Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion

Abstract

We prepared dual-cavity basket 1 to carry six (S)-alanine residues at the entrance of its two juxtaposed cavities (289 Å(3)). With the assistance of (1)H NMR spectroscopy and calorimetry, we found that 1 could trap a single molecule of 4 (K1 = 1.45 ± 0.40 × 10(4) M(-1), ITC), akin in size (241 Å(3)) and polar characteristics to nerve agent VX (289 Å(3)). The results of density functional theory calculations (DFT, M06-2X/6-31G*) and experiments ((1)H NMR spectroscopy) suggest that the negative homotropic allosterism arises from the guest forming C-H···π contacts with all three of the aromatic walls of the occupied basket's cavity. In response, the other cavity increases its size and turns rigid to prevent the formation of the ternary complex. A smaller guest 6 (180 Å(3)), akin in size and polar characteristics to soman (186 Å(3)), was also found to bind to dual-cavity 1, although giving both binary [1⊂6] and ternary [1⊂62] complexes (K1 = 7910 M(-1) and K2 = 2374 M(-1), (1)H NMR spectroscopy). In this case, the computational and experimental ((1)H NMR spectroscopy) results suggest that only two aromatic walls of the occupied basket's cavity form C-H···π contacts with the guest to render the singly occupied host flexible enough to undergo additional structural changes necessary for receiving another guest molecule. The structural adaptivity of dual-cavity baskets of type 1 is unique and important for designing multivalent hosts capable of effectively sequestering targeted guests in an allosteric manner to give stable supramolecular polymers.

A Hexavalent Basket for Bottom‐Up Construction of Functional Soft Materials and Polyvalent Drugs through a “Click” Reaction

“…[24] Following,p alladium-catalyzed cyclotrimerization of 3 was optimized [24] to give dual-cavity 4 in circa 50 % yield. [30] The procedurei sl abour-intensive with 5g of compound 2 giving 0.4 go fd ual-cavity 4 (Figure2B). It takes about ten weeks for an experienced chemist to complete the synthesis, with the process necessitating costly reagents, copious amounts of organic solvents, and tedious purification steps commonly resulting in the loss of product.…”

“…We hypothesized that "clicking" various substrates (b-d-glucopyranosyl azide is shown) to hexa-alkyne 1,u sing Cu I catalyzed alkyne-azidec ycloaddition (CuAAC), should give structurallyunique,h exavalent,a nd allosteric hosts (see ref. [30]). cene could, perhaps, be optimized [34] to yield the desired dibenzobarrelene.…”

Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015

“…In an interesting study, allostery was mimicked using a dual‐cavity basket that had six alanine residues at the entrance of two juxtaposed cavities that was designed to trap organophosphorus nerve agents . Molecular dynamic simulation and hydrogen‐1 nuclear magnetic resonance spectroscopy suggested a negative homotropic cooperativity of binding in water.…”

A Dynamic Hydrogen‐Bonded Azo‐Macrocycle for Precisely Photo‐Controlled Molecular Encapsulation and Release

“…Manipulation of molecular encapsulation and release has long been an active research subject that engenders wide interests from chemists in mimicking the reversible binding processes of biomolecules and proteins in nature. [1] The design of av ariety of well-defined artificial host systems ensues from this activity,p articularly those associated with implementation of allosteric control [2] in response to external stimuli. [3] Of various stimuli, utilization of light for controlling guest encapsulation presents extraordinary advantages in that it enables fast response and remote control over guest uptake and release.…”