Chiral catalysis-driven rotary molecular motors

The structural anisotropy necessary to distinguish clockwise from counter-clockwise motions in motor-molecules that continuously rotate about a covalent single bond has previously been supplied through the use of chiral chemical fuels or with enzymes. Here we report on a new class of chiral azaindole–phenylethanoic acid rotary motors in which, like motor proteins, anisotropy is inherent through structural asymmetry in the motor itself. The motor-molecules consist of a 7-azaindole group attached through a C–N bond to a phenyl ring bearing a 2-(R or S)-(alkyl)ethanoic acid side chain. As the carboxylic acid group of the motor catalyses hydration of a carbodiimide fuel, the phenyl ring continuously directionally rotates about the azaindole stator. The stereogenic centre on the rotor side chain gives rise to diastereomeric conformations in both of the chemically distinct states (carboxylic acid and acyl-pyridinium) of the motor during the catalytic cycle. This generates a directional bias of 8:1 (clockwise:counter-clockwise; alkyl substituent = C6H5CH2-) for motor rotation powered by an achiral fuel, diisopropylcarbodiimide. The addition of one enantiomer of a hydrolysis promoter to the fuelling system increases the directionality of clockwise motor rotation to >30:1 (alkyl substituent = CH3-). The addition of the other enantiomer reverses the direction of catalysis-driven motor rotation (1:2 clockwise:counter-clockwise; alkyl substituent = CH3-). The experimental demonstration that a chiral molecular rotary motor can be powered by the same chemical fuel to rotate either with, or counter to, the motor’s dominant power stroke informs the understanding of how chemical energy is transduced through catalysis, the fundamental process that powers biology.