A Multi-State, Allosterically-Regulated Molecular Receptor With Switchable Selectivity

Abstract

A biomimetic, ion-regulated molecular receptor was synthesized via the Weak-Link Approach (WLA). This structure features both a calix[4]arene moiety which serves as a molecular recognition unit and an activity regulator composed of hemilabile phosphine alkyl thioether ligands (P,S) chelated to a Pt(II) center. The host-guest properties of the ion-regulated receptor were found to be highly dependent upon the coordination of the Pt(II) center, which is controlled through the reversible coordination of small molecule effectors. The environment at the regulatory site dictates the charge and the structural conformation of the entire assembly resulting in three accessible binding configurations: one closed, inactive state and two open, active states. One of the active states, the semiopen state, recognizes a neutral guest molecule, while the other, the fully open state, recognizes a cationic guest molecule. Job plots and (1)H NMR spectroscopy titrations were used to study the formation of these inclusion complexes, the receptor binding modes, and the receptor binding affinities (Ka) in solution. Single crystal X-ray diffraction studies provided insight into the solid-state structures of the receptor when complexed with each guest molecule. The dipole moments and electrostatic potential maps of the structures were generated via DFT calculations at the B97D/LANL2DZ level of theory. Finally, we describe the reversible capture and release of guests by switching the receptor between the closed and semiopen configurations via elemental anion and small molecule effectors.

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

“…Promising allostericm odulation of the receptora ctivity of multi-component 3D containers has been obtained using chemical, [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] redox, [49][50][51] or photoinducedr eactions. [52][53][54][55][56][57][58] Most of such structures are self-assembled through hydrogen or metal-ligand bonds, but covalent structures remaini nteresting for their high chemical stabilitya nd their ability to respond to variouss ignaling events.…”

Sensitive and Specific Guest Recognition through Pyridinium‐Modification in Spindle‐Like Coordination Containers

“…A restricted chemical microenvironment relies on the well‐defined hollow structure built in the coordination containers for guest encapsulation, which leads to a number of applications such as stabilization of highly reactive species, guest recognition, drug delivery, and supramolecular catalysis . Moreover, the coordination containers can provide an accessible functionalization approach based on the building components thus opening up a wider range of new properties and/or functions, for instance, sensing, emission, controllable guest uptake and release . However, limited by complicated and tedious ligand design and synthesis, achieving multiple functionalities based on specific supramolecular containers remains highly challenging despite the tremendous progress in this research area during the last decades.…”

Anion Receptor Chemistry

“…Potential diagnostic and therapeutic applications of Zn 2 BDPA-functionalized fluorescence probes and liposomes were proposed.Molecular receptors that mimic the allosteric regulation of substrate binding in biological proteins are of interest. Mendez-Arroyo et al39 demonstrated an elegantly designed system in which anion binding to a metal center in a calix[4]arene-based receptor could control guest binding to the cavity of the receptor. A hemilabile Pt(II) complex was placed above the cavitand and served as the regulatory site by dictating the charge and conformation of the receptor.…”