Picking the right key with microwave spectroscopy.

When Emil Fischer introduced the concept of "lock and key" to describe the interaction of an enzyme with a substrate, he had coined a phrase that has since been used as a metaphor by researchers in enzymology, supra-molecular chemistry, and self-assembly.

Molecular recognition--and especially chiral recognition--is a central concept in molecular biology and many fields of organic chemistry, and is frequently thought to be dominated by steric hindrance (perhaps taking Fischer's metaphor a little too literally). Nicole Borho and Yunjie Xu, MCIC, from the University of Alberta (U of A) quantified chiral interactions using high resolution microwave spectroscopy combined with ab initio calculations. Their model system consisted of propylene oxide and ethanol. Propylene oxide is chiral and rigid and can be understood as the "lock" in Fischer's analogy. Although ethanol, the "key," is achiral, it has two chiral conformers (gauche) corresponding to the orientation of the methyl group with respect to the O-H bond, and one achiral (trans) conformer (see Figure 2). Thus ethanol can orient itself in 6 different ways with respect to each of the 2 enantiomers of propylene oxide, for a total of 12 structures, forming 6 pairs of enantiomers. In their March 2007 cover article in Angewandte Chemie International Edition 46 (2007), 2276, the U of A researchers show that using enantiomerically pure (R) propylene oxide, each of the 6 conformers is "frozen out" in their molecular beam and can be observed by their distinct rotational spectrum (see Figure 3). The line intensity observed for each conformer points to their relative stability providing an energetic ordering. From this ordering, Borho and Xu concluded that the secondary hydrogen bond between the propylene oxide methyl group and the ethanol oxygen atom is the dominant influence on the stability of the complex. These weak interactions are very difficult to model and it would appear as if a very high level of theory is needed to describe molecular recognition to that level.

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