Molecular Chirality in Chemistry and Biology: Historical Milestones

Abstract

Beginning early in the 19th century, developments in crystallography, optics, and chemistry in France set the stage for the discovery of molecular chirality by Louis Pasteur in 1848. He found that the crystallization of the sodium ammonium salt of paratartaric acid, a mysterious isomer of natural (þ)-tartaric acid (TA), produced two different crystal types that were non-superimposable mirror-image forms of each other. He separated the two types and found their optical rotations in solution opposite in direction and equal in absolute magnitude. This led him to conclude that paratartaric acid is a combination of two mirror-image molecule types of TA that are dissymmetric, an existing term he adapted to the connotation of todays chiral. In 1857, he found that the two enantiomers of TA were metabolized by a microorganism at drastically different rates, and thereby discovered biological enantioselectivity. In 1886, Italian chemist Arnaldo Piutti discovered d-asparagine and found that it tasted intensely sweet, in contrast to the known l-asparagine which had no taste. This was the discovery of stereoselectivity at biological receptors. As a result of advances in stereoselective synthesis and enantioselective chromatography during the last decades of the 20th century, in the 1990s the importance of molecular chirality in drug action and disposition began to receive serious attention from drugregulatory authorities and the pharmaceutical industry, the overall result of which has been the nearcomplete disappearance of racemic drugs as newly introduced pharmaceuticals.

Chiroptical Symmetry Analysis: Exciton Chirality-Based Formulae to Understand the Chiroptical Responses of Cn and Dn Symmetric Systems

“…While enantiomeric molecules present the same interaction with other achiral molecules, they may interact differently with other chiral molecules or entities. Besides its impact in the biological world being ubiquitous [1,2], chirality can also be exploited in other areas such as materials science. For example, the interaction of chiral compounds with light has been used for the construction of light-powered molecular motors [3] or in the development of more sensitive and specific sensors [4,5].…”

Chiroptical Symmetry Analysis (CSA): Exciton Chirality-Based Formulae to Understand the Chiroptical Responses of <em>C</em>_n and <em>D</em>_n Symmetric Systems

“…The application of the perturbation theory to the (originally degenerate) first electronically excited level yields an energy splitting, E, between these two states (usually named  and ) given by equation (2).…”

“…While enantiomeric molecules present the same interaction with other achiral molecules, they may interact differently with other chiral molecules or entities. Besides its impact in the biological world is ubiquitous [1][2], chirality can also be exploited in other areas such as materials science. For example, the interaction of chiral compounds with light has been used for the construction of light powered molecular motors [3] or in the development of more sensitive and specific sensors [4][5].…”

When Stereochemistry Raised Its Ugly Head in Coordination Chemistry—An Appreciation of Howard Flack

“…Not only was this description being used by the United Kingdom chemical community in the 1890s [20,21], but also had a long tradition in the German literature [22][23][24] being introduced by Naumann in 1856 [25] and treated at length in Schoenflies' 1891 text on crystallography [26]. The IUPAC has subsequently made recommendations on the basic terminology of stereochemistry [27] and Gal has published extensively on the early etymology of stereochemical terms [28][29][30][31][32].…”