DFT Computational Study of the Mechanism of Allyl Halides Carbonylation Catalyzed by Nickel Tetracarbonyl

Abstract: A theoretical investigation at the DFT(B3LYP) level on the carbonylation reaction of allyl bromide catalyzed by nickel tetra-carbonyl Ni(CO)4 is discussed. The computational results show the following: (i) Three main steps characterize the catalytic cycle: (a) an oxidative addition step, (b) a carbonylation step, and (c) a reductive elimination step where the acyl product is obtained and the catalyst is regenerated. (ii) Both Ni(CO)3 and Ni(CO)4 complexes can behave as "active" catalytic species. (iii) The oxidative addition leads to the formation of either η 3 or η 1 -allyl nickel complexes, which are involved in a fast equilibrium. (iv) The carbonylation occurs much more easily on the η 1 than on the η 3 intermediates

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

Study of the reaction mechanism in Mandelate racemase enzyme: reaction path and dynamical sampling approaches

En aquesta tesi s'ha dissenyat i aplicat diferents eines teòriques i computacionals per a l'estudi de la reactivitat de l'enzim Mandelat Racemasa.L'enzim Mandelat Racemasa catalitza la interconversió dels dos enantiòmers (S) i (R) de l'àcid mandèlic a una velocitat semblant. El mecanisme de reacció que es postula experimentalment passa per l'abstracció d'un protó molt poc àcid. Aquesta reacció molt poc favorable en medi aquós l'enzim la catalitza a una velocitat sorprenentment alta.Fent un estudi Mecànica Quàntica / Mecànica Molecular (QM/MM) de la reactivitat de l'enzim s'han trobat els intermedis i les barreres de reacció que permeten deduir tres mecanismes a través dels quals el substracte natural mandelat i altres dos substractes anàlegs poden racemitzar. Expliquem de quina manera l'enzim pot fer la catàlisi tant efectiva i equivalent per als dos enantiòmers.Partint de la necessitat de millorar l'estudi QM/MM anterior, sobretot pel què fa a l'acurada localització dels estats de transició (barreres reacció), s'ha dissenyat un mètode d'optimització d'estructures per ser aplicat a sistemes de milers d'àtoms com ho és el nostre enzim. El mètode anomenat micro-iteratiu es basa en una cerca segons les equacions Rational Function Optimization (RFO) en una zona reduida mentre es minimitza l'entorn amb un mètode computacionalment barat com el LBFGS. Aquest mètode micro-iteratiu ha estat formulat, implementat i testejat en sistemes moleculars grans i petits. Se n'ha estudiat les diferents opcions donant una recepta pràctica per al seu ús en altres reaccions. També se n'ha justificat el seu desenvolupament posant de relleu les millores obtingudes amb aquest nou mètode quan es comparen els nous resultats amb els obtinguts en l'estudi QM/MM inicial.Finalment, l'energia lliure de la reacció enzimàtica s'ha calculat amb tècniques de la dinàmica molecular i de l'Umbrella Sampling. Per aquest tipus de càlcul és imprescindible escollir a priori una coordenada de reacció que permeti anar de reactius a productes, en altres paraules, és necessari saber com té lloc la reacció. Gràcies a la prèvia localització d'estats de transició amb el mètode micro-iteratiu podem conèixer el mecanisme de reacció. I per tant podem emprar una coordenada de reacció adequada que ens permet calcular l'energia lliure de reacció de forma efectiva.In this thesis several theoretical techniques to study the Mandelate Racemase enzyme reactivity are designed and used.The Mandelate Racemase enzyme catalyses the interconversion of both enantiomers (S) and (R) of mandelic acid at apparently the same rate. Experimental results suggest that the reaction mechanism takes place through the abstraction of a non-acid hydrogen. This reaction is very low in aqueous media but the enzyme catalyzes it at an extremely fast rate.We carry out a QM/MM study of the enzyme reativity. We have found the intermediate structures and the energy barriers corresponding to three proposed mechanisms that the natural substrate mandelate and two other substrate analogues may undergo. We are able to explain how the the efficient catalysis is performed for the two enantiomers.Due to the lack in the previous QM/MM study of an efficient method to locate transition state structures (energy barriers) we have designed an structure optimization method to be applied to systems constituted by thousands of atoms such as our enzyme.The so-called micro-iterative method consists in a search based on the Rational Function Optimization (RFO) equations applied in a core zone while the environment is minimized through a computationally affordable method such as LBFGS. The micro-iterative method has been formulated, implemented and tested for small and big molecular systems. We have studied several possible options giving as a result a practical guide for its usage in other reactions. Comparing the results coming from the initial QM/MM study with the ones found by this micro-iterative method we show an improvement that justifies the development.Finally, the free energy corresponding to the enzymatic reaction is calculated by means of Molecular Dynamics and Umbrella Sampling techniques. The free energy computation requires the a priori election of a reaction coordinate that allows the system to go from reactants to products. In other words, it is essential to know how the reaction takes place. Thanks to the accurate search of transition states performed previously by the micro-iterative we can find the reaction mechanism. In this sense we can use an adequate reaction coordinate that permits us an efficient calculation of the reaction free energy

ChemEd X Data dataset

<p>See where this dataset is used here<br>http://chemdata.r.umn.edu </p

Models 360 dataset

<p>This the molecular dataset in JSON format of the Models360 web resource (http://www.chemeddl.org/resources/models360). </p> <p>Models 360 enables users to investigate a collection of 3-D interactive models of organic and inorganic compounds, including extended-structure solids. Users can manipulate the models to examine structure and bonding and demonstrate molecular geometries, vibrations, symmetry, and orbitals. This resource has been built specifically to meet the needs of educators. The molecules and structures shown have been vetted as to their usefulness in teaching, and their accuracy. The structure of each molecule has been calculated using modern quantum mechanical software in order to obtain high-accuracy properties to be used in classrooms.</p> <p>Models 360 was initiated by Xavier Prat-Resina during his period as a postdoctoral fellow with the Chemical Education Digital Library. Major contributions to the project were made by David Pieper, Justin Shorb, Robert Anglin, Brandon Korf, Greg Sovinski, Zak Kastelik, Rachel Bain, Angela Jones, Ieva Reich, Adam Hahn, and John W. Moore, all working for the Chemical Education Digital Library (ChemEd DL).</p> <p> </p

Proton holes in long-range proton transfer reactions in solution and enzymes: A theoretical analysis

Proton transfers are fundamental to chemical processes in solution and biological systems. Often, the well-known Grotthuss mechanism is assumed where a series of sequential “proton hops” initiates from the donor and combines to produce the net transfer of a positive charge over a long distance. While direct experimental evidence for the sequential proton hopping has been obtained recently, alternative mechanisms may be possible in complex molecular systems. To understand these events, all accessible protonation states of the mediating groups should be considered. This is exemplified by transfers through water where the individual water molecules can exist in three protonation states (water, hydronium and hydroxide); as a result, an alternative to the Grotthuss mechanism for a proton transfer through water is to generate a hydroxide by first protonating the acceptor and then transfer the hydroxide towards the donor through water. The latter mechanism can be most generally described as the transfer of a “proton hole” from the acceptor to the donor where the “hole” characterizes the deprotonated state of any mediating molecule. This pathway is distinct and is rarely considered in the discussion of proton transfer processes. Using a calibrated quantum mechanical/molecular mechanical (QM/MM) model and an effective sampling technique, we study proton transfers in two solution systems and in Carbonic Anhydrase II. Although the relative weight of the “proton hole” and Grotthuss mechanisms in a specific system is difficult to determine precisely using any computational approach, the current study establishes an energetics motivated framework that hinges on the donor/acceptor pK(a) values and electrostatics due to the environment to argue that the “proton hole” transfer is likely as important as the classical Grotthuss mechanism for proton transport in many complex molecular systems