Evidence for the Importance of Polarizability in Biomimetic Catalysis Involving Cyclophane Receptors

Ngola, Sarah M.; Dougherty, Dennis A.

doi:10.1021/jo960521y

Cited by 43 publications

(38 citation statements)

References 14 publications

(29 reference statements)

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“…8b) (56). This postulate is substantiated by evidence that the stabilization of the cationic transition state through cation-interactions accelerates catalysis of biomimetic methylation reactions (58,59). Moreover, this is consistent with the proposed interaction of the AdoMet molecule with the conserved motif IV region, which is rich in aromatic residues (Fig.…”

Section: Discussionsupporting

confidence: 76%

Mapping and Molecular Modeling ofS-Adenosyl-l-methionine Binding Sites inN-Methyltransferase Domains of the Multifunctional Polypeptide Cyclosporin Synthetase

Velkov

Lawen

2003

Journal of Biological Chemistry

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We employed a highly specific photoaffinity labeling procedure, using 14 The modified sequence regions correspond to the motif II consensus sequence element, which is involved in directly complexing the adenine and ribose components of AdoMet. We conclude that the AdoMet binding to nonribosomal peptide synthetase N-methyltransferase domains obeys the consensus cofactor interactions seen among most structurally characterized low molecular weight AdoMet-dependent methyltransferases.

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Section: Discussionsupporting

confidence: 76%

Mapping and Molecular Modeling ofS-Adenosyl-l-methionine Binding Sites inN-Methyltransferase Domains of the Multifunctional Polypeptide Cyclosporin Synthetase

Velkov

Lawen

2003

Journal of Biological Chemistry

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“…7). Because these two molecular properties dictate the strength of the electrostatic and dispersion components of the cation-π interaction, these correlations offer further support for the view that stabilizing cation-π interactions are a principal determinant of enantioselectivity in these transformations (35,47,48).…”

Section: Discussionmentioning

confidence: 76%

Attractive noncovalent interactions in asymmetric catalysis: Links between enzymes and small molecule catalysts

Knowles

Jacobsen

2010

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

685

436

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Catalysis by neutral, organic, small molecules capable of binding and activating substrates solely via noncovalent interactions-particularly H-bonding-has emerged as an important approach in organocatalysis. The mechanisms by which such small molecule catalysts induce high enantioselectivity may be quite different from those used by catalysts that rely on covalent interactions with substrates. Attractive noncovalent interactions are weaker, less distance dependent, less directional, and more affected by entropy than covalent interactions. However, the conformational constraint required for high stereoinduction may be achieved, in principle, if multiple noncovalent attractive interactions are operating in concert. This perspective will outline some recent efforts to elucidate the cooperative mechanisms responsible for stereoinduction in highly enantioselective reactions promoted by noncovalent catalysts.enantioselectivity | H bonding | organocatalysis | transition state stabilization

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“…In 34E4, the polarizable aromatic side chain of Trp L91 is potentially well suited to mediate such interactions. However, the small catalytic benefit provided by dispersion forces in diverse model systems (9,17,40) suggests that their contribution to the overall efficiency of 34E4 is relatively minor.…”

Section: Discussionmentioning

confidence: 99%

Structural origins of efficient proton abstraction from carbon by a catalytic antibody

Debler

Ito

Seebeck

et al. 2005

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

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Antibody 34E4 catalyzes the conversion of benzisoxazoles to salicylonitriles with high rates and multiple turnovers. The crystal structure of its complex with the benzimidazolium hapten at 2.5-Å resolution shows that a combination of hydrogen bonding, stacking, and van der Waals interactions is exploited to position both the base, Glu H50 , and the substrate for efficient proton transfer. Suboptimal placement of the catalytic carboxylate, as observed in the 2.8-Å structure of the Glu H50 Asp variant, results in substantially reduced catalytic efficiency. In addition to imposing high positional order on the transition state, the antibody pocket provides a highly structured microenvironment for the reaction in which the carboxylate base is activated through partial desolvation, and the highly polarizable transition state is stabilized by dispersion interactions with the aromatic residue Trp L91 and solvation of the leaving group oxygen by external water. The enzyme-like efficiency of general base catalysis in this system directly reflects the original hapten design, in which a charged guanidinium moiety was strategically used to elicit an accurately positioned functional group in an appropriate reaction environment and suggests that even larger catalytic effects may be achievable by extending this approach to the induction of acidbase pairs capable of bifunctional catalysis.crystal structure ͉ base catalysis ͉ proton transfer ͉ medium effects ͉ orientation effects P roton abstraction from carbon constitutes a fundamental process catalyzed by numerous enzymes, including isomerases, epimerases, racemases, lyases, and some synthases (1). Although heterolytic COH bond cleavage is a kinetically and thermodynamically demanding reaction, deprotonation catalysts rank among the most efficient enzymes known. For example, triosephosphate isomerase, ketosteroid isomerase, and fumarase operate at the diffusion limit (2). The mechanisms by which proteins that contain only weak acids and bases accelerate proton transfers by such enormous factors has long intrigued biochemists (3). Crystal structures and biochemical experiments of such enzymes have highlighted the importance of precisely positioned functional groups with optimized pK a s (3-5), but the precise origins of their high activities remain controversial (6).Valuable insight into the factors that contribute to efficient proton abstraction can be gained from the base-promoted Kemp elimination (1 3 3, Fig. 1), a widely used model system that is sensitive to base strength and solvent environment (7-9). This reaction is also susceptible to catalysis by antibodies (10, 11), albumins (12-14), polyethyleneimine ''synzymes'' (15, 16), organic hosts (17), cationic vesicles (18), and even natural coals (19). Antibody 34E4, which was raised against the cationic 2-aminobenzimidazolium derivative 4, is particularly effective in this regard (11). It promotes the decomposition of benzisoxazole 1 with Ͼ10 3 turnovers per active site and achieves a rate acceleration of 10 6 over backgrou...

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Evidence for the Importance of Polarizability in Biomimetic Catalysis Involving Cyclophane Receptors

Cited by 43 publications

References 14 publications

Mapping and Molecular Modeling ofS-Adenosyl-l-methionine Binding Sites inN-Methyltransferase Domains of the Multifunctional Polypeptide Cyclosporin Synthetase

Mapping and Molecular Modeling ofS-Adenosyl-l-methionine Binding Sites inN-Methyltransferase Domains of the Multifunctional Polypeptide Cyclosporin Synthetase

Attractive noncovalent interactions in asymmetric catalysis: Links between enzymes and small molecule catalysts

Structural origins of efficient proton abstraction from carbon by a catalytic antibody

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