Pasteur molecules with mirror images

Six years later Sir John Herschel 13> observed that the algebraic sign of the optical rotation of quartz crystals could be correlated with their shape, and the dextro- and levorotatory crystals look like mutual mirror images. This correlation was extended from crystals to molecules by Pasteur 14>, who postulated that the spatial arrangement of atoms in the molecules is responsible for their optical activity, and the dextro-and levorotatory molecules are in a mirror image relation. 

Many substances can rotate the plane of polarization of a ray of plane polarized light. These substances are said to be optically active. The first detailed analysis of this phenomenon was made by Biot, who found not only the rotation of the plane of polarization by various materials (rotatory polarization) but also the variation of the rotation with wavelength (rotatory dispersion). This work was followed up by Pasteur, Biot s student, who separated an optically inactive crystalline material (sodium ammonium tartrate) into two species which were of different crystalline form and were separately optically active. These two species rotated the plane of polarized light equally but in opposite directions and Pasteur recognized that the only difference between them was that the crystal form of one was the mirror image of the other. We know to-day, in molecular terms, that the one necessary and sufficient condition for a substance to exhibit optical activity is that its molecular structure be such that it cannot be superimposed on its image obtained by reflection in a mirror. When this condition is satisfied the molecule exists in two forms, showing equal but opposite optical properties and the two forms are called enantiomers. 

Since the enantiomeric resolution of tartaric acid in 1848 by Pasteur, a longstanding issue is whether mirror-image molecules are energetically identical with respect to the origin of biomolecular homochirality [100]. In 1860 Pasteur first conjectured that the homochirality may come from certain intrinsically handed force existing in the Universe [1]. In 1898, Kipping and Pope reported experimental results in relation to NaC103 with l- and d-... 

Beginning with Pasteur s work in 1860 [4] the fields of stereochemistry and biology were dominated for almost nine decades by the phenomenon now called chirality. Chiral molecules are those for which a three-dimensional model of the molecule is not superimposable on the mirror image of the model. Since the operation determining the existence of chirality is reflection in a plane mirror, this... 

A molecule that cannot be superimposed on its mirror image is said to be chiral. When a carbon atom is bonded to four different atoms or groups of atoms, it is called a chiral carbon. Two stereoisomers that are nonsuperimposable mirror images of one another are a pair of enantiomers. As mentioned in Section 17.3, the chemical and physical properties of enantiomers are identical, with the exception that they rotate plane-polarized light to the same degree but in opposite directions. This is exactly the phenomenon that Pasteur observed with the mirror-image crystals of tartaric acid salts. 

Observations of this type were extremely important to Pasteur in that they permitted him to deduce requirements for chirality. He connected the concept of nonsuperimposable mirror images with the existence of chirality. Since quartz loses its optical rotatory power when dissolved or melted, he inferred that it was a helical arrangement of molecules in this particular solid that conveyed the given properties [17]. He also understood that solids could possess certain elements of symmetry and still exhibit optical activity (i.e., chirality) and therefore coined the term dissymmetry to describe materials whose mirror images were not superimposable on each other. 

While it was previously believed that all enzymes were composed of protein, it appears that this view is currently undergoing some alteration, as we will see. But it can certainly be said that the vast majority of enzymes are proteins (there are over 2000 known), and each has its own specific three-dimensional structure that is the key to its functionality. In the late 1800s Emil Fischer expressed this as the lock and key model An enzyme has a particular shape so that reagent(s) for the reactions it will catalyze fit into it and are held there for reaction— as a key fits into a lock (see Fig. 16.2). John Cornforth, an Australian chemist, used this model to explain why natural molecules are formed in only one of two possible mirror images—z mystery since Pasteur s work with tartaric acid and tweezers. Cornforth saw that the enzyme acted as a three-dimensional template and only one shape would come... 

Pasteur was convinced that there must be some molecular difference between the two salts, and he made the problem the subject of his first major piece of research. He prepared several salts of tartaric acid and found that in all cases the crystals were asymmetric (Pasteur used the term dissymmetric), and displayed hemihedral faces. Pasteur was tempted to speculate that such asymmetric crystals were typical of optically active materials, and were the manifestation of asymmetry of the molecules. He then found that crystals of the optically inactive sodium ammonium paratartrate also displayed hemihedral faces, but on careful examination he saw that two types of crystal were present, one the mirror image of the other (Figure 10.13). He carefully sorted some of the crystals by hand. Those with right-handed hemihedry gave a solution which was dextrorotatory and identical with a solution of sodium ammonium tartrate. A solution of equal concentration of the crystals with left-handed hemihedry rotated polarised light to an equal extent in the opposite direction. A solution of equal concentrations of each crystalline form was optically inactive. Pasteur thereby demonstrated that paratartaric acid was... 

By his discovery, he recognized that a direct relationship exists between molecular geometry and optical activity. This led him to propose that molecules that rotate plane-polarized light in equal but opposite directions are related as an object and its mirror image. However, it remained for two other chemists, Van t Hoff and Le Bel, to explain 25 years later exactly how the atoms could be assembled into such molecular structures. In the interim, Pasteur turned his attention with great success to the biological problems mentioned earlier, but it was his pioneering work on the resolution of racemic acid that led the way for other chemists to explain the relationship of chirality or handedness in molecular... 

The tartrate salts were then allowed to crystallize, and Pasteur noticed that the crystals had two distinct shapes that were nonsuperimposable mirror images of each other. Using only a pair of tweezers, he then physically separated the crystals into two piles. He dissolved each pile in water and placed each solution in a polarimeter to discover that their specific rotations were equal in amount but opposite in sign. Pasteur correctly concluded that the molecules themselves must be nonsuperimposable mirror images of each other. He was the first to describe molecules as having this property and is therefore credited with discovering the relationship between enantiomers. 

The quest for chiral selectors can be arbitrarily separated in two paths the synthetic route and the natural route. The synthetic route studies the chiral molecule evaluating possible interactions (Table 1) and designs a selector that will interact differently with an enantiomeric form than with its mirror image. The natural route follows Pasteur and uses the fact that the living world is made of countless chiral selectors and produces pure enantiomers. Once a natural chiral selector has been selected, it is tested with its natural chiral target(s) and with many other enantiomers. The observation of the results allows estimating a posteriori possible chiral mechanisms. 

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