Dezhi Jiao

Triply Triggered Doxorubicin Release From Supramolecular Nanocontainers

The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers.

Supramolecular Peptide Amphiphile Vesicles through Host–Guest Complexation†

Single-tail peptide amphiphiles, have been explored as a new class of biomaterials in many fields including nanotechnology and tissue engineering. A typical peptide amphiphile molecule is linked through a covalent amide bond between a hydrophilic peptide sequence and a hydrophobic lipid of variable length. In an aqueous environment, these peptide amphiphiles undergo self-assembly into structures such as vesicles, both spherical and cylindrical micelles or nanotubes, and have been successfully applied in the biomedical sciences for biomaterial conjugation and as bioactive scaffolds for tissue engineering. Although covalent attachment of two components to form peptide amphiphiles has been extremely successful, the synthetic versatility and the ability to respond to external triggers remains limited. A supramolecular approach to form the peptide amphiphile by connecting two building blocks through a non-covalent interaction would represent a major advance, especially in designing stimuliresponsive systems capable of being targeted by specific triggers. Cucurbit[n]urils (CB[n]) are a family of macrocyclic hosts known to form inclusion complexes with selectivity and high binding affinity in aqueous media. One of the larger macrocycles in this family, CB[8], can be used as a “molecular handcuff” to join two molecules together in a non-covalent fashion, and has been applied to form biomaterials such as polymer–protein conjugation and protein dimerization. Additionally, CB[n] hosts have found great utility in “switch on/switch off” fluorescence assays by supramolecular complexation with various fluorescent guests. Pyrene and its derivatives have been widely used as fluorescence probes in a large number of complex systems, on account of their high fluorescence quantum yields, long excited state lifetimes and the ability to form excimers. Herein, we utilize a functional pyrene bearing an imidazolium group both as a fluorescence sensor and as a guest for CB[8] and linked it to a simple peptide sequence (1). Pyrene-functionalized peptide 1 is able to form the supramolecular peptide amphiphile complex 3 with viologen lipid 2 through CB[8] conjugation, as shown in Figure 1a. During the

A Systems Approach to Controlling Supramolecular Architecture and Emergent Solution Properties via Host−Guest Complexation in Water

The assembly behavior of aryl/alkyl imidazolium ionic liquid salts in aqueous solution has been investigated. These salts undergo self-assembly into one-dimensional stacks via hydrophobic and π-π interactions upon increasing concentration, which led to a substantial increase in the solution viscosity in water. Addition of the macrocyclic host molecules cucurbit[n]urils (CB[n]) were found to effectively alter the supramolecular assemblies, as evidenced from the dramatic increase (by CB[7]) and decrease (by CB[8]) in solution viscosity and aggregation size in water, on account of the different binding stoichiometries, 1:1 complexation with CB[7] and 2:1 complexation with CB[8]. Furthermore, the aggregate architectures were controllably modified by competitive guests for the CB[n] hosts. This complex supramolecular systems approach has tremendous implications in the fields of molecular sensor design, nonlinear viscosity modification, and controlled release of target molecules from a defined supramolecular scaffold in water.

Peptide separation through a CB[8]-mediated supramolecular trap-and-release process.

We demonstrate a supramolecular peptide separation approach by the selective immobilization of peptides bearing an N-terminal tryptophan onto a CB[8]-modified gold substrate, followed by electrochemical release. The CB[8]-stabilized heteroternary complexes were characterized by (1)H NMR, ESI-MS, UV/vis, and fluorescence spectroscopy and cyclic voltammetry. Micropatterned CB[8]-modified gold substrates were found to trap only the recognizable N-tryptophan-containing peptides from a peptide mixture that could be visualized as green peptide arrays under fluorescence microscopy. Subsequently, the bound peptides were released from the modified substrates by the controlled single-electron reduction of viologen. The fully reversible trap-and-release process was repeated for 13 cycles, and the cumulative release profile of the dye-peptide conjugate was monitored by fluorescence spectroscopy, indicating that no degradation occurred.

Size Selective Supramolecular Cages from Aryl-Bisimidazolium Derivatives and Cucurbit[8]uril

A series of bisimidazolium salts were synthesized as novel guests for the macrocyclic host molecule cucurbit[8]uril (CB[8]). These bisimidazolium-CB[8] binary complexes exhibited a unique cage structure with the imidazolium rings acting as lids, leading to a size-dependent binding selectivity by altering the hydrophobic linker between the two imidazolium moieties. This new class of CB[8] complexes was also capable of binding small solvent molecules, including acetone, acetonitrile, diethyl ether, and tetrahydrofuran (THF) in an aqueous environment.

An Aqueous Supramolecular side-chain polymer: Designed for Molecular Loading

Hydrophilic copolymers containing recognition motifs based on 2-naphthol moieties in their side chains for the self-assembly with cucurbit[8]uril (CB[8]), have been prepared by reversible addition–fragmentation chain transfer polymerization. Self-assembly of the copolymer with both redox sensitive hydrophilic and hydrophobic viologen derivatives in the presence of CB[8] has been investigated.

Isolation of cucurbit[n]uril homologues with imidazolium salts in a recyclable manner

A method for isolating cucurbit[n]uril (CB[n]) homologues (CB[5–8]) has been developed by utilising several selective imidazolium salts. Complexation with CB[7] and CB[8] causes a dramatic increase in their solubility in water, allowing for facile separation of CB[5] and CB[6] from their corresponding mixtures. The larger homologues (CB[7] and CB[8]) can then be isolated as pure, uncomplexed macrocycles via a solid state metathesis (SSM) ion exchange reaction. Moreover, the imidazolium salts can be readily recycled after CB[n] purification, leading to a near-quantitative recovery loop and providing a “green” isolation process. This methodology remarkably increases the isolated yields of each of the major CB[n] components, reduces the time required for purification, and is amenable to scale-up, which would represent a significant improvement in the field of macrocycles.