General scope

The microsymposium "Large Supramolecular Assemblies and Inclusion Compounds" organized during ECM-18 was devoted both to specific crystalline compounds and to general questions pertaining to further developments in the supramolecular (SM) field.

The content and scope of the SM field has undergone large changes during the last 10 years. The original target aimed mainly at inclusion compounds involving recognition and association steps. This area comprises crystalline hydrates and other clathrates, as well as individual "supermolecules" already existing in solution such as cyclodextrins, calixarenes, or crown ethers.

Soon it appeared that a fruitful new research direction in Supramolecular Chemistry arises by studying and using non covalent forces (hydrogen bonds, Van der Waals forces, p -p interactions, coordination bonds) issued from each molecule at all directions. Thus pre-designed molecular recognition involving many molecules occurs and leads to a molecular assembly with specific architecture and properties.

A further step consists of "imprinting information" into molecular components (by creating chemical functions with pre-designed geometry) so that upon mixing of the components a supermolecular entity is spontaneously generated by molecular recognition. and self assembly. This enlarged field allowed in turn further developments in the inclusion area.

It is remarkable that novel large assemblies comprise synthetic entities with molecular weights as high as 15000, as well as hybrid SM assemblies of synthetic molecules with DNA.

Clearly the supramolecular discipline heavily relies on 3D structural information at "both ends": in the process of designing a new compound, and in the process of characterization of the final product. In this general description, crystallographers immediately recognize most of their motivations and their views on the very essence of a crystal, of a complex molecule, of a molecular assembly. Crystallization itself is a prototype of a self-assembly process, and some crystallographers have further focused on "the crystal as a supramolecule".

It is worth noticing that the role of crystallography is widely recognized, and it is now of general use that the displayed chemical formulas be computer outputs of crystal structure determination. In particular, crystal engineering, boosted by current achievements in the supramolecular area, is now rapidly developing.

Prediction of crystal structures has ever been a subject of tantalising work. A turning point is being reached by current structure investigations of crystals involving supramolecular features or assemblies originating from molecular and supramolecular recognition. The concept of building blocks and synthons endowed with directional linking functions undergoes vigorous new developments. Several novel crystalline SM families are based on the synergy between different types of non covalent bonds.

The supramolecular discipline provides fruitful interface to other disciplines, such as biology, materials sciences, supramolecular polymers (in particular dendrimers), and recently with supramolecular physics.

Thus, crystallography is a necessary, quasi-indispensable part in any supramolecular area:

- as fundamental source of information in the initial process of conception and design (retro-synthetic methods, synthons), often retrieved from data banks (CSD, PDB).

- for the creation and optimization of new classes of crystalline compounds and solid state synthesis with specific properties

Natural or semi-natural compounds

Higher cyclodextrins homologues, larger than cyclooctaamylose, show quite unusual conformations based upon a reversal of the usual mutual orientation of consecutive glycose rings. The isolation and crystallisation of cyclodextrins with 9,10,14,16 and 26 rings is a remarkable achievement. It provides a wealth of information on the difficult question of saccharide conformation whose variability causes problems in crystal structure determination of glycoproteins and other important biological structures. A new model for V-amylose proposed by the authors is a nice example of further implications of a crystallographic structure determination (K. Gessler et al).

An almost total chiral separation from a racemic mixture of a pheromone has been achieved based on the chiral cavity of a trimethylated cyclodextrin. It should be emphasized that here chiral discrimination and separation only involves van der Waals forces or very weak polar interactions, and this sheds new light on the importance of appropriate supramolecular crystalline compounds synthesized for a specific purpose (I. Mavridis et al).

The crystal structure of several salts of bile acids allowed to identify structure models to represent micellar aggregates in aqueous solutions. These aggregates play a crucial role in the biliary stone formation and dissolution (Candeloro et al).

Further studies on complexation by beta-cyclodextrin concern aroma glycosides, where the aroma (menthol) is included in the cavity, while the glycoside moiety is involved in intermolecular hydrogen bonds (Malpezzi et al).

Materials

Porphyrins, a chemical family originally known from biology, are interesting versatile materials where a suitable substitution is used to control the modes of supramolecular association of these metal binding molecules for various purposes (photosynthetic systems, nanoporous solids and others). Crystal structure design and determination combined with chemical synthesis provide here an important area of crystal engineering (I. Goldberg et al).

A new work has shown that a single urea inclusion crystal containing a given hydrocarbon derivative can undergo continuous replacement by another hydrocarbon entering from one end of the crystal and pushing out the original guest at the other end. This spectacular experiment leads to enantiomeric discrimination and illustrates the paramount importance of precise supramolecular interactions in a well defined system A.A. Kahn et al).

Ionophores and inclusion compounds

Crystals of protonated calixarenes exhibit specific supramolecular assemblies greatly depending on the metal chloride anions (A. T. Gubaidullin et al)

Larger anions such as azodibenzoate derivatives are selectively included in a specific cationic receptor both in solution and in the crystal state. This complexation is able to modify the cis-trans photoequilibrium of the guest (M. Cesario et al).

A phosphate calix-type host has a specific stereochemistry favorable to intra-cavity strong complexation of cationic species (B. Tinant et al).

Coordination supramolecular compounds

New bis-macrocyclic Ni receptors have been synthesized and their ability to bind small organic guests has been explored (A.Olszewska et al).

A crystalline species from a solution of Ni complexes with oxime ligands proved to have a very complicated nonameric metallacrown complex moiety (A. Pajunen et al).

Conformational studies of several novel oxime ligands are an important step for their further use in coordination complexes (I.O. Fritzky et al)

General structural information on supramolecular assemblies

Crystallographic studies of oxime carboxylic acid systems provide further data on supramolecular synthons (M. Kubicki et al).

Methodologies discussed during the closing panel session

Upgrading and combining methodologies is presently the main theme of active research. Producing large SM assemblies and obtaining structural information is so difficult, that a single technique is not sufficient. Various methods are used and combined such as Computer Simulations, Solid State NMR, Electrospray Mass Spectroscopy, Single-Molecule Force Spectrometry, Time Resolved Diffraction and others.

Crystallisation of SM compounds is still a major problem and a subject of active research, yet some spectacular achievements have been recorded. It is to be noted that crystal growth of biological macromolecules has reached a high level of performance and is the object of special meetings.

Thermodynamic and kinetics data are clearly important aspects for the formation and decomposition of SM compounds. The determination of the pertinent data is often long and requires instrumentation with high precision. A special equipment has been developed to measure the kinetics of enclathratetion and desolvation. The activation energies have been evaluated and correlated with other data (L. Nassoibeni et al).

The quick and precise data collection using synchrotron single crystal diffraction is now an important facility, especially appreciable for supramolecular crystals which are often difficult to grow. The Discussion Session with the participation of Dr Kvick (ESRF, Grenoble) dealt with difficult problems at the limit of the today instrumentation (W. Clegg).

Recent developments of Direct Methods have found a successful application in large SM compounds and assemblies (talk by I. Uson, group of G. Scheldrick). It is worth emphasising that the SM synthesis - by assembly or self-assembly of large number of molecular components - is likely to produce bigger and bigger supermolecules. Direct methods are clearly the most suitable, if not the only, method of crystal structure determination for 500 - 1000 atom assemblies.