Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed "cucurbituril" by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants--the pumpkin. In the intervening years, the fundamental binding properties of CB[6]-high affinity, highly selective, and constrictive binding interactions--have been delineated by the pioneering work of the research groups of Mock, Kim, and Buschmann, and has led to their applications in waste-water remediation, as artificial enzymes, and as molecular switches. More recently, the cucurbit[n]uril family has grown to include homologues (CB[5]-CB[10]), derivatives, congeners, and analogues whose sizes span and exceed the range available with the alpha-, beta-, and gamma-cyclodextrins. Their shapes, solubility, and chemical functionality may now be tailored by synthetic chemistry to play a central role in molecular recognition, self-assembly, and nanotechnology. This Review focuses on the synthesis, recognition properties, and applications of these unique macrocycles.

The cucurbit[n]uril family

III. Foldamer Research 3910 A. Overview 3910 B. Motivation 3910 C. Methods 3910 D. General Scope 3912 IV. Peptidomimetic Foldamers 3912 A. The R-Peptide Family 3913 1. Peptoids 3913 2. N,N-Linked Oligoureas 3914 3. Oligopyrrolinones 3915 4. Oxazolidin-2-ones 3916 5. Azatides and Azapeptides 3916 B. The â-Peptide Family 3917 1. â-Peptide Foldamers 3917 2. R-Aminoxy Acids 3937 3. Sulfur-Containing â-Peptide Analogues 3937 4. Hydrazino Peptides 3938 C. The γ-Peptide Family 3938 1. γ-Peptide Foldamers 3938 2. Other Members of the γ-Peptide Family 3941 D. The δ-Peptide Family 3941 1. Alkene-Based δ-Amino Acids 3941 2. Carbopeptoids 3941 V. Single-Stranded Abiotic Foldamers 3944 A. Overview 3944 B. Backbones Utilizing Bipyridine Segments 3944 1. Pyridine−Pyrimidines 3944 2. Pyridine−Pyrimidines with Hydrazal Linkers 3945

A field guide to foldamers.

Water gelation by small organic molecules.

Fluorescence quenching has been used to study the cooperative conformational transition in a series of oligo(phenylene ethynylene)s having tri(ethylene glycol) monomethyl ether side chains. In nonpolar solvents such as chloroform, the intensity of fluorescence emission from the backbone chromophore increases smoothly as the chain lengthens from the dimer through the octadecamer. In polar solvents such as acetonitrile, on the other hand, chains having more than eight units exhibit fluorescence quenching concomitant with the growth of an intramolecular excimer-like band. This observation is consistent with π-stacking of aromatic rings for chains that are long enough to fold back on themselves, driven by solvophobic interactions. Titration experiments in which the solvent composition was gradually changed from pure acetonitrile to pure chloroform showed sigmoidal curves characteristic of a cooperative transition. These data were analyzed using a two-state approximation and a model in which the free energy di...

Cooperative Conformational Transitions in Phenylene Ethynylene Oligomers: Chain-Length Dependence

The ordered solution conformation of a synthetic chain molecule has been used to create a high-affinity binding site for small-molecule guests. The diastereoselective complexation of chiral monoterpenes with an achiral, amphiphilic m-phenylene ethynylene oligomer is demonstrated by induced circular dichroism in polar solvents. The stoichiometry of this solvophobically driven, reversible complex is strictly 1:1. The results are interpreted as a preferential binding of the chiral guest to one of the oligomer's enantiomeric helical conformations. Evidence for binding within the hydrophobic tubular cavity of the helix is provided by studies on modified oligomers.

Foldamer-Based Molecular Recognition

Circular dichroism spectroscopy has been used to study the self-assembly of two series of m-phenylene ethynylene oligomers in highly polar solvents. The helical conformation of shorter oligomer lengths was found to be stabilized in aqueous acetonitrile solutions, while longer oligomers began to interact intermolecularly. The intermolecular aggregation of the oligomers in aqueous solutions revealed a chain length dependent association that required the presence of a stable helical conformation. Evidence for intermolecular interactions is provided by Sergeants and Soldiers experiments in which the twist sense bias of a chiral oligomer is transferred to an achiral oligomer.

Self-assembly of folded m-phenylene ethynylene oligomers into helical columns.

Cooperative interactions among the side chains of the helically folded phenylene-ethynylene oligomer shown (n=2, 4, 6, 8, 10, 12, 14, 16, 18) can induce a twist sense bias. Therefore, the side chains can play more than just an ancillary role in these conformationally ordered oligomers. The onset of the twist sense bias lags significantly behind the appearance of helical conformations, possibly because a large ensemble of "collapsed" conformations is initially formed.

Ryan B. Prince

Papers

A field guide to foldamers.

Cooperative Conformational Transitions in Phenylene Ethynylene Oligomers: Chain-Length Dependence

Foldamer-Based Molecular Recognition

Self-assembly of folded m-phenylene ethynylene oligomers into helical columns.

Twist Sense Bias Induced by Chiral Side Chains in Helically Folded Oligomers.