Supramolecular Catalysis of Orthoformate Hydrolysis in Basic Solution: An Enzyme-Like Mechanism

Pluth, Michael D.; Bergman, Robert G.; Raymond, Kenneth N.

doi:10.1021/ja802839v

Cited by 94 publications

(64 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…41,42 Monitoring the reaction by 1 H NMR revealed the production of both ethanol and formate anion. Addition of NEt 4 + , a strongly binding guest, inhibited the catalysis and confirmed the catalytic importance of 1.…”

Section: Acid Catalysis In Basic Solutionmentioning

confidence: 99%

Proton-Mediated Chemistry and Catalysis in a Self-Assembled Supramolecular Host

2009

Self Cite

View full text Add to dashboard Cite

Synthetic supramolecular assemblies able to encapsulate guest molecules often impart unique reactivity on the encapsulated guests. Although much less complex than the active sites of enzymes, synthetic host molecules have been developed that can carry out complex reactions within their cavities.Over the last decade, the Raymond group has developed a series of self-assembled supramolecules able to encapsulate small guest molecules. This Account details recent collaborative work between the Raymond and Bergman groups focusing on chemical catalysis stemming from the encapsulation of protonated guests and expanding to acid-catalysis in basic solution.We initially investigated the ability of a self-assembled supramolecular host molecule to encapsulate protonated guests. Our study of encapsulated protonated amines revealed a rich array of host-guest chemistry. Guest exchange studies established that the rates of encapsulated protonated amines were dependent on the steric bulk of the amine rather than its basicity. The purely-rotational T symmetry of the host molecule effectively desymmetrized the geminal N-methyl groups and allowed for the observation and quantification of the barriers for nitrogen inversion followed by bond rotation. In further screening of amine guests, small nitrogen heterocycles such as N-alkylaziridines, -azetidines and -pyrrolidines were found to be encapsulated as proton-bound homodimers or homotrimers. Expanding 3 the study of protonated amines to investigate the thermodynamic stabilization of protonated amines showed that encapsulation makes the encapsulated amines more basic and raises the effective basicity of the protonated amines by up to 4.5 pK a units.The thermodynamic stabilization of protonated guests was translated into chemical catalysis by applying the stabilization of protonated species to reactions proceeding through monocationic protonated intermediates. Orthoformates, which are generally stable in neutral or basic solution, were found to be suitable substrates for catalytic hydrolysis by the assembly. Orthoformates small enough to undergo encapsulation were readily hydrolyzed by the assembly in basic solution with observed rate accelerations of up to 3900 when compared to the uncatalyzed reaction. Furthering the analogy to enzymes that obey Michaelis-Menten kinetics, competitive inhibition was demonstrated with the inhibitor NPr 4 + , thereby confirming that the interior cavity of the assembly was the active site for catalysis. Mechanistic studies revealed that the assembly is intimately required for catalysis and that the rate limiting step of the reaction is proton-transfer from hydronium to the encapsulated substrate.Encapsulation in the assembly changes the orthoformate hydrolysis mechanism from an A-1, in which decomposition of the protonated substrate is the rate limiting step, to an A-S E 2 mechanism in which proton transfer is the rate limiting step. The study of hydrolysis reactions in the assembly was next extended to acetals, which were also catalytically hydrolyzed ...

show abstract

Section: Acid Catalysis In Basic Solutionmentioning

confidence: 99%

Proton-Mediated Chemistry and Catalysis in a Self-Assembled Supramolecular Host

2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Raymond tetrahedral capsule 12 can be constructed from a variety of (apical) metal ions, and has be shown to be a consummate controller of size-and shape-selective catalysis [37,40,127,131,132]. It has also been shown to possess unusual memory properties [133] and can stabilize reactive intermediates [134].…”

Section: Common Classes Of Water-soluble Hostsmentioning

confidence: 99%

Van Der Waals Interactions and the Hydrophobic Effect

Gibb

2011

Chemosensors

View full text Add to dashboard Cite

“…We have previously shown through kinetic analysis that water, in either its neutral or protonated form, can enter 1, so the enthalpy of the hydrogen bond formed between a protonated amine and water molecule ([B⅐⅐H⅐⅐OH 2 ] ϩ ) was also calculated (21,31). The geometry optimized structures for the [B⅐⅐H⅐⅐B] ϩ and [B⅐⅐H⅐⅐OH 2 ] ϩ complexes are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In our exploration of encapsulated protonated guests, we have shown that protonation can allow for encapsulation of amine guests and also that chelating amines are able to intramolecularly share 1 proton to allow for observation of the nitrogen inversion bond rotation process (NIR) inside of the assembly (17). We have used the thermodynamic stabilization of protonated guests in 1 to demonstrate that acid-catalyzed hydrolyses of acetals and orthoformates can be carried out in basic solution inside of 1 (18)(19)(20)(21). Herein, we expand on the ability of 1 to encapsulate protonated substrates in the simultaneous encapsulation of multiple cyclic amines as proton-bound homodimers and also present an example of heterodimer and homotrimer formation.…”

mentioning

confidence: 99%

Encapsulation and characterization of proton-bound amine homodimers in a water-soluble, self-assembled supramolecular host

Pluth

Fiedler

Mugridge

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Cyclic amines can be encapsulated in a water-soluble selfassembled supramolecular host upon protonation. The hydrogenbonding ability of the cyclic amines, as well as the reduced degrees of rotational freedom, allows for the formation of proton-bound homodimers inside of the assembly that are otherwise not observable in aqueous solution. The generality of homodimer formation was explored with small N-alkyl aziridines, azetidines, pyrrolidines, and piperidines. Proton-bound homodimer formation is observed for N-alkylaziridines (R ‫؍‬ methyl, isopropyl, tert-butyl), Nalkylazetidines (R ‫؍‬ isopropyl, tert-butyl), and N-methylpyrrolidine. At high concentration, formation of a proton-bound homotrimer is observed in the case of N-methylaziridine. The homodimers stay intact inside the assembly over a large concentration range, thereby suggesting cooperative encapsulation. Both G3(MP2)B3 and G3B3 calculations of the proton-bound homodimers were used to investigate the enthalpy of the hydrogen bond in the protonbound homodimers and suggest that the enthalpic gain upon formation of the proton-bound homodimers may drive guest encapsulation.host-guest chemistry ͉ molecular recognition ͉ guest encapsulation ͉ amine protonation H ydrogen bonding and protonation play vital roles in both chemical and biological phenomena as one of the most prevalent intermolecular forces in nature (1-4). Although hydrogen bonding is often viewed as a weak interaction, the strength of a special class of strong hydrogen bonds, often referred to as ionic hydrogen bonds, can range from 5 to 35 kcal/mol (5). These strong hydrogen bonds are important in nucleation, self-assembly, protein folding, reactivity of enzyme active sites, formation of membranes in biological systems, and biomolecular recognition (5-7). Because of the importance of hydrogen bonding in so many aspects of chemical and biological systems, a number of synthetic and theoretical studies have examined their magnitude and origin (8, 9). Many of the computational studies have focused on simple proton-bound homodimers and heterodimers, where 2 neutral bases are bound by 1 proton (Fig. 1), because experimental energies for these complexes can be obtained from gas phase thermochemical studies such as variable-temperature high-pressure mass spectrometry (5).In simple hydrogen-bonded complexes such as those shown in Fig. 1, the hydrogen bond strength is maximized when the proton donor and the conjugate base of the proton acceptor have similar proton affinities. Therefore, the strongest hydrogen bonds are formed when the 2 basic components, minus the proton, are identical (5). Although the proton-bound homodimers and heterodimers can be observed in the gas phase, solution studies of these types of complexes remain rare. To the best of our knowledge, proton-bound homodimers or heterodimers predominantly form in aprotic organic solvents, rather than protic hydrogen-bonding solvents (5, 10).Previous work in the K.N.R. group has explored the formation, guest exchange dynamics, and mediated reac...

show abstract

Supramolecular Catalysis of Orthoformate Hydrolysis in Basic Solution: An Enzyme-Like Mechanism

Cited by 94 publications

References 94 publications

Proton-Mediated Chemistry and Catalysis in a Self-Assembled Supramolecular Host

Proton-Mediated Chemistry and Catalysis in a Self-Assembled Supramolecular Host

Van Der Waals Interactions and the Hydrophobic Effect

Encapsulation and characterization of proton-bound amine homodimers in a water-soluble, self-assembled supramolecular host

Contact Info

Product

Resources

About