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Chirosciences

Any three-dimensional object that is not superimposable with its mirror image is chiral, a term derived from the Greek ceri (chéri) signifying “hand”. Just as the right hand is the mirror image of the left hand, they are clearly not identical, although both have a thumb and four different fingers. Chiral molecules also have different properties when sampled by interactions with other chiral molecules, fields or forces.

 

drawingcenter.org, Nora May Klumpp

 

Flag of the Isle of Man and its mirror image

The Team Chirosciences within the Institut des Sciences Moléculaires de Marseille (iSm2) studies different aspects of the interactions or syntheses involving chiral molecules. Two molecules that are in in a mirror image relationship without being superimposable are stereoisomers which are called enantiomers. For instance the natural D-limonene which smells orange like is the (R)-(+) enantiomer while the (S)-(-) enantiomer smells more like freshly cut lemons with a piney, turpentine-like odor. The different taste and smell of many enantiomers is due to their supramolecular interactions with our receptors which being protein complexes are intrinsically chiral. The (R)-(+) enantiomer of limonene is also active as an insecticide and is a common additive in cleaning products to impart these with a fresh citrusy fragrance.

Molecular models of limonene (4-isopropenyl-1-methylcyclohexene) with geometries optimized with the HyperChem® Program Package (Gainesville, Florida). The equimolar mixture of enantiomers, the racemic DL limonene, is also called dipentene being a C10H16 hydrocarbon.

A tragic case in the history of pharmaceutical industry is related to the drug Contergan containing racemic thalidomide. While one enantiomer is a pain killer and soothing agent for morning illness, having being prescribed to many pregnant women, especially in Germany, the other enantiomer is a teratogen causing severe malformations to fetuses such as missing or shortened limbs, blindness and deafness. In the past half century from this disaster, the pharmaceutical industry has been imposed strict regulations where racemic compounds have to be resolved and the biological activity of each enantiomer or stereoisomer needs to be accurately evaluated. For example if less than 0.1 % of a wrong enantiomer, with a malevolent activity, remains present in an active pharmaceutical ingredient, the respective pharmaceutical company will not pass the strict regulations allowing to bring to market their chiral drug. Astonishingly, enantiopure thalidomide has beneficial effects for instance in the treatment of leprosy and skin cancers, and has been recently approved for their treatment


HyperChem® Program Package (Gainesville, Florida) optimized structures of the two enantiomers of thalidomide. Two slightly different conformers are shown due to the free rotation around the phthalamide N-C(sp3) single bond.

Light is also chiral and if it is plane polarized, enantiomers will rotate this plane in opposite directions. The clockwise or (+) rotation is called dextrorotatory while the (-) is termed laevorotatory from the Latin right or left, respectively. The specific rotation of a chiral compound is one of its molecular signatures and can be accurately measured with a polarimeter at certain wavelengths. Additionally, circularly polarized light can be absorbed differently by two enantiomers and this effect is the basis for circular dichroism (CD) spectroscopies which can probe either electronic transitions (ECD) or vibrational transitions (VCD) in the infrared spectral region.

In Marseille we are able to separate efficiently enantiomers by chiral chromatography. A chiral stationary phase will interact differently with enantiomorphic substrates which will be eluted at different times with a solvent allowing an efficient separation on a chromatographic column of both enantiomers. Supercritical CO2 can also be employed as a nonpolar solvent.

Several research directions are pursued by the 22 permanent staff members and some two dozens PhD and post-doctoral students of the Team Chirosciences which are summarized here.The list of permanent staff and their associated PhD and post-doctoral students, with E-mail addresses and telephone numbers is available on the left links.