While self-assembly is a super star in current chemistry, supramolecular disassembly process can also give a sensational show. I would like to pick out some attractive programs here.

One of the most famous approaches to achieve self-assembly is to play with amphiphilic molecules, including block copolymers and low-moleculelar-weight surfactants. The structural unit of these molecules in their supramolecular architectures is generally called micelles. Despite their variety in morphologies including spheres, fibrils, tubes and vesicles, the driving force is unexceptionally the aggregation of the sovatophobic parts of more than one amphiphilic molecules in a certain solvent, and their stabilization by the sovatophilic parts of these molecules. In the simplest and widest case, the solvent is water (thus changing the prefix sovato- into hydro-). By incorporating stimuli-sensitive functional groups with the hydrophilic or -phobic parts of the molecules, their amphiphilicity would be eliminated by environment condition changes (e.g. making them totally hydrophilic), and the micelles disassembled into unimers – a molecularly dissolved state. Disassembly of micelles can be multi-stimuli responsive:

Temperature:
Poly(N-isopropyl acrylaimde) (PNIPAAm) seems to have dissipated all chemists’ ideas of thermosensitive structures. A well-known water-soluble (hydrophilic) polymer showing a Lower-Critical-Solution-Temperature (LCST) at about 30.9C, above which the polymer becomes insoluble (hydrophopic) and phase separates, PNIPAAm is widely grafted on all kinds of molecules or surfaces where it never fails to show its thermosensitivity although at different LCSTs. AB-type block copolymer consisting PNIPAAm segment and a hydrophilic segment is amphiphilic and forms micelles in water below its LCST. Reversing the temperature makes the copolymer total amphiphilic and the micelle disassemble. The most simple example is PEG-b-PNIPAAm diblock copolymer micelle in water (Macromol. Rapid Commun. 2001, 22, 1390-1393). One of the practical usage of these kind of micelles is drug delivery system (DDS) for tumor. After administration and arrival of the micelles at the tumor, a burst of a loaded drug could be achieved by local hypothermia.

pH:
The first thing to come into most chemists’ minds when they think of pH sensitivity is polyelectrolytes, that is, polyacids and polybases which are charged in a certain range of pH and electrostatically repel, leading to certain pH sensitive behaviors according to different supramolecular architectures. But in terms of assembling and disassembling a micelle, polyelectrolytes are not ‘schizophrenic’ enough to cause substantial discrepancy in hydrophilicity. So actually people choose another strategy – pH induced cleavage of chemical bonds. Cyclic benzylidene acetals, for instance, contain acid sensitive linkages whose rate of hydrolysis is generally proportional to [H+] and is expected to increase 250-fold as the pH is changed from 7.4 to 5.0. This rate can be further manipulated by introducing substituents to the aromatic ring. A polymer chain with cyclic benzylidene acetal side groups is thus hydrophobic in neutral to basic environment due to the benzyl groups, and becomes hydrophilic at acidic environment after hydrolysis, due to the hydrolytic product – charged carboxylic acid groups which are hydrophilic and repel each other (Chem. Commun. 2003, 1640-1641). Therefore, a copolymer micelle containing this kind of chain can be thermo-disassembled at low pH values. However, this kind of disassembly can hardly called a ‘supramolecular’ one, being neither non-covalent nor reversible.

Light:
Similar to the case of pH-response disassembly described above, there are few examples of light-induced disassembly of micelles in the real supramolecular sense. The only one I can find is a successful trial using a azobenzene-containing surfactant. Azobenzene undergoes reversible trans-cis photoisomerization under UV-light irradiation, meanwhile changing its polarity. A “photo-switchable” azobenzene-modified cationic surfactant is found able to undergo reversible vesicle formation/disruption, as evidenced under transmission electron microscopic (TEM) observation (J. Phys. Chem. B 1999, 103, 10737-10740).

Oxidation:
Ferrocene moiety typifies the oxidation which leads to non-covalent (i.e. supramolecular) consequences. In the Fe(II) state, ferrocene dissolves readily in hydrocarbon solvents such as hexanes, and is relatively non-polar. When it is one-electron oxidized, the blue, relatively stable ferricenium cations is formed. An alkylferrocene may thus be oxidized to an amphiphilic structure. Reversible micellization of ferrocene containing surfactants was achieved by redox switching (J. Am. Chem. Soc. 1985, 107, 6865) .

Host-guest interactions:
I believe the most exciting part of suparmolecular chemistry should be the various host-guest interactions. One of the most versatile kind of host molecules is cyclodextrins (mostly in alpha-, beta- and gamma-forms). They can not only include small guest molecules into their cavities but also long-chain polymers, to form a supramolecule called inclusion complex. The two earliest confirmed cyclodextrin/polymer host-guest pairs are alpha-cyclodextrin/poly(ethylene glycol) (PEG) and beta-cyclodextrin/poly(propylene glycol) (PPG). It is also known that PPG-PEG-PPG triblock copolymer (Pluronic) forms micelles in water, PPG being the hydrophobic core and PEG the hydrophilic corona. Adding a derivative of beta-cyclodextrin into the aqueous solution of micellized copolymer ruptures the micelles due to favored inclusion complex between beta-cyclodextrin and the core-forming PPG block (Langmuir 2007, 23, 460-466).

DNA:

[Image from the website of Dr. Andreas Herrmann’s group in Max-Planck-Institute for Polymer Research]

In terms of supramolecular chemistry, DNA represents the feature of well-defined building block with its ease of sequence design and amplification, as well as the concept of molecular recognition by its base-pair coupling rules. In terms of polymer science, DNA is a polyelectrolyte (polybase), and is therefore a hydrophilic chain. It is interesting to block-copolymerize a single-strand DNA (ssDNA) with common synthetic polymers and watch the spherical micelles formed in water, where the ssDNA chains serve as corona. If the ssDNA chains are of the same sequence, adding another ‘template’ ssDNA with the complementary sequence may induce the forming of double helix within the corona. More interestingly, if the ‘template’ ssDNA contains five repeating complementary sequence, one template can form double helix with the ssDNA segments of five block copolymers, thus the double helix cannot form without affecting the corona structure of the micelle. Instead, the spherical micelles are disassemble and converted into rod-like ones (Angew. Chem. Int. Ed. 2007, 46, 1172-1175).

Non-Amphiphilic Strategy:
We have talked too much about micelles, where disassembly is mostly achieved by affecting the core or corona structure of the micelle. Host-guest chemistry provides us a new strategy, competitive guest. For example, alpha-cyclodextrin (again) forms inclusion complex with the alkyl side chain of the dodecyl-modified poly(acrylic acid) in water, converting the solution into a gel. Adding a photoresponsive competitive guest molecule containing an azobenzene group, the alpha-cyclodextrin include more favorably the competitive guest in its trans confromation, leaving the alkyl side chain of the polymer ‘naked’, and the gel changed back into fluid (sol). When irradiated with UV-light, the azobenzene guest molecule undergoes photoisomerization and the cis conformation predominates, which is unfavroable, if not impossible, for alpha-cyclodextrin to include, so the host molecule returns to its old lover, dodecyl chain of the polymer, and cause the sol-to-gel transition again. Visible light can render the azobenzene guest molecule ‘adorable’ again by recovering their conformation into trans, and you know what alpha-cyclodextrin is going to do this time. Therefore by adding a photoresponsive competitive guest, a supramolecular system can undergo photoresponsive (dis)assembly reversibly.

Surely my literature collection is limited so please leave you comment if you are also interested in supramolecular self-assembly.