Dynamic Approach to Synthetic Lectin for Glucose with Boosted Binding Affinity through C−H Hydrogen Bonds

Abstract

A biomimetic receptor for glucose has been developed with high affinity and selectivity. The receptor was efficiently synthesized in three steps through dynamic imine chemistry followed by imine‐to‐amide oxidation. The receptor features two parallel durene panels, forming a hydrophobic pocket for [CH⋅⋅⋅π] interactions, and two pyridinium residues directing four amide bonds towards the pocket. These pyridinium residues not only improve solubility but also provide polarized C−H bonds for hydrogen bonding. Experimental data and DFT calculations show that these polarized C−H bonds significantly enhance substrate binding. These findings demonstrate the power of dynamic covalent chemistry for creating molecular receptors and using polarized C−H bonds for boosted carbohydrate recognition in water, providing a foundation for developing glucose‐responsive materials and sensors.

Enzyme-like Acyl Transfer Catalysis in a Bifunctional Organic Cage

“…61 oxidatively trap imine assemblies as amide cages in situ, extended cage postfunctionalization methodologies developed by Mastalerz, 55,62,63 which are gaining popularity for accessing functional organic cages. 64 We now report a bifunctional robust organic cage (Figure 1d) that realizes well-characterized enzyme-like acyl-transfer catalysis 65−71 contingent on precisely oriented functional groups and an acyl carrier in a fashion reminiscent of the ping-pong mechanism observed in some proteases and transferases (Figure 1a). 1,72,73 We present NMR analysis and kinetic, crystallographic, and modeling data demonstrating the enzyme-like nature of the process, 53 including substratesaturation kinetics, enthalpic stabilization of the transition state, and the role of covalent nucleophilic catalysis.…”

“…The cavities must also contain suitable endohedral functionalization , to direct substrates or otherwise be restricted to unspecific hydrophobic confinement or proximity-based catalysis or incremental effects that result from enhanced fragment performance. , In our efforts to design stable, soluble organic cages with internal functionality, we recently reported the synthesis of robust amide-linked organic cages featuring a pair of endohedral antipodal carboxylic acids that resemble aspartyl proteases and glycoside hydrolases (like lysozyme) . This work, in which we oxidatively trap imine assemblies as amide cages in situ , extended cage postfunctionalization methodologies developed by Mastalerz, ,, which are gaining popularity for accessing functional organic cages …”

A High‐Affinity “Synthavidin” Receptor for Squaraine Dyes

“…Moreover, recently reported advances in the structure of the bridging isophthalamides should provide additional ways of enhancing binding stability via stabilizing bridgehead interactions. [31]…”

A High‐Affinity “Synthavidin” Receptor for Squaraine Dyes

“…The synthetic sequence in Scheme 1 should allow the preparation of analogues through variations on catechol 5 , so there is broad scope for tuning the system towards even stronger binding. Moreover, recently reported advances in the structure of the bridging isophthalamides should provide additional ways of enhancing binding stability via stabilizing bridgehead interactions [31] …”