Molecular dissymmetry

Within this historical setting, the actual birth of stereochemistry can be dated to independent publications by J. H. van t Hoff and J. A. Le Bel within a few months of each other in 1874. Both scientists suggested a three-dimensional orientation of atoms based on two central assumptions. They assumed that the four bonds attached to a carbon atom were oriented tetrahedrally and that there was a correlation between the spatial arrangement of the four bonds and the properties of molecules, van t Hoff and Le Bell proposed that the tetrahedral model for carbon was the cause of molecular dissymmetry and optical rotation. By arguing that optical activity in a substance was an indication of molecular chirality, they laid the foundation for the study of intramolecular and intermolecular chirality. 

This report presents various methods developed primarily at our laboratory for chromatographic resolution of racemates of several pharmaceuticals (e.g., -blockers, NSAIDS, anta-acids, DL-amino acids, Bupropion, Baclofen, Etodolac, Carnitine, Mexiletine). Recently, we developed methods for establishing molecular dissymmetry and determining absolute configuration of diastereomers (and thus the enantiomers) of (/< .S )-Baclofcn, (/d.SJ-Bctaxolol with complimentary application of TLC, HPLC, H NMR, LCMS this ensured the success of diastereomeric synthesis and the reliability of enantioseparation. 

When the 2-methyIisoarsindoline (28 R = Me) is quaternized with an o-xylylene dibromide, a spiroisoarsindolinum salt (35) is formed (45JCS30). The unsubstituted salt (35 R = H) is symmetrical about the heteroatom, but the 5-chloro substituted salt (35 R = Cl) should possess molecular dissymmetry and would be expected to exhibit optical activity. Attempts to resolve this material with optically active anions were not, however, successful (47JCS662). 

For further discussion of these methods, see Mason, S. F. Molecular Optical Activity and the Clurd Discriminations Cambridge University New York, 1982 Saito, Y. Inorganic Molecular Dissymmetry-, Springer-Veriag Berlin, 1979. 

Corey. E. J. Bailar. J. C., Jr. J. Am. Chem. Soc. 1959.81,2620-2629. The e Ur classic paper in the field i jon wtach all of the subsequent work has been based. See also Sajlo, Y. Inorganic Molecular Dissymmetry-, Springer-Vedag Beriki. (979 Chapter J. 

Bijvoei. J M. Endearor. 1955. 14, 71-77. See also Saito, Y. Inorganic Molecular Dissymmetry Spnnger-Verlag Berlin, 1979 Chapter 2. 

Y. Saito, Inorganic Molecular Dissymmetry , Springer-Verlag, New York, 1979. 

On the basis of his discoveries, Pasteur postulated that optical isomerism had to be related to the molecular dissymmetry of substances such that nonidentical mirror-image forms could exist. However, it remained for van t Hoff and Le Bel to provide, almost simultaneously, a satisfactory explanation at the molecular level. In his first published work on tetrahedral carbon van t Hoff said .. . it appears more and more that the present con-... 

Optical activity was first observed with organic compounds having one or more chiral carbon atoms (or centres) (i.e. a carbon substituted with four different groups). In the structures (1) to (17) the chiral carbons are specified with an asterisk. Subsequently compounds having chiral centres at suitably substituted heteroatoms (e.g. silicon, germanium, nitrogen, phosphorus, arsenic, sulphur, etc.) were also synthesised. Molecular dissymmetry, and hence chirality, also... 

Easson, L. H., Stedman, E., Studies on the relationship between chemical constitution and physiological action. V. Molecular dissymmetry and physiological activity. Biochem. J. 1933, 27, 1257-1266. 

Mukhopadhyay P, Wipf P, Beratan DN (2009) Optical signatures of molecular dissymmetry combining theory with experiments to address stereochemical puzzles. Acc Chem Res... 

We will show in this chapter that a designed combination of thermodynamic and/or kinetic control of the self-assembly processes has allowed us to develop various applications all based on the induced chirality in the porphyrin Soret band absorption region. Chiral information transfer has been followed using circular dichroism, a spectroscopic technique particularly useful to characterize (supra) molecular dissymmetry or chirality [3]. 

As noted earlier, Ogston was, in 1948, not aware of the 1933 paper by Easson and Stedman [25]. However, in that paper, those authors had taken an important conceptual step. From the three-point attachment postulated for the enantiomer of Cabcd with a receptor they supposed that the dissymmetry of 5 is abolished by replacing the group a by a second group b, the resultant molecule, represented by 16, retains unchanged that part of the structure of 5, i.e., the base bed of the tetrahedron, which is concerned with its attachment to the specific receptor and must therefore be considered capable, despite the absence of molecular dissymmetry, of... 

Mole then undertook research towards a Ph.D. with Eustice Turner at Bedford, which she was awarded in 1938. She continued research with Turner for another year, investigating molecular dissymmetry due to restricted rotation in diphenylamines and triphenylamines, before obtaining an appointment with ICI, first at Widnes, then in the Technical Services Department in Liverpool. One of her nominators in 1941 for admission as Fellow of the Chemical Society was ICI Librarian, Mary Eynon Miller (see above). 

The fundamental requirement for the existence of molecular dissymmetry is that the molecule cannot possess any improper axes of rofation, the minimal interpretation of which implies additional interaction with light whose electric vectors are circularly polarized. This property manifests itself in an apparent rotation of the plane of linearly polarized light (polarimetry and optical rotatory dispersion) [1-5], or in a preferential absorption of either left- or right-circularly polarized light (circular dichroism) that can be observed in spectroscopy associated with either transitions among electronic [3-7] or vibrational states [6-8]. Optical activity has also been studied in the excited state of chiral compounds [9,10]. An overview of the instrumentation associated with these various chiroptical techniques is available [11]. 

T.M. Lowry, Molecular dissymmetry. Chapter 2, Optical Rotatory Power, Longmans, Green, Co, London, 1935, pp. 25-36. 

Sailo, Y. Inorgiitiic Molecular Dissymmetry Spnnger-Verlag Berlin, 1979 p 136. Nole that Ihe iris(ala) complex has a different chromophore (CoNjO ) than the Iris(diaminc) complexes (CoN ). and so the resemblance is only approximate. 

For a full discussion of gcometnc isomerism, see Saito. Y. Inorganic Molecular Dissymmetry, Springer-Verlag Berlin, 1979 pp 6-7, 73-88. 

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