Computer simulation of reactions in β-cyclodextrin molecular reactors: transition state recognition

Abstract

Cyclodextrins have attracted much interest in recent years because of their potential use as molecular reactors allowing organic reactions in aqueous solution. To better understand their effect on reaction mechanisms, we have carried out a computational study of a prototypical process (neutral ester hydrolysis) in a beta-cyclodextrin (beta-CD). Two models have been used for the reactor. The first and simpler one assumes that the medium can be described by a polarizable dielectric continuum. The second one takes into account the discrete nature of the beta-CD and water molecules thanks to a computational approach that combines the use of Quantum Mechanics, Molecular Mechanics and Molecular Dynamics techniques. We focus on neutral pH processes for which either acceleration or inhibition has experimentally been observed depending on ester derivatives. Our calculations rationalize such observations by showing that the two reaction mechanisms usually invoked for hydrolysis, stepwise (involving two transitions states with formation of a -C(OH)(2)OR tetrahedral intermediate) and concerted, undergo opposite effects in the beta-CD environment. The results highlight the role played by molecular shape recognition. Thus, in spite of a higher polarity exhibited by the three transition states with respect to the reactants, the interactions with the beta-CD cavity may either increase or decrease the activation barrier due to different 3D-arrangements of the chemical structures.

Modeling Solvation in Supercritical CO2

“…First, it is necessary to unravel the effect of the thermodynamic conditions both on the solubility and on the host-guest complex formation before envisagingm ore intensivea pplications of complexation. Moreover,o nce this goal is attained, the possibility of using the macromolecular cavity as am icroreactor,a sh as been achieved for similar systems in aqueous solution, [199] would be worth investigating.…”

“…First, it is necessary to unravel the effect of the thermodynamic conditions both on the solubility and on the host-guest complex formation before envisagingm ore intensivea pplications of complexation. Moreover,o nce this goal is attained, the possibility of using the macromolecular cavity as am icroreactor,a sh as been achieved for similar systems in aqueous solution, [199] would be worth investigating. Supercriticalc arbon dioxide has been successfully used at the same time as ar eactant and as olvation medium for the phosphine imide reaction, allowing the replacement of organic compounds commonly used in the synthesis of ureas to avoid the use of toxic reactants such as phosgene and isocyanates.…”

Theoretical study of the inclusion complexation of TCDD with cucurbit[n]urils

“…59 Applications to mimic host-guest interactions have also been envisaged in recent years. 60,61 However, it should be kept in mind that implicit solvent models can become questionable in some cases, such as systems with strong solvent-solute interactions and strong solvent coordination of ionic species. 62 The present CBn-TCDD systems involve only nonspecic interactions between the solvent and solute, which are expected to be able to be described by implicit solvent models.…”

Formation of Reactant Complex Structure for Initiation Reaction of Lactone Ring-Opening Polymerization by Cooperation of Multiple Cyclodextrin

“…In this work, as a first step toward understanding the polymerization process of polyester initiated by CDs, we investigated the initiation reaction mechanism of δ-valerolactone (VL) ring-opening polymerization by β-CD with the 15 The transition state recognition mechanism of the ester hydrolysis reaction in a β-CD was also investigated by quantum mechanical (QM) and MD calculations. 16 Here we chose the polymerization process of VL initiated by β-CD because this combination exhibited an efficient polymerization result and was most thoroughly investigated by the experiments. 9,10 On the basis of the experimental findings, we assumed that the reactant VL has to satisfy the following three conditions for the initiation reaction.…”

“…For example, Ruiz-López et al reported an atomistic mechanism of how CDs can distinguish chiral molecules by quantum mechanical/molecular mechanical (QM/MM) simulations. , Lawtrakul et al investigated the behavior of included solvent molecules and host CDs by molecular dynamics (MD) simulations . The transition state recognition mechanism of the ester hydrolysis reaction in a β-CD was also investigated by quantum mechanical (QM) and MD calculations …”