Racemization as a stereochemical measure of dynamics and robustness in shape-shifting organic molecules

Abstract

Bullvalene is a structurally unique dynamic molecule thought to interconvert among 1.2 million degenerate isomers. The incorporation of different chemical substituents onto the bullvalene core should lead to a "shape-shifting" molecule that can interconvert among thousands of discrete structural isomers. Previous NMR spectroscopy and HPLC studies on substituted bullvalenes ascertained the fact that these compounds are dynamic, but they could not attest to whether the molecules are only interconverting among only a few isomers or if a multitude of structures are being accessed. Here we confirm the remarkable shape-shifting property of a tetrasubstituted bullvalene by means of a racemization experiment. We show that a single, though fleeting, chiral, enantioenriched tetrasubstituted bullvalene isomer can spontaneously equilibrate to a racemic population of dynamic compounds. Despite the fact that conversion from one enantiomer of a bullvalene isomer to the other may require dozens or even hundreds of rearrangements and involve many potential pathways, CD spectroscopy and HPLC analysis of different bullvalene populations showed that multiple pathways exist and result in the complete racemization of an initial enantioenriched chiral bullvalene. These oligosubstituted bullvalenes represent a very rare example of an entity that can spontaneously transform itself into different discrete structures using ambient thermal energy. The confirmation that these shape-shifting organic molecules are chemically robust yet structurally dynamic is an important step toward their further use as materials, sensors, and biologically active compounds.