1,721,056 research outputs found
Unveiling the Reaction Machinery of the [Au I ]-Catalyzed Synthesis of Substituted Acenes by a [1,5]-H Shift Cascade Reaction
No full textC-CN vs C-H activation: Actual mechanism of the reaction between [(dippe)PtH]2 and benzonitrile evidenced by a DFT computational investigation
No full textIn this paper we have carried out a DFT computational investigation on the reaction of [(dippe)]PtH](2) (1b) with benzonitrile (PhCN) leading to the products (dippe)Pt(H)(2-C6H4CN) (2) and (dippe)Pt(Ph)CN (5), which formally result from benzonitrile C-H and C-CN activation, respectively. Actually, DFT results indicate a process following a stepwise mechanism that satisfactorily explains the experimental evidence. 5 is a very stable species (19.1 kcal mol(-1) below reactants and significantly more stable than compound 2). Computations clearly show that 5 does not represent an intermediate of the process eventually leading to the final products (dippe)Pt(H)CN (3) and (dippe)Pt(CN)(C6H4CN) (4). The favored path leading to product 3 originates directly from 1b, which is in equilibrium with the adduct 2. The highest energy transition state that must be overcome to give 3 is 29.1 kcal mol(-1) above the reactants. Surmounting this transition structure can be considered a feasible task at the working temperature of 140 degrees C. Product 3 can be obtained only when a second PhCN molecule is involved in the process. PhCN behaves like a hydrogen carrier: it provides the hydrogen finally bonded to platinum in 3 and contributes to form a benzene molecule, which is released in the course of the reaction, as experimentally observed. This PhCN molecule can be considered as a catalyst of the process. Its involvement explains why, when 2 is heated in the absence of PhCN, no reaction is observed. Only in the presence of PhCN can 1b, which is in equilibrium with 2, complete the process to give 3
New Model for a Theoretical Density Functional Theory Investigation of the Mechanism of the Carbonic Anhydrase: How Does the Internal Bicarbonate Rearrangement Occur?
No full textExploring Membrane Cholesterol Binding to the CB1 Receptor: A Computational Perspective
No full textCholesterol (CHOL) is a potential allosteric modulator of the CB1 receptor. In this work, we use atomistic molecular dynamics simulations to study how CHOL interacts with CB1 and to identify its binding sites (BS) and residence times on specific receptor zones. Our results evince minimal changes in CB1 conformational dynamics and secondary structure due to CHOL. We report five BSs, three of which coincide with previously described interaction regions (BS1, BS2, and BS3), while BS4 and BS5 are proposed as new BSs. Quantum descriptors of bonding such as Natural Bond Orbitals (NBO), Quantum Theory of Atoms in Molecules (QTAIM), and Noncovalent Interactions (NCI) analyses are employed to characterize the CHOL-BS interactions. The results show an exponential correlation between the strength of the interactions (mainly hydrogen bonds and hydrophobic contacts) and the residence time at the BSs. Although other approaches exist to identify high-affinity protein sites, our methodology integrates classical and quantum descriptions to better characterize BSs and predict ligand residence times in CB1, distinguishing persistent from transitory contacts. Since CHOL has been suggested as a potential endogenous allosteric ligand, our flexible strategy allows studying interactions that stabilize CHOL in CB1, could be extended to cannabinoid binding, and contribute to designing improved receptor ligands
Unveiling the Reaction Machinery of the [AuI]-Catalyzed Synthesis of Substituted Acenes by a [1,5]-H Shift Cascade Reaction
No full textThe reaction mechanism of the gold-catalyzed synthesis of functionalized acenes via cascade [3,3]-oxo migration/[1,5]-H shift is documented by DFT calculations. Interestingly, the overall reaction machinery displays a notable exothermic profile and the pivotal role played by the metal center in the initial [1,3]-acyloxy migration of 1 was also discovered. Contrarily, contribution of the gold complex in the H shift was negligible as the energy profiles of the gold-based and metal-free protocols are very similar in the latest stage
A mechanistic insights into manganese-catalyzed oxidative homocoupling reactions of Grignard reagents: A computational DFT investigation
No full textWe have carried out a DFT computational investigation on the mechanism of the manganese-catalyzed homocoupling reaction of aryl Grignard reagents RMgX using atmospheric oxygen as an oxidant. The oxidative addition gives an oxo-complex MnR2O2 where the oxygen molecule is η2-bonded to the metal. The free energy barrier for the subsequent reductive elimination (key-step of the cycle) is 9.4 kcal mol-1 when R = p-anisyl, which indicates a rather fast reduction step. A comparative analysis of various systems (R = p-anisyl, o- and p-nitrophenyl, pentafluorophenyl, mesityl, naphtyl and phenylethynyl) suggests that, in general, the kinetics of the reductive elimination step is the result of a complex interplay between electronic and steric effects and, in the case of aryl groups, strongly depends on the nature of the substituent and its position on the phenyl ring. The reduction is favored when the electron density on the coupling carbons is large enough to interact with the metal and form the intermediate oxo-complex. However it cannot be so large to prevent the coupling because of a too strong electron repulsion or too strong Mn-R bonds
DFT Mechanistic Investigation of the Gold(I)-Catalyzed Synthesis of Azepino[1,2-a]indoles
No full textWe describe a computational DFT investigation on the mecha- nism of the one-pot synthesis of azepino-indoles catalyzed by [Au(IPr)Cl]/AgOTf (IPr = 1,3-bis(2,6-diisopropylphenyl-imidazol- 2-ylidene) by the simultaneous construction of the pyrrolyl and seven-membered rings. The mechanism of the final ring-clos- ing event is elucidated, which reveals the counterion-assisted
nucleophilic trapping of the carbonyl moiety by the alkenyl- gold species formed in situ. The computational evidence sup- ports the labeling control experiments and highlights the pres- ence of a cyclopropyl-gold-carbenoid intermediate in the final intramolecular 1,3-hydrogen-shift/skeleton-rearrangement se- quence
Estudio computacional de la polimerización de [épsilon]-caprolactona catalizada / iniciada por derivados de bis(dimetilpirazol)Cu(II) y Zn(II)
No full textEn este trabajo se realizó el estudio computacional para la iniciación de la polimerización de la epsilon-caprolactona por complejos de Cu(II) y Zn(II) con ligandos dimetilpirazol y benzoatos usando DFT. Se estudiaron tres posibles mecanismos y se determinó que el mecanismo más favorecido es aquel en donde ocurre la coordinación de una caprolactona seguido de un ataque nucleofílico del benzoato y una posterior apertura del anillo de la caprolactona. Este ultimo pasó resultó ser el paso determinante de la reacción. Al estudiar el sistema con una única caprolactona, los cálculos indican que el zinc y el cobre tienen actividad similar. Sin embargo, los cálculos con dos caprolactonas sugieren que el zinc posee mayor actividad como iniciador de la polimerizaciónIn this work, the computational study of the initiation mechanism in the polymerization of the epsilon-caprolactone by bis-dimethylpyrazole dibenzoate Copper(II) and by bis-dimethylpyrazole dibenzoate Zinc(II) by DFT. Three possible mechanisms were studied. The most favorable mechanism that in which the caprolactone was coordinated to the metal center, followed by a nucleophilic attack by a benzoate. The final step was the opening of the caprolactone ring, which was also found to be the determining step of the reaction. The study with one caprolactone indicate that both metal have similar activity. However, the mechanistic study with two caprolactones suggest that zinc is more active as the initiator of the polymerizationQuímicoPregrad
Estudio computacional de reacciones pseudo multicomponente para la síntesis de imidazoles trisustituidos
No full textLos imidazoles trisustituidos presentan un gran potencial como agente biológico donde se resalta su papel como anticancerígeno debido a la inhibición de procesos relacionados con topoisomerasas y adicionalmente como antifúngico, donde se encuentran compuestos comerciales como el Econazol y el Miconazol. Desafortunadamente la síntesis de estos compuestos presenta múltiples problemas operacionales relacionados con el uso de condiciones fuertes de reacción y varias etapas. Recientemente el Dr. Jaime Portilla de la Universidad de Andes, junto con sus colaboradores desarrollaron una nueva metodología sintética que incluye alta economía atómica, condiciones de reacción moderadas y fácil operación. Con el fin de estudiar completamente la reacción y las posibilidades que presenta en la producción del imidazol di o trisustituido. Se utilizaron métodos DFT con solvente implícito, con el fin de evaluar el efecto estérico en la amidina utilizada y clarificar la posibilidad de obtener regioisomeros. El estudio logro reproducir los resultados experimentales obtenidos con respecto a los rendimientos y productos obtenidos mediante el calculo de barreras de reacción.Trisubstituted imidazoles have great potential as a biological agent where their role as anticarcinogenic is highlighted due to the inhibition of processes related to topoisomerases and additionally as an anti-fungal, where commercial compounds such as Econazole and Miconazole are found. Unfortunately, the synthesis of these compounds presents multiple operational problems related to the use of strong reaction conditions and various stages. Recently, Dr. Jaime Portilla from the University of Andes, together with his collaborators, developed a new synthetic methodology that includes a high atomic economy, moderate reaction conditions, and easy operation. To study completely, the reaction and the possibilities that it presents in the production of imidazole di or trisubstituted. DFT methods with implicit solvent were used, to evaluate the steric effect in the amidine used and to clarify the possibility of obtaining regioisomers. The study was able to reproduce the experimental results obtained concerning the yields and products obtained by calculating reaction barriers.QuímicoPregrad
Transferencia de acilo de N a O : un estudio computacional
No full text"La ciclación de oxa-Michael es una ruta novedosa para obtener derivados importantes de 1-amino-2,4-dioles. Según estudios computacionales, esta reacción se favorece si se usa un precursor N,N-diacilado (Esquema 2). Sin embargo, cuando se intentó aplicar la anterior estrategia, no ocurrió la conversión esperada, sino una transferencia de acilo del N al O en posición beta (Esquema 4). Incluso, esta reacción sucede en ausencia de solvente y base, en el tubo de resonancia magnética nuclear. Estudiar el mecanismo de esta reacción secundaria es de interés para encontrar cómo favorecer la ciclación de oxa-Michael y, también, para llenar un vacío en la literatura, porque hasta el momento no hay reportes sobre transferencias de acilo en el sentido nitrógeno a oxígeno. Así pues, en este trabajo se reporta un estudio computacional, basado en la teoría del funcional de densidad, sobre el mecanismo de la inesperada transferencia de acilo, de forma intramolecular. Como resultados, se encontró que cuando se considera el efecto del solvente y la base, el primer paso del mecanismo es el determinante. Sin embargo, cuando no se consideran ni el solvente ni la base, el segundo paso del mecanismo resulta el determinante. Por último, se encontró que el mecanismo intramolecular de transferencia de acilo es energéticamente desfavorecido frente a la ciclación de oxa-Michael. Por lo tanto, se requiere estudiar una segunda ruta como la transferencia intermolecular de acilo y se deben incluir los efectos del solvente y la base de la reacción para resultados concluyentes empleando métodos computacionales."--Tomado del Formato de Documento de Grado."The oxa-Michael cyclization is a novel strategy to obtain important 1-amino-2,4-diols derivatives (Scheme 2). According to computational studies, if the process is done using a N,N-diacylated compound, the reaction is favored. However, when this method was tried, the expected product did not appear. Instead, what did occur was an acyl transfer from N to the O in beta position (Scheme 4). In fact, this reaction also happened without solvent and base, inside nuclear magnetic resonance tube. Studying this side reaction is important to know how to promote oxa-Michael cyclization and to fill a gap in literature, because, up to date, there is no article about acyl transfer directed from N to O. Herein, we report a computational study, based on density functional theory, about an intramolecular acyl transfer mechanism of the reaction just mentioned. As results, we found that when solvent and base are considered, the first step is the rate determining one. On the contrary, when solvent and base are neglected, the second step becomes the rate determining one. Finally, we obtained that the intramolecular acyl transfer path is energetically disfavored in comparison to the oxa-Michael cyclization. Therefore, another mechanism such as an intermolecular acyl transference shall be studied, and the effects of the solvent and base should be included to obtain conclusive results using computational tools."--Tomado del Formato de Documento de Grado.QuímicoPregrad
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