journal of Physical Chemistry C

119, 41, 23721-23734

2015

Abstract

The diffusion of olefins through 8-ring solid acid microporous zeolites is investigated using molecular dynamics simulations techniques and using a newly developed flexible force field. Within the context of the Methanol to Olefin (MTO) process and the observed product distribution, knowledge on the diffusion paths is essential to obtain molecular level control over the process conditions. Eight-ring zeotype materials are favorably used for the MTO process as they give a selective product distribution towards low carbon olefins. To investigate how composition, acidity and flexibility influence the diffusion paths of ethene and propene, a series of isostructural aluminosilicates (zeolites) and silicoaluminophosphates (AlPOs and SAPOs) are investigated with and without randomly distributed acidic sites. Distinct variations in diffusion of ethene are observed in terms of temperature, composition, acidity, and topology (AEI, CHA, AFX). In general, diffusion of ethene is an activated process for which free energy barriers for individual rings may be determined. We observe ring dependent diffusion behavior which can not solely be described in terms of the composition and topology of the rings. A new descriptor had to be introduced namely the accessible window area (AWA), inspired by implicit solvation models of proteins and small molecules. The AWA may be determined throughout the molecular dynamics trajectories and correlates well with the number of ring crossings at the molecular level and the free energy barriers for ring crossings from one cage to the other. The overall observed diffusivity is determined by molecular characteristics of individual rings for which AWA is a proper descriptor. Temperature-induced changes in framework dynamics and diffusivity may be captured by following the new descriptor throughout the simulations.

Open Access version available at UGent repository

Green Open Access

DOI

http://dx.doi.org/10.1021/acs.jpcc.5b06010

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How zeolitic acid strength and composition alter the reactivity of alkenes and aromatics towards methanol

michel — Wed, 10 Sep 2014 11:53:49 +0000

M.W. Erichsen, K. De Wispelaere, K. Hemelsoet, S.L. Moors, T. Deconinck, M. Waroquier, S. Svelle, V. Van Speybroeck, U. Olsbye

Journal of Catalysis

328, 186-196

2015

Abstract

This work encompasses a combined experimental and theoretical assessment of how zeolitic acid strength and composition affects acid-catalysed methylation reactions. Overall, higher methylation rates were observed over the material with higher acid strength. Co-reactions of methanol with benzene at 250 degrees C over the two isostructural AFI materials H-SSZ-24 and H-SAPO-5 revealed large differences in selectivity. While the stronger acidic H-SSZ-24 mainly produced toluene and polymethylbenzenes, high yields of C4+ aliphatics were observed over H-SAPO-5. These results strongly suggest that alkene methylation was preferred over H-SAPO-5 even at very low conversion during methanol/benzene co-reactions. Furthermore, a comparison of benzene and propene methylation at 350-400 degrees C revealed a significantly faster rate of benzene than propene methylation in H-SSZ-24, whereas the rates of benzene and propene methylation were similar in H-SAPO-5. The observed difference in reactivity of the two hydrocarbons in both catalysts could be understood by careful analysis of various molecular dynamics simulations of the co-adsorbed complexes. The probability to form protonated methanol was, as expected, higher in the more acidic material. However, in H-SSZ-24, the probability for methanol protonation was higher when co-adsorbed with benzene than when co-adsorbed with propene, while the same was not observed in H-SAPO-5. Furthermore, it was found that benzene and methanol are more likely to form a reactive co-adsorbed complex in H-SSZ-24 compared to propene and methanol, while the opposite was observed for H-SAPO-5. This work shows that molecular dynamics simulations provide insights into the adsorption behaviour of guest molecules in large pore AFI materials. The obtained insights correlate with the experimentally observed reactivities. (C) 2015 Elsevier Inc. All rights reserved.

Open Access version available at UGent repository

DOI

http://dx.doi.org/10.1016/j.jcat.2015.01.013

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15_JCatalysis_328,186_Erichsen.pdf

Insight into the Formation and Reactivity of Framework-Bound Methoxide Species in H-ZSM-5 from Static and Dynamic Molecular Simulations

jeroen — Fri, 21 Mar 2014 14:19:42 +0000

J. Van der Mynsbrugge, S.L. Moors, K. De Wispelaere, V. Van Speybroeck

ChemCatChem

6 (7), 1906-1918

2014

Abstract

Framework-bound methoxides occur as intermediates in the stepwise mechanism for zeolite-catalyzed methylation reactions. Herein, the formation of methoxides from methanol or dimethyl ether in H-ZSM-5 is investigated by a combination of static and dynamic simulations, with particular focus on the effect of additional water and methanol molecules on the mechanism and kinetics. Metadynamics simulations allow partitioning the reaction path into distinct phases. Proton transfer from the zeolite to the reactants is found to be the rate-limiting phase in the methoxide formation. Additional methanol molecules only assist the proton transfer in the methoxide formation from methanol, whereas the reaction from dimethyl ether does not benefit from methanol assistance. Once formed, methoxides are found to be as reactive toward alkene methylation as methanol and dimethyl ether.

DOI

http://dx.doi.org/10.1002/cctc.201402146

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Cooperative dynamics of a DNA polymerase replicating complex

sam — Sat, 11 Jan 2014 12:18:47 +0000

S.L. Moors, P. Herdeijn, J. Robben, A. Ceulemans

Biochimica et Biophysica Acta (BBA)

1834 (12), 2554-2563

2013

Published while none of the authors were employed at the CMM

Abstract

Engineered DNA polymerases continue to be the workhorses of many applications in biotechnology, medicine and nanotechnology. However, the dynamic interplay between the enzyme and the DNA remains unclear. In this study, we performed an extensive replica exchange with flexible tempering (REFT) molecular dynamics simulation of the ternary replicating complex of the archaeal family B DNA polymerase from the thermophile Thermococcus gorgonarius, right before the chemical step. The convoluted dynamics of the enzyme are reducible to rigid-body motions of six subdomains. Upon binding to the enzyme, the DNA double helix conformation changes from a twisted state to a partially untwisted state. The twisted state displays strong bending motion, whereby the DNA oscillates between a straight and a bent conformation. The dynamics of double-stranded DNA are strongly correlated with rotations of the thumb toward the palm, which suggests an assisting role of the enzyme during DNA translocation. In the complex, the primer–template duplex displays increased preference for the B-DNA conformation at the n − 2 and n − 3 dinucleotide steps. Interactions at the primer 3′ end indicate that Thr541 and Asp540 are the acceptors of the first proton transfer in the chemical step, whereas in the translocation step both residues hold the primer 3′ terminus in the vicinity of the priming site, which is crucial for high processivity.

DOI

http://dx.doi.org/10.1016/j.bbapap.2013.09.003

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Molecular dynamics kinetic study on the zeolite-catalyzed benzene methylation in ZSM-5

michel — Tue, 20 Aug 2013 18:51:13 +0000

S.L. Moors, K. De Wispelaere, J. Van der Mynsbrugge, M. Waroquier, V. Van Speybroeck

ACS Catalysis

2013 (3), 2556–2567

2013

Abstract

The methylation of arenes is a key step in the production of hydrocarbons from methanol over acidic zeolites. We performed ab initio static and molecular dynamics free energy simulations of the benzene methylation in H-ZSM-5 to determine the factors that influence the reaction kinetics. Special emphasis is given to the effect of surrounding methanol molecules on the methylation kinetics. It is found that for higher methanol loadings methylation may also occur from a protonated methanol cluster, indicating that the exact location of the Brønsted acid site is not essential for the zeolite-catalyzed methylation reaction. However, methylations from a protonated methanol cluster exhibit higher free energy barriers than a methylation from a single methanol molecule. Finally, comparison with a pure methanol solvent reaction environment indicates that the main role of the zeolite during the methylation of benzene is to provide the acidic proton and to create a polar environment for the reaction. The metadynamics approach, which is specifically designed to sample rare events, allows exploring new reaction pathways, which take into account the flexibility of the framework and additional guest molecules in the pores and channels of the zeolite framework. This approach goes beyond the often applied static calculations to determine reaction kinetics.

DOI

http://dx.doi.org/10.1021/cs400706e

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Tryptophan Rotamers as Evidenced by X-Ray, Fluorescence Lifetimes, and Molecular Dynamics Modeling

wim — Wed, 28 Nov 2012 13:41:23 +0000

S.L. Moors, M. Hellings, M. De Maeyer, Y. Engelborghs, A. Ceulemans

Biophysical Journal

91 (3), 816-823

2006

Published while none of the authors were employed at the CMM

DOI

http://dx.doi.org/10.1529/biophysj.106.085100

How Is cis−trans Isomerization Controlled in Dronpa Mutants? A Replica Exchange Molecular Dynamics Study

wim — Wed, 28 Nov 2012 13:33:23 +0000

S.L. Moors, S. Michielssens, C. Flors, P. Dedecker, J. Hofkens, A. Ceulemans

Journal of Chemical Theory and Computation (JCTC)

4 (6), 1012-1020

2008

Published while none of the authors were employed at the CMM

DOI

http://dx.doi.org/10.1021/ct8000359

How Do Rotameric Conformations Influence the Time-Resolved Fluorescence of Tryptophan in Proteins? A Perspective Based on Molecular Modeling and Quantum Chemistry

wim — Wed, 28 Nov 2012 13:31:08 +0000

S.L. Moors, A. Jonckheer, M. De Maeyer, Y. Engelborghs, A. Ceulemans

Current Protein and Peptide Science

9 (5), 427-446

2008

Published while none of the authors were employed at the CMM

DOI

http://dx.doi.org/10.2174/138920308785915236

Tryptophan Conformations Associated with Partial Unfolding in Ribonuclease T1

wim — Wed, 28 Nov 2012 13:27:16 +0000

S.L. Moors, A. Jonckheer, Y. Engelborghs, A. Ceulemans

Biophysical Journal

97 (6), 1778-1786

2009

Published while none of the authors were employed at the CMM

DOI

http://dx.doi.org/10.1016/j.bpj.2009.07.015