Natural Order - Supramolecules


December 20, 2002

Vol. 6 Number 51

An Online Research Digest Published Weekly Since 1997

"One of the symptoms of approaching nervous breakdown is the belief that one's work is terribly important."  -- Bertrand Russell (1872-1970)
1. Introduction
2. On Supramolecular Chemistry
3. Supramolecular vs. Traditional Chemistry
4. On Non-Covalent Synthesis
5. Towards Molecular Information-Processing and Self-Organization
6. Self-Assembly: Biological and Chemical Aspects
7. Supramolecular Polymers
8. From Molecules to Materials: Current Trends and Future Directions
9. On Supramolecular Chirality
10. Solid-State NMR and Supramolecular Systems
11. On the Engineering of Supramolecular Crystals
12. On the History of Crystal Engineering
13. On Self-Organizing Supramolecular Porphyrin Arrays
14. On Hydrated Amphiphiles and Supramolecular Materials
15. Molecular and Supramolecular Photoactive Switches
16. Metal-Coordination in Supramolecules
17. Selective Assembly of Supramolecular Aggregates
18. Supramolecules and Biological Movements


From the Editor: As the following excerpt illustrates, supramolecular chemistry is a new chemistry, a chemistry of macromolecular architectures and dynamics, and an exciting new interface between the physical sciences and biology. As with any attempt to sample the work of an entire discipline, many aspects and many researchers are unfortunately not explicitly included. Nobel Laureate Jean-Marie Lehn (Louis Pasteur University, FR) is one of the founders of the field.

"Today's chemists are able to understand and to make practical use of the mutual operations of molecules both natural and synthetic. To do so, they have had to expand their horizons, to see chemistry not just as the science of individual molecules but also as an investigation of how molecules come together and interact in groups -- in pairs, in small aggregates or in vast throngs. This is the business of supramolecular chemistry -- the chemistry beyond the molecule, the study of ensembles of molecules working together. Only by taking a perspective this broad can chemists hope to understand life's molecular complexity. Yet that will be but a by-product of the supramolecular chemist's craft. For this chemistry 'beyond the molecule' is demonstrating that chemistry itself has a vaster potential than any scientist of Erwin Schroedinger's generation would have guessed, a potential whose realization will demand not just technical aptitude but also creative imagination. It is as if the brick-makers have suddenly realized that their products need not be an end in themselves but provide a means for them to become architects...

"Civilization combats entropy through a network of information exchange. (Information was made formally the opposite of entropy in Claude Shannon's information theory in the 1940s.) We talk to each other, we send letters, faxes and electronic mail, we write things down and store them in libraries where others can look them up. We pass on this information from generation to generation -- and, because it comes mixed with a dash of inevitable disorder, it changes slowly in the process. When molecules need to get organized, they adopt analogous strategies. This is why the key concepts of supramolecular chemistry embrace not just those of traditional molecular chemistry -- structure and energy -- but also a third, information. We can regard supramolecular chemistry as a kind of molecular sociology, wherein the behavior of the collective results from the nature of the individuals and the relations among them. The components of supramolecular chemistry communicate, they form associations, they have preferences and aversions, they follow instructions and pass on information. Central to these exchanges is the idea of molecular recognition, whereby one molecule is able to distinguish another by its shape or properties."

J-M. Lehn and P. Ball, in: Nina Hall (ed.): The New Chemistry. Cambridge University Press. 2000. p.300,301.


Gautam R. Desiraju (University of Hyderabad, IN) discusses supramolecular chemistry:

For a long time, chemists have tried to understand nature at a level purely molecular, considering only structures and functions involving strong covalent bonds. But some of the most important biological phenomena do not involve the making and breaking of covalent bonds, the linkages that connect atoms to form molecules, Instead, biological structures are usually made from loose aggregates held together by weak non-covalent interactions. Because of their dynamic nature, these interactions are responsible for most of the processes occurring in living systems. Chemists have been slow to recognize the enormous variety -- in terms of structure, properties, and functions -- offered by this more relaxed approach to making chemical compounds. The slow shift toward this new approach began in 1894, when Emil Fischer (1852-1919) proposed that an enzyme interacts with its substrate as a key does with its lock. This elegant mechanism contains the two main tenets of what would become a new subject, supramolecular chemistry. These two principles are molecular recognition and supramolecular function. The term "supramolecular chemistry" was coined in 1969 by Jean-Marie Lehn in his study of inclusion compounds and cryptands. The award of the 1987 Nobel Prize in Chemistry to Charles Pedersen, Donald Cram, and Lehn signified the formal arrival of the subject on the chemical scene. Lehn defined supramolecular chemistry as "the chemistry of the intermolecular bond". Just as molecules are built by connecting atoms with covalent bonds, supramolecular compounds are built by linking molecules with intermolecular interactions.

Nature 2001 412:397

Related Background:


One has the sense that a renaissance in materials science is underway, a significant refocusing with a potential impact at least as great as that following the introduction of plastics more than a century ago. At a recent materials science symposium on "Materials for the 21st Century and Beyond" (April 29, Hunter College New York, US), seven leading figures in the field presented perspectives on the near future. Nobel Laureate Jean- Marie Lehn (Louis Pasteur University Strasbourg, FR) reviewed the work of his group in designing and creating molecules programmed by virtue of their structure and functional groups to spontaneously organize themselves into larger supramolecular assemblies held together by hydrogen bonds, metal coordination, and so on. The interest is not so much in the mere self-assembly into large structures, but in the fact that such self-assembled structures exhibit a new spectrum of physical and chemical properties with important potential practical applications. Lehn's research involves the use of metal ions to organize and stabilize supramolecular structures with reversible architectures, and such structures have special redox, optical, magnetic and other properties. Michael D. Ward (University of Minnesota Minneapolis, US) reported on the use of molecular building blocks to construct crystalline frameworks with preordained architectures and new functions. Ward's structures involve sheets of organic cations and organic anions hydrogen- bonded to each other in a hexagonal arrays. Work by other groups has involved supramolecular multilayers. In 1988, researchers discovered that when certain films consisting of alternating layers of a magnetic and a non-magnetic metal are placed in a magnetic field, the resistance of the film changes markedly, a phenomenon known as "giant magnetoresistance". This discovery apparently reenergized the magnetic materials science field because of important possible applications to information storage technology, and Stuart P. Parkin (IBM San Jose, US) is now leading a productive research group in this field. Ron Dagani (Chemical and Engineering News), who authors a review of the symposium, concludes: "Parkin's lecture made it clear that, at least in the case of magnetic multilayers, some materials envisioned for the 21st century are already here."

Chem. & Eng. News 1998 8 June.


S.T. Nguyen et al (Northwestern University, US) discuss supramolecular chemistry:

For over 100 years, chemistry has focused primarily on understanding the behavior of molecules and their construction from constituent atoms, and our current level of understanding of molecules and chemical construction techniques has given us the confidence to tackle the construction of virtually any molecule, be it biological or designed, organic or inorganic, monomeric or macromolecular in origin. During the last few decades, chemists have extended their investigations beyond atomic and molecular chemistry into the realm of "supramolecular chemistry". Terms such as "molecular self-assembly", "hierarchical order", and "nanoscience" are often associated with this area of research. In general, supramolecular chemistry is the study of interactions between, rather than within, molecules -- in other words, chemistry using molecules rather than atoms as building blocks. Whereas traditional chemistry deals with the construction of individual molecules (1 to 100 angstroms length scale) from atoms, supramolecular chemistry deals with the construction of organized molecular "arrays" with much larger length scales (1 to 100 nanometers). In classical molecular chemistry, strong association forces such as covalent and ionic bonds are used to assemble atoms into discrete molecules and hold them together. In contrast, the forces used to organize and hold together supramolecular assemblies are weaker non-covalent interactions, such as hydrogen bonding, polar attractions, van der Waals forces, and hydrophilic-hydrophobic interactions.

Proc. Nat. Acad. Sci. 2001 98:11849


D.N. Reinhoudt and M. Crego-Calama (University of Twente, NL) discuss noncovalent synthesis, the authors making the following points:

1) With increasing understanding of the individual interactions that govern the molecular recognition process, the focus is now shifting to supramolecular chemistry as a tool for noncovalent synthesis. Cooperative, weak interactions are used for the spontaneous formation of large aggregates that have well-defined structures (helicates, grids, molecular containers, capsules, cyclic arrays, and the like), in which the individual components are not connected through covalent but through noncovalent bonds.

2) In this emerging field of noncovalent synthesis, one might expand the definition of a molecule to "a collection of atoms held together by covalent and noncovalent bonds." Contrary to the classical definition of a molecule, these supramolecules may be highly dynamic on the human time scale. On the other hand, noncovalent and covalent synthesis are not fundamentally different; both have as the objective to introduce specific connectivities between atoms. The advantage of noncovalent synthesis is that noncovalent bonds are formed spontaneously and reversibly under conditions of thermodynamic equilibrium, with the possibility of error correction and without undesired side products. Furthermore, it does not require chemical reagents or harsh conditions.

3) In biosynthesis, chemical transformations are highly stereoselective with only one of the many possible stereoisomers (compounds with the same molecular formula that differ in the way their atoms are arranged in space) being formed. With the current state of chemical synthesis, a comparable stereocontrol over covalent bond formation is possible for many types of reactions as well. In the synthesis of noncovalent systems, this control over stereochemistry is much more difficult, because bonds between individual components are kinetically labile and are continuously broken and formed. However, in noncovalent synthesis, the stereochemistry of reaction products (regioselectivity, diastereoselectivity, and enantioselectivity) must also be controlled.

4) One of the areas where noncovalent synthesis has a great advantage over covalent synthesis is the bottom-up (chemical) assembly of nanostructures. Large-scale nanometer fabrication will be a requirement for future molecular electronic devices, high-density data storage, or drug delivery. Covalent synthesis has been proven to be extremely fruitful for the synthesis of compounds with molecular weights in the range of 100 to 3000 daltons such as palytoxin, norbrevetoxin, and taxol. Nevertheless, with the exception of the sequential methodologies for the synthesis of biopolymers (or oligomers), there are no simple covalent strategies for the synthesis of pure molecules that have molecular weights between 10^(4) and 10^(6) kilodaltons. Such molecules have dimensions between 3 and 20 nanometers and fill the gap between small molecules and larger nano-objects that are now accessible by top-down (physical) fabrication methods, mainly based on lithography. This is also the size range where quantum confinement influences the electronic and optical properties of matter.

5) In summary: In chemistry, noncovalent interactions are now exploited for the synthesis in solution of large supramolecular aggregates. The aim of these syntheses is not only the creation of a particular structure, but also the introduction of specific chemical functions in these supramolecules.

References (abridged):

1. C. J. Pedersen, Angew. Chem. Int. Ed. 27, 1021 (1988)

2. J.-M. Lehn, Angew. Chem. Int. Ed. 27, 89 (1988)

3. D. J. Cram, Angew. Chem. Int. Ed. 27, 1009 (1988)

4. R. Ungaro, A. Arduini, A. Casnati, A. Pochini, F. Ugozzoli, Pure Appl. Chem. 68, 1213 (1996)

5. P. Wallimann, T. Marti, A. F?rer, F. Diederich, Chem. Rev. 97, 1567 (1997)

Science 2002 295:2403


J-M. Lehn (Louis Pasteur University, FR) discusses perspectives in supramolecular chemistry, the author making the following points:

1) The selective binding of a substrate by a molecular receptor to form a supramolecular species involves molecular recognition which rests on the molecular information stored in the interacting species. The functions of supramolecules cover recognition, as well as catalysis and transport. In combination with polymolecular organization, they open ways towards molecular and supramolecular devices for information processing and signal generation. The development of such devices requires the design of molecular components performing a given function (e.g., photoactive, electroactive, ionoactive, thermoactive, or chemoactive) and suitable for assembly into an organized array.

2) Light-conversion devices and charge-separation centers have been realized with photoactive cryptates formed by receptors containing photosensitive groups. Electroactive and ionoactive devices are required for carrying information via electronic and ionic signals. Redox-active polyolefinic chains, like the "caroviologens", represent molecular wires for electron transfer through membranes. Push-pull polyolefins possess marked nonlinear optical properties. Tubular mesophases, formed by organized stacking of suitable macrocyclic components, as well as "chundle"-type structures, based on bundles of chains grafted onto a macrocyclic support, represent approaches to ion channels. Lipophilic macrocyclic units form Langmuir-Blodgett films that may display molecular recognition at the air-water interface.

3) Supramolecular chemistry has relied on more or less preorganized molecular receptors for effecting molecular recognition, catalysis, and transport processes. A step beyond preorganization consists in the design of systems undergoing self-organization, that is, systems capable of spontaneously generating a well-defined supramolecular architecture by self- assembling from their components under a given set of conditions. Several approaches to self-assembling systems have been pursued: the formation of helical metal complexes, the double-stranded helicates, which result from the spontaneous organization of two linear polybipyridine ligands into a double helix by binding of specific metal ions; the generation of mesophases and liquid crystalline polymers of supramolecular nature from complementary components, amounting to macroscopic expression of molecular recognition; the molecular-recognition-directed formation of ordered solid-state structures.


J.S. Lindsey (Carnegie Mellon University, US) discusses self- assembly, the author making the following points:

1) Molecular electronics places a premium on organized 3- dimensional architectures. Self-assembly has been touted as a solution to the synthesis problems of molecular electronics. Biological self-assembly provides striking illustrations of thermodynamically-stable architectures, including tobacco mosaic virus, DNA, and numerous multimeric proteins. But in many other instances biological self-assembly is regulated in a number of characteristic ways.

2) The author introduces seven classifications of self-assembly processes, including strict (equilibrium) self-assembly, irreversible self-assembly, assembly following precursor modification, assembly with post-modification, assisted assembly, directed assembly, and assembly with intermittent processing. Strict self-assembly is governed by equilibrium thermodynamics. The virtues of self-assembly include minimization of information through use of modular subunits, control of assembly and disassembly, built-in error-checking and recovery, and overall high efficiency.

3) In many but not all instances self-assembly is a cooperative process involving nucleation and growth phases. A fundamental theme of cooperative assembly processes is that one series of interactions establishes the initial structure (nucleation), thereby setting the stage for a subsequent and more extensive series of interactions (growth). Cooperative phenomena are well- known in biochemistry, but cooperative assembly is not as well- developed conceptually in synthetic chemistry.

4) A striking feature of self-assembly is that forming several bonds can be easier than forming only one bond. Self-assembly can involve non-covalent and covalent bond formation. Self-assembly lies at the heart of myriad examples in chemistry, ranging from metal chelation to model systems for self-replication. Multi- bridged cage molecules provide one domain for comparing modern methods of one-flask syntheses with biological self-assembly, and the syntheses of over 100 such cage molecules are reviewed by the author. The rich precedents of biological self-assembly may yield new paradigms for synthetic chemistry. Molecular electronics is not alone in its requirement for controlled 3-dimensional architectures, and a deeper understanding of self-assembly in all its manifestations is expected to benefit many fields of chemistry.

New J. Chemistry 1991 15:15


"With the introduction of supramolecular polymers, which are polymers based on monomeric units held together with directional and reversible secondary interactions, the playground for polymer scientists has broadened and is not restricted to macromolecular species, in which the repetition of monomeric units is mainly governed by covalent bonding. The importance of supramolecular interactions within polymer science is beyond discussion and dates back to the first synthesis of synthetic polymers; the materials properties of, e.g., nylons, are mainly the result of cooperative hydrogen bonding. More recently, many exciting examples of programmed structure formation of polymeric architectures based on the combination of a variety of secondary supramolecular interactions have been disclosed. When the covalent bonds that hold together the monomeric units in a macromolecule are replaced by highly directional noncovalent interactions, supramolecular polymers are obtained. In recent years, a large number of concepts have been disclosed that make use of these noncovalent interactions. Although most of the structures disclosed keep their polymeric properties in solution, it was only after the careful design of multiple-hydrogen-bonded supramolecular polymers that systems were obtained that show true polymer materials properties, both in solution and in the solid state. Polymers based on this concept hold promise as a unique class of novel materials because they combine many of the attractive features of conventional polymers with properties that result from the reversibility of the bonds between monomeric units. Architectural and dynamic parameters that determine polymer properties, such as degree of polymerization, lifetime of the chain, and its conformation, are a function of the strength of the noncovalent interaction, which can reversibly be adjusted. This results in materials that are able to respond to external stimuli in a way that is not possible for traditional macromolecules."

L. Brunsveld et al: Chem. Rev. 2001 101:4071

Related Background Brief:

SELF-COMPLEMENTARY QUADRUPLE HYDROGEN-BONDING MOTIFS AS A FUNCTIONAL PRINCIPLE: FROM DIMERIC SUPRAMOLECULES TO SUPRAMOLECULAR POLYMERS. The self-association of individual molecules can lead to the formation of highly complex and fascinating supramolecular aggregates. However, for binding motifs which rely only on hydrogen bonds, a combination of several such weak interactions is necessary to observe self- association in solution. Systems based on four hydrogen bonds in a linear array can be obtained which efficiently aggregate at least in chloroform. Besides the physical-organic characterization of these aggregates and the factors influencing their stability, such quadruple hydrogen-bonding motifs can also be used in the field of materials science to synthesize, for the first time, supramolecular polymers through the self-association of self-complementary monomers. As the formation of noncovalent interactions is reversible and their strength depends significantly on the chemical environment (for example, solvent, temperature), the macroscopic properties of such polymers can be controlled by variation of these parameters; hence a first step towards intelligent materials with tailor-made properties is made. C. Schmuck and W. Wienand: Angew Chem Int Ed Engl 2001 40:4363.


A.P. Alivisatos et al (University of California Berkeley, US) discuss supramolecular materials science, the authors making the following points:

1) The development, characterization, and exploitation of novel materials based on the assembly of molecular components is an exceptionally active and rapidly expanding field. For this reason, the topic of molecule-based materials (MBMs) was chosen as the subject of a workshop sponsored by the Chemical Sciences Division of the United States Department of Energy. The purpose of the workshop was to review and discuss the diverse research trajectories in the field from a chemical perspective, and to focus on the critical elements that are likely to be essential for rapid progress.

2) The MBMs discussed encompass a diverse set of compositions and structures, including clusters, supramolecular assemblies, and assemblies incorporating biomolecule-based components. A full range of potentially interesting materials properties, including electronic, magnetic, optical, structural, mechanical, and chemical characteristics were considered. Key themes of the workshop included synthesis of novel components, structural control, characterization of structure and properties, and the development of underlying principles and models.

3) MBMs, defined as "useful substances prepared from molecules or molecular ions that maintain aspects of the parent molecular framework" are of special significance because of the capacity for diversity in composition, structure, and properties, both chemical and physical. Key attributes are the ability in MBMs to access the additional dimension of multiple length scales and available structural complexity via organic chemistry synthetic methodologies and the innovative assembly of such diverse components. The interaction among the assembled components can thus lead to unique behavior.

4) A consequence of the complexity is the need for a multiplicity of both existing and new tools for materials synthesis, assembly, characterization, and theoretical analysis. For some technologically useful properties, e.g., ferro- or ferrimagnetism and superconductivity, the property is not a property of a molecule or ion; it is a cooperative solid-state (bulk) property -- a property of the entire solid. Hence, the desired properties are a consequence of the interactions between the molecules or ions, and understanding the solid-state structure as well as methods to predict, control, and modulate the structure are essential to understanding and manipulating such behaviors. As challenging as this is, molecules enable a substantially greater ability of control than atoms as building blocks for new materials and thus are well positioned to contribute significantly to new materials.

5) The diversity of components and processes leads to the recognition of the critical role of cross-disciplinary research, including not only that between traditionally different areas within chemistry, but also between chemistry and biochemistry, physics, and a number of engineering disciplines. Enhancing communication and active collaboration between these groups was seen as a critical goal for the research area.

Advanced Materials 1998 10:1297.


M-J. Kim et al (Kwang-Ju Institute of Science and Technology, KR) discuss supramolecular chirality, the authors making the following points:

1) Fundamental questions concerning chiroptical polymers arise from the characteristics of natural polymers, which have a one-handed helical conformation and show characteristic functionality in living systems.(1) Conformational chirality can be optically induced by the irradiation of photochromic molecules and polymers.(2-5) This phenomenon has been investigated for cases of many kinds of photochromophores, for example, azobenzenes,(2-4) overcrowded alkenes,(5) diarylethens, binaphthalenes, and spiropyranes.

2) Since the pioneering studies by Goodman (1967), the optical induction of supramolecular chirality has been widely studied using azobenzene-containing polymers. Azobenzenes are well-known chromophores for their photoinduced linear orientation via trans cis   trans photoisomerization. Photoinduced chirality changes in azopolymers have been reported for polymethacrylates,(2) polypeptides,(3) and polyisocyanates.(4) These azobenzene polymers contain chiral centers, and the chiral properties were investigated in solution using two different wavelengths as the light source.

3) The use of circularly polarized light has been demonstrated as a method for partially resolving a racemic mixture. Recently, Nikolova et al (1997) reported on the photoinduced chirality of amorphous and liquid crystalline azobenzene polymers by irradiation with circularly polarized light. The induced chirality of the azobenzene polymers was investigated as a function of the ellipticity of incident light. However, Iftime et al (2000) reported that circular dichroism is not induced in an amorphous azopolymer film by irradiation with circularly polarized light and proposed that liquid crystalline alignment represents one of the key factors in the creation of a chiral superstructure. Therefore, the issue of the origin of the photoinduced chirality of azobenzene polymer films irradiated by light with handedness is not clear.

4) The authors report an investigation of chirality photoinduction from amorphous and achiral azobenzene polymer films. The suggest their results demonstrate that liquid crystallinity is not a necessary condition for a material to exhibit photoinduced chiral properties.

References (abridged):

1. Circular Dichroism Principles and Applications, 2nd ed.; Berova, N., Nakanishi, K., Woody, R. W., Eds.; Wiley-VCH, Inc.: New York, 2000.

2. Angiolini, L.; Caretti, D.; Giorgini, L.; Salatelli, E. Macromol. Chem. Phys. 2000, 207, 533.

3. Pieroni, 0.; Fissi, A.; Ciardelli, F. React. Fund. Polym. 1995, 6, 185.

4. Muller, M.; Zentel, R. Macromolecules 1996, 29, 1609.

5. Feringa, B. L.; Jager, W. F.; Lange B. d. J. Am. Chem. Soc. 1991, 113, 5468.

J. Am. Chem. Soc. 2002 124:3504


S.P. Brown and H.W. Spiess (Max Planck Institute for Polymer Science Mainz, DE) discuss NMR methods for supramolecular systems, the authors making the following points:

1) In current polymer science, there is considerable interest in the design of well-ordered superstructures based on self-assembly of carefully chosen blocks. Of particular importance in this context are noncovalent interactions, e.g., hydrogen-bonding and aromatic pi-pi interactions. It has been demonstrated, for example, that linear polymers and reversible networks are formed from the self-assembly of monomers incorporating two and three 2- ureido-4-pyrimidone units, respectively, because of the propensity of these units to dimerize strongly in a self- complementary array of four cooperative hydrogen bonds. But such specific interactions are not a prerequisite for a well- controlled self-assembly: e.g., the self-assembly in bulk of dendritic building blocks into spherical, cylindrical, and other supramolecular architectures occurs as a consequence of both shape and complementarity and the demixing of aliphatic and aromatic segments.

2) Despite the presence of considerable order on different length scales, single crystals suitable for diffraction studies, and thus full crystal structures, are not available for such self- assembled supramolecular entities. If the mechanisms governing self-assembly are to be better understood, analytical methods capable of probing the structure and dynamics of these partially ordered systems are essential. In recent years, the field of solid-state nuclear magnetic resonance (NMR) has enjoyed rapid technological and methodological development, and advanced solid- state NMR methods are currently well placed to meet the challenge of modern polymer chemistry. In particular, with such methods much insight can be achieved with small amounts (10 to 20 milligrams) of as-synthesized samples.

Chem. Revs. 2001 101:4125


T.L. Nguyen et al (State University of New York Stony Brook, US) discuss supramolecular crystal engineering, the authors making the following points:

1) Crystal engineering (in this context, supramolecular synthesis) is an important problem that requires a detailed knowledge of intermolecular interactions. One would like to be able to choose appropriate molecules or sets of molecules and predict with confidence the manner in which they will crystallize. This is a difficult problem of great complexity, and indeed in many cases there may be no simple thermodynamic basis for a successful prediction. Crystallization is a kinetic process, and polymorphism often appears when it is most inconvenient. The authors suggest that chemists persevere with a certain confidence that by a clever design they will achieve the structural result they seek. Success is achieved either by wisely setting limited structural goals in the first place, or by making judicious use of ex post facto crystal design.

2) Despite these difficulties, one can still imagine a scenario where one could reliably predict the total structure of a crystal purely on the basis of knowledge of molecular properties. Total structure prediction would require specification of molecular geometry and orientation, unit cell dimensions, and the space group. The authors report that their simplified approach to this problem has been to identify molecular functionalities that will predictably and persistently lead to crystals containing defined network structures. Each chosen functionality has a size and shape that leads to characteristic repeat distances within its networks, and these molecular networks are substructures of the final crystal. The networks have repeat distances commensurate with the unit cell of the crystal, and their group symmetries are a subgroup of the space group of the final crystals. The distance parameters can be predicted, and a consideration of molecular symmetry combined with the symmetry of each anticipated intermolecular bond can lead one to the correct network symmetry. The authors state: "By combining good chemical insight with solid crystallographic principles, one can design or engineer crystalline solids that contain networks with desired structural features."

J. Am. Chem. Soc. 2001 123:11057


In general, in this context, "goniometry" involves the measurement of interfacial angles for the comparison of crystals of different development. William Wollaston (1766-1828) developed in 1809 a reflecting (optical) goniometer for use with small crystals: a fixed mirror is illuminated from a collimator so that part of the parallel beam falls on the crystal, which is fixed on an axis parallel to the mirror and a short distance above it, and is so adjusted that the edge of the facial angle to be measured is parallel to the axis. All the interfacial angles in a given zone can be found by rotation of the crystal.

Mark D. Hollingsworth (Kansas State University, US) discusses the history of crystal engineering, the author making the following points:

1) Legend has it that modern crystallography owes its roots to an accidental discovery reported in 1781 by the French physicist Rene Just Hauey (1743-1822) (1). While admiring a friend's mineral collection, Hauey dropped a particularly large crystal of Iceland spar (calcite), which cleaved into equivalent fragments. With keen insight, Hauey recognized that internal structure was related to external form, and after spending the next years smashing his mineral collection and those of his friends, he reckoned that all crystals were composed of a limited number of building blocks that were stacked together in simple ways. With the subsequent development of optical goniometry, polarized light microscopy, and other physical techniques, 19th-century chemists and crystallographers focused on macroscopic properties of crystals such as birefringence, optical activity, pyroelectricity (electric polarization caused by temperature change), and, later, piezoelectricity (electric polarization under external stress), which was discovered by Pierre and Jacques Curie in 1880. These efforts culminated in Paul Groth's Chemische Krystallographie (2), which documents in five volumes what was known about the external form and physical properties of more than 7000 organic and inorganic crystals that had been characterized by the beginning of the 20th century.

2) Groth's treatise and Hauey's deconstruction of macroscopic crystalline objects provide instructive contrasts with the modus operandi of modern-day solid state organic chemists and "crystal engineers", who have embraced the notion of the supramolecular "synthon" (3) as the critical design element for generating new materials. In its renaissance, as inaugurated by G.M.J. Schmidt and coworkers in the 1960s (4), solid state organic chemistry has focused on the molecular building blocks and their connections with the anticipation that reliable functional group interactions can be used to assemble a variety of useful molecular materials.

3) The synthesis of organic molecules relies on the strength of covalent bonds and on the relative rates of bond-forming processes to lead in a rational and step-wise process to the final product. It is therefore no surprise that many organic chemists have until recently shied away from crystal synthesis. For the supramolecular synthetic chemist, the specific goal is a macroscopic property, and the final product is often a moving target that changes each time the crystal synthesis yields something different from that predicted by the imperfect models we use. The fundamental difficulty for this field is that molecular crystals are held together by a multitude of weak interactions, and a huge number of free energy minima (polymorphs) exist within a few kilojoules/mol of the global minimum. The process of crystal engineering is therefore an iterative one that involves synthesis, crystallography, crystal structure analysis, and computational methods.(5)

References (abridged):

1. J. G. Burke, Origins of the Science of Crystals (Univ. of California Press, Berkeley, CA, 1966), pp. 83-85.

2. P. A. Groth, Chemische Krystallographie (Verlag von Wilhelm Engelmann, Leipzig, 1906-1919), vol. I-V.

3. G. R. Desiraju, Angew. Chem. Int. Ed. 34, 2311 (1995)

4. G. M. J. Schmidt, Pure Appl. Chem. 27, 647 (1971)

5. K. D. M. Harris, M. Tremayne, P. Lightfoot, P. G. Bruce, J. Am. Chem. Soc. 116, 3543 (1994)

Science 2002 295:2410


C.M. Drain et al (City University of New York, US) discuss porphyrin arrays, the authors making the following points:

1) With the increasing demand for the ability to sculpt matter into precise functioning devices of nanoscale dimensions, the molecular level design of functional materials is an overarching theme in much of the synthetic materials literature (1-5). Inspired by biological systems, the introduction of specific interactions is a route toward using the facile and energetically favorable production capabilities to self-assemble materials. Exploitation of nonspecific intermolecular interactions has resulted also in the formation of molecular electronic devices.

2) The authors report they have used self-assembly to form a square planar array of nine porphyrins mediated by coordination of exocyclic pyridyl groups on three different porphyrins to 12 trans-palladium dichlorides. In addition to modulating the size and distribution on surfaces, metalation of the porphyrin macrocycle enables one to design nanoscale systems with a host of photonic, magnetic, redox catalytic, and sensor capabilities. These functions have been well studied on metalloporphyrin monomers. Substitution of the peripheral R groups with long-chain hydrocarbons enables the design of nanoscale aggregates that, using nonspecific interactions, organize into two-dimensional arrays. The authors present an overview of the design capabilities for materials and devices by using porphyrin supramolecular arrays.

3) In summary: The authors report that tessellation of nine free- base porphyrins into a 3 ž 3 array is accomplished by the self- assembly of 21 molecular entities of four different kinds, one central, four corner, and four side porphyrins with 12 trans Pd(II) complexes, by specifically designed and targeted intermolecular interactions. Strikingly, the self-assembly of 30 components into a metalloporphyrin nonamer results from the addition of nine equivalents of a first-row transition metal to the above milieu. In this case each porphyrin in the nonameric array coordinates the same metal such as Mn(II), Ni(II), Co(II), or Zn(II). This feat is accomplished by taking advantage of the highly selective porphyrin complexation kinetics and thermodynamics for different metals. In a second, hierarchical self-assembly process, nonspecific intermolecular interactions can be exploited to form nanoscaled three-dimensional aggregates of the supramolecular porphyrin arrays. In solution, the size of the nanoscaled aggregate can be directed by fine-tuning the properties of the component macrocycles, by choice of metalloporphyrin, and the kinetics of the secondary self-assembly process. As precursors to device formation, nanoscale structures of the porphyrin arrays and aggregates of controlled size may be deposited on surfaces. Atomic force microscopy and scanning tunneling microscopy of these materials show that the choice of surface (gold, mica, glass, etc.) may be used to modulate the aggregate size and thus its photophysical properties. Once on the surface the materials are extremely robust.

References (abridged):

1. Alivisatos, A. P. , Barbara, P. F. , Castleman, A. W. , Chang, J. , Dixon, D. A. , Klein, M. L. , McLendon, G. L. , Miller, J. S. , Ratner, M. A. , Rossky, P. J. , Stupp, S. I. & Thompson, M. E. (1998) Adv. Mater. 10, 1297-1336.

2. Aviram, A. & Ratner, M. (1998) Ann. N.Y. Acad. Sci. 852, 1- 349.

3. Lehn, J.-M. (1990) Angew. Chem. Int. Ed. Engl. 29, 1304-1319.

4. Stang, P. J. & Olenyuk, B. (1997) Acc. Chem. Res. 30, 502-518.

5.  Lindsey, J. S. (1991) New J. Chem. 15, 153-180.

Proc. Nat. Acad. Sci. 2002 99:6498

Related Background Brief:

OPTIMIZATION AND CHEMICAL CONTROL OF PORPHYRIN-BASED MOLECULAR WIRES AND SWITCHES. Porphyrin molecular wires consist of porphyrin units fused to acene-type bridges and have been synthesized by the authors in a range of topologies including linear porphyrin octamers of length ca. 120 ?. The authors demonstrate, for some linear oligoporphyrins, how the electronic coupling between the end porphyrin units can be modulated by simple (possibly in situ) chemical modulation of the bridging units. Specifically, the chemical systems considered involve either pH-controlled protonation of bridge azines or conversion of bridge quinone or quinone dioxime rings to or from benzenoid or hydroquinone rings. In the most general terms, the electronic coupling through oligoporphyrin molecular wires is discussed in terms of a simple model in which complete end-to-end electronic delocalization is required in order to provide strong long-range interactions. Computationally, the authors monitored interorbital coupling using an appropriate mixture of density functional and ab initio SCF computational schemes. Finally, the authors examined bridge modulation of the intermetallic coupling in three homovalent bis-metallic oligoporphyrin systems. Results were obtained both using an effective two-level model, appropriate for spectroscopic properties, and using a more general scheme, appropriate for molecular conduction. N.S. Hush et al: Ann New York Acad Sci 1998 852:1.

Related Background Brief:

SELF-ORGANIZATION OF SELF-ASSEMBLED PHOTONIC MATERIALS INTO FUNCTIONAL DEVICES: PHOTO-SWITCHED CONDUCTORS. Linear porphyrin arrays self-assembled by either hydrogen bonding or metal ion coordination self-organize into lipid bilayer membranes. The length of the transmembrane assemblies is determined both by the thermodynamics of the intermolecular interactions in the supramolecule and by the dimension and physical chemical properties of the bilayer. Thus, the size of the porphyrin assembly can self-adjust to the thickness of the bilayer. An aqueous electron acceptor is placed on one side of the membrane and an electron donor is placed on the opposite side. When illuminated with white light, substantial photocurrents are observed. Only the assembled structures give rise to the photocurrent, as no current is observed from any of the component molecules. The fabrication of this photogated molecular electronic conductor from simple molecular components exploits several levels of self-assembly and self-organization. Charles M. Drain: pnas 2002 99:5178.


In general, "amphiphiles" are molecules with parts (groups) having diverse affinities for different solvents. For example, polar groups have an affinity for water, while hydrocarbon groups have an affinity for oils. Most detergents are amphiphiles, molecules with a polar head and a long hydrocarbon tail. In this context, however, possible solvent interactions are only one aspect of amphiphilic character. The important consideration is that amphiphiles tend to self-organize: groups of amphiphilic molecules will form stable domains of polar interactions and nonpolar interactions. For example, amphiphiles may form "micelles", spherical or cylindrical arrangements with an interior forming one interaction domain while the surface forms another interaction domain. Larger aggregates may form vesicles with diameters in the micron range.

A simple linear polymer is a chain molecule composed of monomers with two reactive sites (bifunctional monomers), with monofunctional terminal units. If more than one bifunctional monomer is present, the chain is known as a "copolymer". A copolymer in which a number of units of the same monomer are located adjacent to one another (in "blocks" of monomers) is called a "block copolymer". A "diblock copolymer" is composed of two types of monomers (e.g., A and B), and may be depicted thus: AAAAAABBBBBAAAAAABBBBBAAAAAAA.

In general, a "homopolymer" is any polymer made up of only one kind of constitutional repeating unit, e.g., cellulose, which contains only glucose as the monomeric unit.

A "Langmuir-Blodgett film" (Langmuir-Blodgett multilayer) is a film of molecules on a solid surface, the film with multiple layers made by dipping a plate into a liquid so that it is covered by a monolayer and then repeating the process. The technique enables a multilayer to be built up one monolayer at a time, and such layers have many practical applications.

A. Mueller and D.F. O'Brien (University of Arizona, US) discuss hydrated amphiphiles, the authors making the following points:

1) Hydrated amphiphiles form various phases as a function of molecular structure, temperature, concentration, and pressure.(1- 4), and there appears to be a one-to-one correspondence between the structures observed for hydrated amphiphiles and that for block copolymer.(5) Amphiphiles are characterized by having a hydrophilic headgroup attached to at least one hydrophobic tail. The unfavorable interfacial enthalpic interaction between the hydrophobic tail(s) of the amphiphile with the polar water molecules induces the former to aggregate with the hydrophobic tail(s) of other amphiphiles.(4) The hydrophilic headgroup therefore separates the water from the tail(s), in much the same way that the A-B junction of a diblock AB copolymer separates the two homopolymer blocks A and B. Self-organized arrays of noncovalently associated amphiphiles may exist as self-supported lamellar/vesicular, various bicontinuous cubic, or hexagonal/cylindrical phases. Amphiphiles are also frequently studied as supported assemblies, e.g., monolayers at the air- water interface, Langmuir-Blodgett, or self-assembled monolayers. During the past two decades or so, the understanding of each of these supramolecular assemblies has advanced significantly. This progress is a consequence of fundamental and applied research in many laboratories.

2) The advent of methods to polymerize supramolecular assemblies, first in monolayers in the 1970s, followed by bilayer vesicles in the early 1980s, and more recently in nonlamellar phases, i.e., cubic and hexagonal phases, has led to the creation of new materials, the development of new methods, and a widening perspective on the potential applications of these novel polymeric materials. These uses include the controlled delivery of reagents and drugs, the preparation of biological membrane mimics, the separation and purification of biomolecules, the modification of surfaces, the stabilization of organic zeolites, and the preparation of nanometer colloids, among others.

3) The concept of an area-minimizing surface has been used extensively to describe the morphologies of amphiphile/water systems.(2) The free energy of the system is described by the topology of the surfaces. In such an analysis, a spontaneous curvature term arises purely as a result of the fact that the dimensions of the microdomain are only a few orders of magnitude greater than that of the constituent molecules. This means that the shape of the interface is influenced by the interactions on a molecular level. In order for a system to achieve equilibrium, the various terms in the free energy expression, chief of which is the mean curvature, must be minimized. This theory has been extended to describe the effects of surface charge and branched alkyl chains on the formation of nonlamellar assemblies. The distribution of a mixture of lipids in nonlamellar phases has also been investigated.

References (abridged):

1. Lindblom, G.; Rilfors, L. Biochim. Biophys. Acta 1989, 988, 221-256

2. Gruner, S. M. J. Phys. Chem. 1989, 93, 7562-7570

3. Seddon, J. M. Biochim. Biophys. Acta 1990, 1031, 1-69

4. Evans, D. F.; Wennerstrom, H. The Colloidal Domain: Where Physics, Chemistry, Biology, and Technology Meet; VCH Publishers: New York, 1994.

5. Benedicto, A. D.; O'Brien, D. F. Macromolecules 1997, 30, 3395-3402

Chem. Rev. 2002 102:727


S. Zeena and K.G. Thomas (Regional Research Laboratory, IN) discuss photoactive chemical systems. The design and study of molecular and supramolecular photoactive systems have been actively pursued in recent years due to their potential applications in optoelectronic devices (e.g., molecular switches, sensors, transducers, and information processing and storage devices). Of particular interest is the design of molecular systems which undergo conformational changes analogous to the folding of proteins. Synthetic molecular systems and polymers which can fold into well-defined conformation in solution ("foldamers") through non-covalent interactions have been reported. These include 1) solvophobically driven conformational folding of phenyacetylene-based oligomers into ordered helical structures, and 2) the donor-acceptor interaction or aromatic groups leading to pleated structures. Conformational changes and molecular motions in photoactive molecular and supramolecular systems can be modulated by chemical, photochemical, or electrochemical methods, and such changes, when translated into optical or electronic properties, can form the basis of switching devices. The authors report they have designed two nonconjugated bichromophores which can fold and unfold by varying the solvent polarity or by the application of external stimuli such as heat or light.

J. Am. Chem. Soc. 2001 123:7859


C.J. Kuehl et al (University of Utah, US) discuss metals in supramolecules. Over the past decade, the use of metal coordination as a means to drive and preserve the formation of discrete molecular ensembles has become an established methodology in supramolecular chemistry. However, the level of complexity to which metal-mediated self assembly can develop as a general synthetic strategy has yet to be realized. Nevertheless, the design and construction of new supramolecular entities refine our understanding of the fundamental principles of molecular self-organization. So far, highly symmetric ring systems (e.g., molecular triangles, squares, pentagons, hexagons, etc.) have generally been the most successfully characterized species, because of their inherent simplicity over three-dimensional constructs. Typically comprising aromatic bridging ligands connected via transition metals, these "metallocyclophanes" have shown promise as a new class of functional receptor molecules that can act as hosts in host-guest complexes. Considering that metal-containing macrocycles often possess magnetic, photophysical, and/or redox properties not accessible from purely organic systems, studies in basic host-guest chemistry have broad implications for technologies such molecular sensing, separations, and catalysis. However, precise size and highly specific electrostatic and dispersion forces are required for selectivity, and for the most part this remains an important challenge for research.

J. Am. Chem. Soc. 123:9634


Y. Yokoyama et al (National Institute for Materials Science, JP) discuss selective assembly of supramolecular aggregates on a surface. The realization of molecule-based miniature devices with advanced functions requires the development of new and efficient approaches for combining molecular building blocks into desired functional structures, ideally with these structures supported on suitable substrates. Supramolecular aggregation occurs spontaneously and can lead to controlled structures if selective and directional non-covalent interactions are exploited. But such selective supramolecular assembly has yielded almost exclusively crystals or dissolved structures. In contrast, the self-assembly of adsorbed molecules into larger structures has not yet been directed by controlling selective intermolecular interactions. The authors report the formation of surface-supported supramolecular structures whose size and aggregation pattern are rationally controlled by tuning the non-covalent interactions between individual adsorbed molecules. Using low-temperature scanning tunneling microscopy, the authors demonstrate that substituted porphyrin molecules adsorbed on a gold surface form monomers, trimers, tetramers, or extended wire-like structures. The authors report that each structure corresponds in a predictable fashion to the geometric and chemical nature of the porphyrin substituents that mediate the interactions between individual adsorbed molecules. The authors suggest their findings indicate that careful placement of functional groups that are able to participate in directed non-covalent interactions will allow the rational design and construction of a wide range of supramolecular architectures adsorbed to surfaces.

Nature 2001 413:619


Directed motion is one of the more dramatic characteristics of many living systems, and the movements of simple organisms, particularly of single-celled organisms, have fascinated biologists ever since the invention of the microscope. Under a microscope, a motile protozoan may appear as large as a rabbit, but there are no muscles or nerves in the single cell that constitutes such an organism, and the riddle is clear: How is chemical energy transduced to directed mechanical and kinetic energy in primitive biological systems? Until the era of the electron microscope and molecular biology, little progress was made in answering this question. That has changed: in recent decades molecular biology has provoked a renaissance in studies of cell movements. But if much has been learned and the questions refined, our fascination with motion in primitive organisms has grown rather than diminished. For it has become apparent that directed motions in primitive biological systems are examples of molecular-scale engineering that is often astonishing. Vorticella, discussed below, is a ciliated protozoan common in ponds, a single-celled organism that can be envisioned as follows: Imagine a bell-shaped body 50 microns at its widest part. The rim of the open end of the bell is covered with cilia that beat synchronously to sweep water and nutrients into the open end of the body. The closed dome end of the bell is attached to a long thin stalk that may be 500 or more microns in length, and the far base of the stalk is attached to a leaf or to pond debris. When the organism is feeding, the stalk is extended. When the organism is physically or chemically disturbed, the stalk contracts like a spiral-shaped spring, quickly drawing the bell- shaped body of the organism to the protection of the debris where it is attached. First described by Anton van Leeuwenhoek (1632-1723), Vorticella is a legendary organism in biology. Many children receive inexpensive microscopes as gifts when they are ten or eleven years old, and these children often use their new microscopes to examine everything available, including local pond water. At the first sight of Vorticella -- the lovely bell-shaped body with its synchronously beating cilia, the body at intervals suddenly pulled back by the contracting spring of the stalk, the stalk and body then slowly extending again with the cilia resuming their synchronized beating -- such children are often spellbound by the dynamic world of the small. If the fascination endures, and if they are fortunate in life, they often become biologists.

L. Mahadevan and P. Matsudaira (Massachusetts Institute of Technology, US) present a review of recent research on cell motility, the authors making the following points:

1) The retraction of the stalk of Vorticella (and of other ciliates of this type: peritrich ciliates) is caused not by the sliding action of a motor protein but by a spring that operates according to a simple mechanism: the entropic collapse of polymeric filaments. Although they are considered unusual engines for motility, springs and ratchets composed of filaments and tubules power many of the largest, fastest, and strongest cellular and molecular movements. Just as muscles magnify forces and movements by a geometrical hierarchy, these unusual mechanochemical engines use a similar principle: small changes in a protein subunit are amplified by the linear arrangement of proteins in filaments and bundles. The authors suggest that, considering the biochemical and physical characteristics of several known molecular springs and ratchets, they apparently represent ancient and biologically commonplace molecular engines.

2) In general, biological springs are active mechanochemical devices that store the energy of conformation of proteins in certain chemical bonds that act as latches. In the absence of an external force, the potential energy is released and converted into mechanical movement when the chemical bonds are broken.

3) The contractile avoidance reaction of Vorticella, first described by Leeuwenhoek in 1676, is a dramatic example of an active mechanochemical spring. The body of Vorticella is attached to a leaf or to debris by a long slender stalk. Within the stalk lies a rod-like helical cytoplasmic organelle, the "spasmoneme". In its extended state, the spasmoneme is 2 to 3 millimeters long, depending on the species of ciliate. When exposed to calcium ions, but to no external energy source, the spasmoneme contracts in a few milliseconds to 40 percent of its length at velocities approaching 8 centimeters per second. Based on the hydrodynamics, the force of contraction is of the order of a millidyne, whereas the power generated is a few milliergs per second. In terms of specific power per unit mass, the spasmoneme is among the most powerful biological engines.

4) The authors state: "The dynamics and energetics of biological springs and ratchets are dominated by factors that are inconsequential on the large length scales associated with our everyday world. In a [biological] cell, viscous forces, Brownian motion, short-range hydrophobic interactions, screened electrostatics, and steric effects influence the kinetics of filament and subunit diffusion and growth. In this soft, wet, and dynamic world, structural features are dominated by filamentous and membranous objects, a constant reminder that all events at this level are mediated by interfacial interactions."

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