- Supramolecular chemistry
Supramolecular chemistry refers to the area of
chemistrythat focuses on the noncovalent bondinginteractions of molecules. [cite journal | author=Lehn JM | title=Supramolecular chemistry | journal=Science | volume=260 | issue=5115 | year=1993 | pages=1762–3 | pmid=8511582 | doi=10.1126/science.8511582] [Supramolecular Chemistry, J.-M. Lehn, Wiley-VCH (1995) ISBN-13:978-3527293117] While traditional chemistry focuses on the covalent bond, supramolecular chemistry examines the weaker and reversible noncovalent interactions between molecules. These forces include hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, pi-pi interactions and electrostaticeffects. Important concepts that have been demonstrated by supramolecular chemistry include molecular self-assembly, folding, molecular recognition, host-guest chemistry, mechanically-interlocked molecular architectures, and dynamic covalent chemistry. [cite journal | author=Gennady V. Oshovsky, Dr. Dr., David N. Reinhoudt, Prof. Dr. Ir., Willem Verboom, Dr. | title=Supramolecular Chemistry in Water | journal= Angewandte Chemie International Edition| volume=46 | issue=14 | year=2007 | pages=2366–2393 | doi=10.1002/anie.200602815] The study of non-covalent interactions is crucial to understanding many biological processes from cell structure to vision that rely on these forces for structure and function. Biological systems are often the inspiration for supramolecular research.
The existence of intermolecular forces was first postulated by
Johannes Diderik van der Waalsin 1873. However, it is with Nobel laureate Hermann Emil Fischerthat supramolecular chemistry has its philosophical roots. In 1890, Fischer suggested that enzyme-substrate interactions take the form of a "lock and key", pre-empting the concepts of molecular recognitionand host-guest chemistry. In the early twentieth century noncovalent bonds were understood in gradually more detail, with the hydrogen bond being described by Latimer and Rodebush in 1920.
The use of these principles led to an increasing understanding of
protein structureand other biological processes. For instance, the important breakthrough that allowed the elucidation of the double helical structure of DNAoccurred when it was realized that there are two separate strands of nucleotides connected through hydrogen bonds. The use of noncovalent bonds is essential to replication because they allow the strands to be separated and used to template new double stranded DNA. Concomitantly, chemists began to recognize and study synthetic structures based on noncovalent interactions, such as micelles and microemulsions.
Eventually, chemists were able to take these concepts and apply them to synthetic systems. The breakthrough came in the 1960s with the synthesis of the
crown ethers by Charles J. Pedersen. Following this work, other researchers such as Donald J. Cram, Jean-Marie Lehnand Fritz Vogtlebecame active in synthesizing shape- and ion-selective receptors, and throughout the 1980s research in the area gathered a rapid pace with concepts such as mechanically-interlocked molecular architectures emerging.
The importance of supramolecular chemistry was established by the 1987
Nobel Prizefor Chemistry which was awarded to Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen in recognition of their work in this area. ["Chemistry and Physics Nobels Hail Discoveries on Life and Superconductors; Three Share Prize for Synthesis of Vital Enzymes" Harold M. Schmeck Jr. "New York Times" October 15, 1987 [http://query.nytimes.com/gst/fullpage.html?res=9B0DE0DB143DF936A25753C1A961948260&sec=&spon=&partner=permalink&exprod=permalink] ] The development of selective "host-guest" complexes in particular, in which a host molecule recognizes and selectively binds a certain guest, was cited as an important contribution.
In the 1990s, supramolecular chemistry became even more sophisticated, with researchers such as
James Fraser Stoddartdeveloping molecular machineryand highly complex self-assembled structures, and Itamar Willnerdeveloping sensors and methods of electronic and biological interfacing. During this period, electrochemical and photochemical motifs became integrated into supramolecular systems in order to increase functionality, research into synthetic self-replicating system began, and work on molecular information processing devices began. The emerging science of nanotechnologyalso had a strong influence on the subject, with building blocks such as fullerenes, nanoparticles, and dendrimers becoming involved in synthetic systems.
Control of supramolecular chemistry
Supramolecular chemistry deals with subtle interactions, and consequently control over the processes involved can require great precision. In particular, noncovalent bonds have low energies and often no
activation energyfor formation. As demonstrated by the Arrhenius equation, this means that, unlike in covalent bond-forming chemistry, the rate of bond formation is not increased at higher temperatures. In fact, chemical equilibriumequations show that the low bond energy results in a shift towards the breaking of supramolecular complexes at higher temperatures.
However, low temperatures can also be problematic to supramolecular processes. Supramolecular chemistry can require molecules to distort into thermodynamically disfavored
conformations (e.g. during the "slipping" synthesis of rotaxanes), and may include some covalent chemistry that goes along with the supramolecular. In addition, the dynamic nature of supramolecular chemistry is utilized in many systems (e.g. molecular mechanics), and cooling the system would slow these processes.
thermodynamicsis an important tool to design, control, and study supramolecular chemistry. Perhaps the most striking example is that of warm-blooded biological systems, which cease to operate entirely outside a very narrow temperature range.
The molecular environment around a supramolecular system is also of prime importance to its operation and stability. Many solvents have strong hydrogen bonding, electrostatic, and charge-transfer capabilities, and are therefore able to become involved in complex equilibria with the system, even breaking complexes completely. For this reason, the choice of solvent can be critical.
Concepts in supramolecular chemistry
Molecular self-assemblyis the construction of systems without guidance or management from an outside source (other than to provide a suitable environment). The molecules are directed to assemble through noncovalent interactions. Self-assembly may be subdivided into intermolecular self-assembly (to form a supramolecular assembly), and intramolecular self-assembly (or folding as demonstrated by foldamersand polypeptides). Molecular self-assembly also allows the construction of larger structures such as micelles, membranes, vesicles, liquid crystals, and is important to crystal engineering.
Molecular recognition and complexation
Molecular recognitionis the specific binding of a guest molecule to a complementary host molecule to form a host-guest complex. Often, the definition of which species is the "host" and which is the "guest" is arbitrary. The molecules are able to identify each other using noncovalent interactions. Key applications of this field are the construction of molecular sensors and catalysis.
Molecular recognition and self-assembly may be used with reactive species in order to pre-organize a system for a chemical reaction (to form one or more covalent bonds). It may be considered a special case of supramolecular
catalysis. Noncovalent bonds between the reactants and a "template" hold the reactive sites of the reactants close together, facilitating the desired chemistry. This technique is particularly useful for situations where the desired reaction conformation is thermodynamically or kinetically unlikely, such as in the preparation of large macrocycles. This pre-organization also serves purposes such as minimizing side reactions, lowering the activation energyof the reaction, and producing desired stereochemistry. After the reaction has taken place, the template may remain in place, be forcibly removed, or may be "automatically" decomplexed on account of the different recognition properties of the reaction product. The template may be as simple as a single metal ion or may be extremely complex.
Mechanically-interlocked molecular architectures
Mechanically-interlocked molecular architecturesconsist of molecules that are linked only as a consequence of their topology. Some noncovalent interactions may exist between the different components (often those that were utilized in the construction of the system), but covalent bonds do not. Supramolecular chemistry, and template-directed synthesis in particular, is key to the efficient synthesis of the compounds. Examples of mechanically-interlocked molecular architectures include catenanes, rotaxanes, molecular knots, and molecular Borromean rings.
Dynamic covalent chemistry
dynamic covalent chemistrycovalent bonds are broken and formed in a reversible reaction under thermodynamic control. While covalent bonds are key to the process the system is directed by noncovalent forces to form the lowest energy structures.
Many synthetic supramolecular systems are designed to copy functions of biological systems. These
biomimeticarchitectures can be used to learn about both the biological model and the synthetic implementation. Examples include photoelectrochemical systems, catalytic systems, protein designand self-replication.
Molecular imprintingdescribes a process by which a host is constructed from small molecules using a suitable molecular species as a template. After construction, the template is removed leaving only the host. The template for host construction may be subtly different from the guest that the finished host bind. In its simplest form, imprinting utilizes only stericinteractions, but more complex systems also incorporate hydrogen bonding and other interactions to improve binding strength and specificity.
Molecular machines are molecules or molecular assemblies that can perform functions such as linear or rotational movement, switching, and entrapment. These devices exist at the boundary between supramolecular chemistry and nanotechnology, and prototypes have been demonstrated using supramolecular concepts.
Building blocks of supramolecular chemistry
Supramolecular systems are rarely designed from first principles. Rather, chemists have a range of well-studied structural and functional building blocks that they are able to use to build up larger functional architectures. Many of these exist as whole families of similar units, from which the analog with the exact desired properties can be chosen.
ynthetic recognition motifs
* The pi-pi charge-transfer interactions of
bipyridiniumwith dioxyarenes or diaminoarenes have been used extensively for the construction of mechanically interlocked systems and in crystal engineering.
* The use of
crown etherbinding with metal or ammonium cations is ubiquitous in supramolecular chemistry.
* The formation of carboxylic acid dimers and other simple hydrogen bonding interactions.
* The complexation of
bipyridines or tripyridines with ruthenium, silveror other metal ions is of great utility in the construction of complex architectures of many individual molecules.
* The complexation of
porphyrins or phthalocyanines around metal ions gives access to catalytic, photochemical and electrochemical properties as well as complexation. These units are used a great deal by nature.
Macrocycles are very useful in supramolecular chemistry, as they provide whole cavities that can completely surround guest molecules and may be chemically modified to fine-tune their properties.
Cyclodextrins, calixarenes, cucurbiturils and crown ethers are readily synthesized in large quantities, and are therefore convenient for use in supramolecular systems.
* More complex
cyclophanes, and cryptands can be synthesized to provide more taliored recognition properties.
Many supramolecular systems require their components to have suitable spacing and conformations relative to each other, and therefore easily-employed structural units are required.
* Commonly used spacers and connecting groups include
polyetherchains, biphenyls and triphenyls, and simple alkyl chains. The chemistry for creating and connecting these units is very well understood.
nanoparticles, nanorods, fullerenesand dendrimersoffer nanometer-sized structure and encapsulation units.
* Surfaces can be used as scaffolds for the construction of complex systems and also for interfacing electrochemical systems with electrodes. Regular surfaces can be used for the construction of
self-assembled monolayers and multilayers.
Photo-/electro-chemically active units
Porphyrins, and phthalocyanines have highly tunable photochemical and electrochemical activity as well as the potential for forming complexes.
Photochromicand photoisomerizablegroups have the ability to change their shapes and properties (including binding properties) upon exposure to light.
* TTF and
quinones have more than one stable oxidation state, and therefore can be switched with redox chemistry or electrochemistry. Other units such as benzidinederivatives, viologens groups and fullerenes, have also been utilized in supramolecular electrochemical devices.
* The extremely strong complexation between
avidinand biotinis instrumental in blood clotting, and has been used as the recognition motif to construct synthetic systems.
* The binding of
enzymeswith their cofactorshas been used as a route to produce modified enzymes, electrically contacted enzymes, and even photoswitchable enzymes.
DNAhas been used both as a structural and as a functional unit in synthetic supramolecular systems.
Supramolecular chemistry and
molecular self-assemblyprocesses in particular have been applied to the development of new materials. Large structures can be readily accessed using bottom-up synthesis as they are composed of small molecules requiring fewer steps to synthesize. Thus most of the bottom-up approaches to nanotechnologyare based on supramolecular chemistry.
A major application of supramolecular chemistry is the design and understanding of
catalysts and catalysis. Noncovalent interactions are extremely important in catalysis, binding reactants into conformations suitable for reaction and lowering the transition state energy of reaction. Template-directed synthesis is a special case of supramolecular catalysis. Encapsulation systems such as micelles and dendrimers are also used in catalysis to create microenvironments suitable for reactions (or steps in reactions) to progress that is not possible to use on a macroscopic scale.
Supramolecular chemistry is also important to the development of new pharmaceutical therapies by understanding the interactions at a drug binding site. The area of
drug deliveryhas also made critical advances as a result of supramolecular chemistry providing encapsulation and targeted release mechanisms. In addition, supramolecular systems have been designed to disrupt protein-protein interactions that are important to cellular function.
Data storage and processing
Supramolecular chemistry has been used to demonstrate computation functions on a molecular scale. In many cases, photonic or chemical signals have been used in these components, but electrical interfacing of these units has also been shown by supramolecular
signal transductiondevices. Data storagehas been accomplished by the use of molecular switches with photochromicand photoisomerizable units, by electrochromicand redox-switchable units, and even by molecular motion. Synthetic molecular logic gates have been demonstrated on a conceptual level. Even full-scale computations have been achieved by semi-synthetic DNA computers.
Research in supramolecular chemistry also has application in
green chemistrywhere reactions have been developed which proceed in the solid state directed by non-covalent bonding. Such procedures are highly desirable since they reduce the need for solvents during the production of chemicals.
Other Devices and Functions
Supramolecular chemistry is often pursued to develop new functions that cannot appear from a single molecule. These functions also include magnetic properties, light responsiveness, self-healing polymers, molecular sensors, etc. Supramolecular research has been applied to develop high-tech sensors, processes to treat radioactive waste, and contrast agents for CAT scans.
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