Molecular motor functions as switch in enantiomer-selective reactions

The Groningen chemists Prof. Ben Feringa and Dr Jiaobing Wang have discovered a way to use a molecular motor as a catalytic system for enantiomer-selective synthesis reactions. The system can produce various forms of chiral molecules at will. The research was published last week in the academic journal Science.

Many organic-chemical molecules exist in two mirrored variants, comparable to a right and a left hand. In chemical jargon, these variants are called enantiomers (opposite) or chiral (from the Greek word for hand).

During a normal chemical synthesis, both types of enantiomers are created in equal quantities, known as a racemic mix. By using catalysts, however, it is possible to make mixtures with one of the two forms in a much greater quantity, known as enantiomer-selective synthesization. Feringa’s department has conducted a great deal of research in this field.

Medicines

Enantiomer-selective synthesis reactions are economically very important, particularly in the production of medicines. Often only one mirrored form has medicinal properties, and the other is superfluous or can even result in undesired side effects. In the system that Feringa and Wang have just published, the configuration of the molecular motor determines which mirrored form is produced.

Molecular motor

Feringa invented the molecular motor in 1999. It is a molecule that comprises a fixed part (the stator) and a rotating part (the rotor), linked by an axis. The rotor has four reaction steps, three of which are important for the catalytic system.

Combination

The catalytic system in the new Science article links the two research lines in Feringa’s group – enantiomer-selective catalysis and the molecular motor.

The system links two catalysts which have long been known to have an enantiomer-selective effect to the ends of the stator and rotor. In the configuration where the catalysts are as far apart as possible (known as the trans-stand), a racemic mix is produced. In the next configuration, where they stand virtually above each other (a cis-stand), the preference is for one particular mirrored type, while in the next step in the sequence of the rotor (also a cis-stand) produces the other mirrored variant.

Model reaction

The Groningen chemists demonstrate this in the Science article with the help of a model reaction: a Michael Addition where 1-methoxy thiophenol is linked to cyclohexenone. The product reaction varies from 49/51 percent (trans, racemic) to 75/25 (M-cis) and 23/77 (P-cis) percent of the enantiomer forms.

The selectivity is created because during the reaction process, the two components are each captured separately by a catalytic end and thus end up at a certain angle opposite each other. This angle changes depending on the configuration of the motor.

The Groningen chemists expect the molecular motor – used here not so much as a motor but as a switch – may in the future become an important development instrument for performing multiple enantiomer-selective reactions one after the other, whereby the catalyst can be adapted as required.

Note for the press

More information: Prof. B.L. Feringa

For the article see: http://www.sciencemag.org/content/early/2011/02/09/science.1199844.abstract