Theoretical Studies On The Mechanism Of Chemical Reactions Within The Molecular Containers

Molecular container is the molecule or molecular assembly constructed via covalent or noncovalent interactions with special internal cavities.It can selectively recognize and bind a variety of guests through noncovalent interactions.The inner phase of molecular containers is very different from that of the bulk surroundings.The included guests are greatly affected by specific steric conditions and arrangement of functional groups in the cavity.These unique microenvironments and nano-structures ultimately ensure their bright application future in many important areas such as modulating reactions,stabilizing active intermediates and selectively recognition.In recent years,a number of important molecular containers have been synthesized and their catalytic efficiency have been experimentally measured.But the mechanistic details of these reactions catalyzed by molecular containers are still lacking.It is well known that computational chemistry can make significant contribution to the understanding of various chemical reactions.However,because of high computational cost,theoretical investigations on organic reactions assisted by molecular containers are still limited,although some studies based on molecular mechanics(MM)calculations or hybrid quantum mechanics/molecular mechanics(QM/MM)calculations have been reported.In this thesis,our aim is to understand the molecular mechanisms of several chemical reactions within the molecular containers by using accurate quantum chemistry calculations.Our investigation focuses on the favorable reaction pathways and the influence of the guest-host interactions on the reactivity of the encapsulated reactions.Main contributions of the present work can be summarized as follows:1.In chapter 3,we investigate the mechanism for the reaction between a primary amine and a cavitand with an introverted aldehyde group with density functional theory calculations.The reaction involves two stages:1)the nucleophilic addition of the primary amine to the aldehyde group forms the hemiaminal;2)the dehydration of the hemiaminal to form the imine.Our calculations show the nucleophilic addition in the cavity is favored because the host-guest interaction between the cavitand and the substrate provides a driving force for forming the association complex and stabilizing the transition state.The hemiaminal intermediate is mainly stabilized by strong hydrogen bonds between the hemiaminal and the cavitand's wall.The dehydration of the hemiaminal to produce imine is catalyzed by the amide NH group on the cavitand's wall.Firstly,the amide NH group transfers a proton to the hydroxyl group of the hemiaminal,forming a water molecule to be eliminated.Then,the deprotonated amide group will take a proton back from the NH group of the iminium ion to restore the cavitand.In some sense,the studied cavitand with an introverted aldehyde group resembles an enzyme active site.2.In chapter 4,we combine Monte Carlo simulations and density functional theory calculations to study the mechanism of the Diels-Alder reaction of p-quinone and cyclohexadiene catalyzed by a self-assembled molecular capsule.In the first step,Monte Carlo simulations are employed to search for several low-energy conformers of various guest-host association complexes.Then stationary points on several pathways within the capsule are obtained with full system density functional theory calculations.Our calculations show that the encapsulation of the reactants into the cage is driven by hydrogen bonding interaction and ?-? stacking interaction between two reactants and the capsule.The encapsulated Diels-Alder reaction at different locations inside the capsule may have quite different reactivity,due to different guest-host interactions.A comparison of the free energy profiles of the Diels-Alder reaction in the capsule and in the bulk solution reveals that the Diels-Alder reaction in the capsule is accelerated because the host-guest interaction leads to a relatively smaller barrier for the cycloaddition.The present study indicates that the rate of a chemical reaction may be noticeably modulated by the guest-host interaction between the substrate and the container.3.In chapter 5,we elucidate the mechanism of the methylation reaction within a dimethylaminopyridine(DAMP)-modified meta-phenyleneethynylene(mPE)foldamer,with three methyl sulfonate esters with different alkyl groups selected as methylating agents.Unlike traditional supramolecular reactors,foldamer is the oligomer that folds into a conformationally ordered state stabilized by noncovalent interactions between nonadjacent monomer units.By comparing the Gibbs free energy profiles of the methylation reactions in the foldamer and in the reference compound,we find that the noncovalent interactions between the foldamer and the substrate,such as hydrogen bonds and van der Waals interactions,stabilize the transition state,resulting in the acceleration of the confined reaction.As the substrate's alkyl chain increases,the guest-host interaction becomes stronger,enhancing the methylation rates.Our present calculations can provide satisfactory explanations on known experimental facts.