Generation of Multicomponent Molecular Cages using Simultaneous Dynamic Covalent Reactions

Abstract

Cage compounds are very attractive structures for a wide range of applications and there is ongoing interest in finding effective ways to access such kinds of complex structures, particularly those possessing dynamic adaptive features. Here we report the accessible synthesis of new type of organic cage architectures, possessing two different dynamic bonds within one structure: hydrazones and disulfides. Implementation of three distinct functional groups (thiols, aldehydes and hydrazides) in the structure of two simple building blocks resulted in their spontaneous and selective self-assembly into aromatic cage-type architectures. These organic cages contain up to ten components linked together by twelve reversible covalent bonds. The advantage provided by the presented approach is that these cage structures can adaptively self-sort from a complex virtual mixture of polymers or macrocycles and that dynamic covalent chemistry enables their deliberate disassembly through controlled component exchange.

Tuning the Solubility of Self-Assembled Fluorescent Aromatic Cages Using Functionalized Amino Acid Building Blocks

“…Both types of building blocks must have functional groups that allow facile formation of reversible covalent bonds such as acyl-hydrazones and disulfides. The TPE aldehyde (TPE-Ald) was retained as the aromatic core of the cage-like structures, because we wanted our new cages to have an analogous structure to those reported previously (Drozdz et al, 2017). We decided to use the amino group in cysteine hydrazide to insert a structural extension via amide bond formation.…”

“…HR-MS analyses were carried out at the Laboratoire de Mesures Physiques, IBMM, Université de Montpellier using Micromass Q-Tof instruments. The TPE aldehyde (TPE-Ald) and Fmoc- L -Cys-STr-Hyd-Boc ( 2 ) were obtained according to the previously reported method (Drozdz et al, 2017).…”

“…Recently, we have reported a method for obtaining a new type of molecular cage-like system using a set of two orthogonal reversible reactions (disulfides and acyl-hydrazones) that occur simultaneously (Drozdz et al, 2017). This was the first report of multi-dynamic and multi-component cages selectively obtained in a one-pot process, and characterized in semi-aqueous media, by applying two distinct reversible covalent bonds.…”

Dynamic Covalent Chemistry as a Facile Route to Unusual Main‐Group Thiolate Assemblies and Disulfide Hoops and Cages

“…1d). [21] Incorporating three different functional groups (thiols, aldehydes, and hydrazides) in two building blocks leads to strongly fluorescent hydrazone-and disulfide-based tripodal and tetrapodal aromatic cage-type architectures. While it is possible for various polymeric, macrocyclic, and cage constituents to be expressed in the system, only the cages form, predominantly due to favorable π-π stacking and hydrogen bonds.…”

A tetrahedral molecular cage with a responsive vertex

“…The ability to ‘turn-on’ a subset of dynamic functionalities affords a synthetic handle to reversibly shift product distributions and generate modified structures through post-synthetic transformations 30–32. The utility of orthogonal DCC has also been applied to the synthesis of organic cages and macrocycles through both simultaneous and sequential activation of orthogonal bonds to generate complex architectures from simple precursors 33–38. Recent success by our lab and others in the synthesis of organic cages via alkyne metathesis has led us to pursue both synthetic modifications and materials applications of these shape-persistent structures (Fig.…”