ScienceWeek

CHEMISTRY: ON CHIRALITY

The following points are made by Rasmita Raval (Nature 2003 425:463):

1) Chirality is widespread in nature and is fundamental to life. It arises from straightforward geometry -- any object that lacks inverse symmetry can exist in two distinguishable mirror images, called enantiomers. For example, our hands are chiral: the right hand is an enantiomer of the left hand, and neither can be superimposed on the other by translation or rotation. At a molecular level, right-handed and left-handed compounds often have very different effects, so it is crucial for industry to produce pure enantiomeric forms.

2) Louis Pasteur (1822-1895) introduced the concept of molecular chirality in 1848, when he observed that crystals of the chemical sodium ammonium tartrate tetrahydrate can form left-handed and right-handed structures(2). Since then, chirality has been the cornerstone of several scientific advances, from the deduction that carbon atoms possess a tetrahedral arrangement of bonds(3,4), to the realization that terrestrial life-forms have evolved to make use of right-handed sugars and left-handed amino acids.

3) The inherent chirality of living systems dictates extraordinary specificity in the recognition of chiral molecules, so that a molecule and its mirror image, whether it is a pharmaceutical, an insecticide, a herbicide, a flavor or a fragrance, will almost always elicit different biological effects. This specificity presents a problem for the industrial synthesis of these compounds -- chemists must control the three-dimensional spatial arrangements adopted by their products so that only the required enantiomer is produced. Underpinning this multibillion-pound global industry are chiral catalysts(5) that promote "enantiospecific" reactions in which only one of the mirror images is formed. Most of these reactions are homogeneous -- the reactants and the catalyst exist in the same phase (generally in solution). Heterogeneous catalysis, where the catalyst is in a different phase (usually solid) from the reactants, is a fledgling technology but is often a more active and robust system that enables the products of the reaction to be separated from the catalysts much more easily. Central to this new process is the ability to incorporate chirality in catalytic solids and surfaces.

4) An important question is how are chiral surfaces formed on symmetric, achiral solids? Although prevalent in the living, organic world, chirality is rarely found in catalytically active inorganic materials and surfaces. But this property can be transmitted from organic molecules to inorganic systems in a number of ways. For example, if organic "right-handed" (R,R)-tartaric acid enantiomers are adsorbed onto the symmetric, achiral surface of solid copper, the tartaric acid molecules assemble into a chiral template on the copper surface. This exposes chiral channels within which the copper atoms are available to react with other molecules. The entire assembly can assume the mirror image by adsorbing the "left-handed" (S,S)-tartaric acid enantiomer instead(1).

References (abridged):

1. Switzer, J. A., Kothari, H. M., Poizot, P., Nakanishi, S. & Bohannan, E. W. Nature 425, 490-493 (2003)

2. Pasteur, L. Ann. Phys. 24, 442 (1848)

3. LeBel, J. A. Bull. Soc. Chim. Fr. 22, 337 (1874)

4. Van't Hoff, J. H. Arch. Neerl. Sci. Exactes Nat. 9, 445 (1874)


5. Sheldon, R. A. Chirotechnology (Dekker, New York, 1993)

Nature http://www.nature.com/nature

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ON CHIRAL CATALYSTS

The following points are made by T.P. Yoon and E.N. Jacobsen (Science 2003 299:1691):

1) Although the principles underlying asymmetric catalysis with enzymes and small molecules are fundamentally the same (1), some striking and rather surprising differences have been noted. William S. Knowles, a pioneer in small molecule asymmetric catalysis, made the following key observation in his Nobel address: "When we started this work we expected these man-made systems to have a highly specific match between substrate and ligand, just like enzymes. Generally, in our hands and in the hands of those that followed us, a good candidate has been useful for quite a range of applications" (2). Indeed, the best synthetic catalysts demonstrate useful levels of enantioselectivity for a wide range of substrates. This is very important to synthetic chemists, who must rely on the predictable behavior of reagents and catalysts when planning new syntheses.

2) With a few important exceptions (such as certain lipases), such generality of scope is not observed in enzymatic catalysis. It is even more surprising that certain classes of synthetic catalysts are enantioselective over a wide range of different reactions. Such catalysts may be called "privileged structures," in much the same manner that the term has been applied in pharmaceutical research to compound classes that are active against a number of different biological targets (3). Privileged chiral catalysts offer much more than one might have imagined, creating effective asymmetric environments for mechanistically unrelated reactions.

3) In summary: One of the most active current areas of chemical research is centered on how to synthesize handed (chiral) compounds in a selective manner, rather than as mixtures of mirror-image forms (enantiomers) with different three-dimensional structures (stereochemistries). Nature points the way in this endeavor: different enantiomers of a given biomolecule can exhibit dramatically different biological activities, and enzymes have therefore evolved to catalyze reactions with exquisite selectivity for the formation of one enantiomeric form over the other. Drawing inspiration from these natural catalysts, chemists have developed a variety of synthetic small-molecule catalysts that can achieve levels of selectivity approaching, and in some cases matching, those observed in enzymatic reactions.(4,5)

References (abridged):

1. E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Eds., Comprehensive Asymmetric Catalysis, Volumes I to III (Springer, New York, 1999)

2. W. S. Knowles, Angew. Chem. Int. Ed. 41, 1999 (2002)

3. B. E. Evans, et al., J. Med. Chem. 31, 2235 (1988)

4. T. Katsuki, Synlett 281 (2003)

5. E. N. Jacobsen, W. Zhang, A. R. Muci, J. R. Ecker, L. Deng, J. Am. Chem. Soc. 113, 7063 (1991)

Science http://www.sciencemag.org

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