Τόμος 7 (1989) – Τεύχος 1 – Άρθρο 3- Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 7 (1989) – Issue 1 – Article 3 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

C. T. PLESSAS, S. T. PLESSAS AND A. BENAKIS

7: 15-32 (1989)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

7: 15-32 (1989)

Symmetry and the lack of it (or asymmetry) is a common phenomenon that can be seen in the letters of the alphabet (fig. 1) as well as in human body. All living organisms are constituted by ordered asymmetric biomolecules. The asymmetry is not only restricted to the biogenic compounds; a great number of xeno­biotics, including drugs, thought to be mono-substances are in fact mixtures of stereoisomers, i.e. molecules with the same molecular formula, but different in respect to the spatial arrange­ment of certain atoms or groups. This arrange­ment is called configuration and its is based on the concept of tetrahedral carbon (fig. 2). Compounds of the formula Cabcd exist in two forms that are not superimposable; they are mirror images of one another (fig. 3) and they are called optical isomers, optical antipodes, enan­tiomorphs or enantiomers. Optical isomers rotate the plane of polarised light to the right (dextrorotatory or dextrogire molecule) or to the left (levorotatory or levogire molecule) (fig. 4). This optical activity depends on substance concentration, temperature, light wavelength, solvent and pH of aqueous solutions. The necessary and sufficient condition for a sub­stance to show optical activity is that the molecule is asymmetric (or dissymetric or chiral). These molecules possess a chiral center (C-chiral, N-chiral, P-chiral), a chiral plane or a chiral axis (fig. 5). A mixture of equal parts of enantiomers is a racemic modification or racemate and is optically inactive. Α pure enantiomer can be racemised by usually drastic means (fig. 6). Α molecule with two or more chiral centers can exist as four stereoisomers, that they are two different racemates; those stereoisomers that are not enantiomers are called diastereoisomers or diastereomers (fig. 7 and 8) and they are not related as object and its mirror image. Geometric isomers, or cis-trans­ configurations, are a particular kind of diaste­reoisomers that owe their existence to hindered rotation about double bonds (fig. 9). Stereoiso­mers may be described by: (a) the direction of polarised light plane rotation; this is indicated by the signs (+) and (-) or by the letters d and I; (b) the Fischer Convention, i.e. the configuration about a chiral atom in relation to a reference molecule, the D(+)-glyceraldehyde (fig. 10); the molecule under investigation must be chemically conver­ted to glyceraldehyde or to another molecule of known configuration; (c) (best) the sequence rule: R (rectus) / S (sinister) system or Cahn-Ingold-Prelog Convention (fig. 11); this system describes the actual configuration. The same system is also the base of the assignment of geometric isomers as Ζ or E configurations (fig. 12). Conformations are different arrangement of molecules that can be converted into one another by rotation of single bonds. In ethane coexist staggered and eclipsed conformations with a infinite number of skew conformations (fig. 13). There are several different staggered conformations: one anti and two gauche (fig. 14). Cyclohexane exists in various different confor­mations: chair, half-chair, boat and twist-boat (fig. 15); the chair form is the most stable conformation of cyclohexane, and of nearly every derivative of cyclohexane, while boat form is not actually a conformer, but a transition state between chair and twist conformations. Chair conformations of cyclohexane exist in an equatorial and in an axial position (fig. 16), the former being more stable than the latter (fig. 17).

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