10 May 2005: Remembrance of links past

Do molecules have memories? In a small number of reactions, it has appeared as though the achiral transition state can remember the chirality of the reactant, and thereby influence the enantiomeric selectivity of the product formation. Using ab initio calculations, researchers in Switzerland and Italy have now found a rational explanation for such spooky molecular memories. 

Bernd Giese and colleagues at the University of Basel, together with Massimo Olivucci’s team at the University of Siena reconsidered the only known example of a photochemical reaction that displays the so-called chiral memory effect. This reaction, reported by Giese’s group in 1999, involves the cyclisation of an N-alkylated alanine derivative to form a proline derivative. In the transition state, the alpha-carbon of the amino acid carries only three ligands, and is therefore deemed to be achiral. Nevertheless, the resulting proline derivative reproduces the original chirality with 92 per cent enantiomeric excess.

Following the reaction path in the ab initio computer model, the researchers could indeed confirm that the biradical, achiral transition state is formed. However, they also observed a network of hydrogen bonds around the temporarily achiral carbon. These bonds slowed down any rotation about the crucial bonds sufficiently to make them slower than the onward reaction to the chiral proline product. As Giese explains it, ’the chirality of the carbon atom is transferred to a chirality of the whole molecule’ for the duration of the short time interval when the carbon is one ligand short of its tetrahedral conformation. 

While the primary interest in this issue is of fundamental and theoretical nature, enantiomerically pure amino acids such as proline are important in pharmaceutical syntheses, such that the understanding of this unusual and ultimately beneficial conservation of chirality might become economically important one day.