No, Not That Way, the Other Way: Creating Active Sites in Self-Assembled Host Molecules

Abstract

This Account describes our efforts over the last decade to synthesize self-assembled metal–ligand cage complexes that display reactive functional groups on their interiors. This journey has taken us down a variety of research avenues, including studying the mechanism of reversible self-assembly, analyzing ligand self-sorting properties, post-assembly reactivity, molecular recognition, and binding studies, and finally reactivity and catalysis. Each of these individual topics are discussed here, as are the lessons learned along the way and the future research outlook. These self-assembled hosts are the closest mimics of enzymes to date, as they are capable of size- and shape-selective molecular recognition, substrate activation and turnover, as well as showing less common ‘biomimetic’ properties such as the ability to employ cofactors in reactivity, and alter the prevailing mechanism of the catalyzed reactions.1 Introduction2 Paddlewheels and Self-Sorting Behavior3 First-Row Transition-Metal-Mediated Assembly: Sorting and Stereochemical Control4 Post-Assembly Reactivity5 Molecular Recognition and Catalysis6 Conclusions and Outlook

Supramolecular Capsule-Catalyzed Highly β-Selective Furanosylation Independent of the SN1/SN2 Reaction Pathway

“…Supramolecular capsule and cage catalysis has started emerging as a novel tool for tackling current synthetic challenges in organic chemistry. − Recent examples − included the site-selective functionalization of terpenes, regioselective spirocyclization, asymmetric hydroformylation, selective reductions, , enantioselective aza-Darzens reaction, tail-to-head terpene cyclizations, and a short synthesis of a complex sesquiterpene natural product . Our group recently reported the β-selective pyranosylation of readily available α-pyranosyl chlorides and fluorides (Figure A) catalyzed inside the supramolecular resorcin[4]­arene capsule I (Figure B) .…”

Exploiting reduced-symmetry ligands with pyridyl and imidazole donors to construct a second-generation stimuli-responsive heterobimetallic [PdPtL4]4+ cage

“…[3][4][5][6][7][8][9][10][11][12][13] There are now many approaches that enable the straightforward generation of these high-symmetry metallo-architectures from simple building blocks. The resulting materials have been exploited for a range of applications, including encapsulation, [14][15][16] separations, 17 catalysis, [18][19][20][21] environmental remediation, 22 and biological activity. 23,24 While these are important applications and the results are impressive they almost universally exploit the cavities of the MSAs in a dissimilar way to active sites in enzymes.…”

A Water‐ and Base‐Stable Iminopyridine‐Based Cage That Can Bind Larger Organic Anions

“…Potential applications range from chemical transport or separation [1–11] and molecular sensing [12–17] to the stabilization of reactive guests [18–27] . Moreover, catalysis has also been a major focus in self‐assembled molecular capsules and cages [28–49] . Out of the reactions catalysed most examples feature cationic intermediates and transition states.…”