The Story Behind the Link between Molecular Chirality and Crystal Shape

Here we describe the story behind the link between molecular chirality and macroscopic phenomena, the latter being a probe for the direct assignment of absolute configuration of chiral molecules. First, a brief tour of the history of molecular stereochemistry, starting with the classic experiment reported by Pasteur in 1848 on the separation of enantiomorphous crystals of a salt of tartaric acid, and his conclusion that the molecules of life are chiral of single-handedness. With time, this study raised, inter alia, two fundamental questions: the absolute configuration of chiral molecules and how a molecule of given configuration shapes the enantiomorphous morphology of its crystal. As for the first question, following the beginning of crystal structure determination by X-ray diffraction in 1912, it took almost 40 years before Bijvoet assigned molecular chirality through the esoteric method involving anomalous X-ray scattering. We have been able to address and link both questions through 'everyday concepts of left and right' (in the words of Jack Dunitz) by the use of 'tailor-made' auxiliaries. By such means, it proved possible to reveal, through morphology, etch patterns, epitaxy and symmetry reduction of both chiral and, paradoxically, centrosymmetric crystals, the basic chiral symmetry of the molecules of life, the alpha-amino acids and sugars.