Catalytic Strategies Within the Confined Spaces of Coordination Cages

Abstract

Coordination cages have emerged as an interesting and diverse subset of supramolecular systems that utilise the assembly of ligands and metals to create constructs with hollow interiors. This inner space provides opportunities for many applications; however, exploiting it for catalysis is arguably the most interesting and challenging of academic pursuits. In this chapter, we will outline how coordination cage catalysis emerged and followed on from earlier examples of supramolecular methods and highlight the remarkable progress that has been made in the past two decades. This chapter is not intended as a comprehensive review; rather it has been limited to select examples that serve to represent both what has been achieved and what is the current state of the art.

Enzyme-like Acyl Transfer Catalysis in a Bifunctional Organic Cage

“…Early work in enzyme mimicry tended to rely on arduous multistep synthesis to install functional groups near binding cavities to enhance rates of reaction by increasing effective molarities. ,− In contrast, dynamically self-assembled cages (covalent) and capsules (noncovalent) are easier to access but are either restricted to mild catalysis conditions that do not cause them to disassemble or must undergo a postsynthetic locking procedure to render them stable, a process scarcely available for noncovalent assemblies . 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 …”

“… 12 , 52 − 54 In contrast, dynamically self-assembled cages (covalent) and capsules (noncovalent) are easier to access but are either restricted to mild catalysis conditions that do not cause them to disassemble or must undergo a postsynthetic locking procedure 55 to render them stable, a process scarcely available for noncovalent assemblies. 56 The cavities must also contain suitable endohedral functionalization 51 , 57 to direct substrates or otherwise be restricted to unspecific hydrophobic confinement or proximity-based catalysis 58 or incremental effects that result from enhanced fragment performance. 48 , 59 In our efforts to design stable, soluble organic cages with internal functionality, we recently reported 60 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).…”

Enzyme-like Acyl Transfer Catalysis in a Bifunctional Organic Cage

“…55 Nitschke describes the difficulties in postassembly modification of non-covalently assembled cages. 56 The cavities must also contain suitable endohedral functionalization 51,57 to direct substrates, or otherwise be restricted to unspecific hydrophobic confinement or proximity-based catalysis, 58 or incremental effects that result from enhanced fragment performance. 48,59 The majority of "binding site" macrocyclic enzyme model work has utilised the hydrophobic effect to increase reaction rates on a bound substrate.…”

“…57 Lusby discusses many of the origins of /approaches to catalysis. 58 Some cages take advantage of an enhanced version of the reactivity of the monomers: The authors of a cage-based photocatalysis paper state: 59 "With the help of cage based photocatalyst and within a short time of ca. 15.0 min, >99% benzylamine molecules have been converted into N-benzylidenebenzylamine (based on the NMR data; Table 2).…”