Understanding Stereochemistry: Isomers, Chirality, and Enantiomers

1. Biological Chemistry First Year Organic Chemistry Lecture Nine : Stereochemistry Convener : Dr. Fawaz Aldabbagh

2. Isomers are different compounds that have the same molecular formula Constitutional isomers are isomers that differ because their atoms are connected in a different order Stereoisomers differ only in the arrangement of their atoms in space Geometric Isomers

3. Enantiomers are stereoisomers whose molecules are nonsuperimposable mirror images of one another Objects that are superimposable on their mirror images are said to be achiral Involves a tetrahedral sp3 atom Interchanging any two groups at a chiral centre (stereocentre) that bears four different groups converts one enantiomer into another

4. One structure can be superimposed on another If any of the attached groups onto the tetrahedral atom are the same, the centre is achiral. The ultimate way to test for molecular chirality is to construct models of the molecule and its mirror image and then determine whether they are superimposable Screwdriver is achiral Socks are achiral Golf club is chiral Gloves are chiral

5. Properties of Enantiomers Enantiomers have identical melting points and boiling points Enantiomers have identical solubilities in solvents Enantiomers have identical spectra and refractive index Enantiomers interact, and react with achiral molecules in the same manner Enantiomers interact and react with other chiral molecules at different rates Enantiomers rotate plane-polarised light by equal amounts but in opposite directions Chiral molecules are optically active Polarimeter is a devise used to measure the effect of plane-polarised light on an optically active compound

6. Nomenclature of Enantiomers (R-S) System Enantiomers have opposite configuration at the chiral or stereocentre Priority 1. Highest atomic number first; 2. If the first atom attached to the chiral centre has the same mass, then next set of atoms in the unassigned groups are examined; 3. We now rotate the formula (or model) so that the group with lowest priority is away from us; 4. Unsaturated substituents have greater priority than saturated substituents The Absolute Configuration

8. No Correlation between the direction of rotation of plane polarised light and the absolute configuration of a molecule Clockwise Rotation (+) – dextrorotatory Anti-Clockwise Rotation (-) – levorotatory An equimolar mixture of two enantiomers is called a Racemic Mixture It is Optically Inactive

10. Biochemical effects arise when molecules interact with biomolecules such as enzymes or receptors. These are constructed of chiral building blocks called amino acids. Therefore, the biomolecule only accepts molecules of a certain configuration or shape. Thus, only one enantiomer will fit into the receptor or enzyme active site S – induces a teratogenic response R – induces a hypnotic or seductive response Draw the R- and S- forms of thaildomide

11. Nobel Prize 2001 Professor William Knowles Professor Ryoji Noyori Professor K. Barry Sharpless For synthesis of optically active compounds – asymmetric synthesis SN2