Prepared by KH. Sadique Faisal ASST.LECTURER DEPARTMENT OF PHARMACY, NUB

 Isomers are classified into two main classes- ◦ Constitutional isomers  Chain isomers  Positional isomers  Functional group isomers  Metamerism &  Tautomerism ◦ Conformational isomers / Stereoisomers  Geometrical isomers or cis-trans isomers &  Optical isomers

 Connectivity of the atoms remain same unlike the constitutional isomers  But the orientation of atoms in space or spatial arrangement are different.  Stereoisomers have their atoms connected in the same sequence (the same constitution), but they differ in the arrangement of their atoms in space.  The consideration of such spatial aspects of molecular structure is called stereochemistry.

 Changing configuration means bonds are broken  A different configuration is different molecule  Changing conformation of a molecule means rotating about bonds, but not breaking them  Conformation of a molecule are readily interconvertible, are all the same molecule

 Enantiomers are non supersimposable mirror images of each other  Whereas diasteriomers are not mirror images of each other

 Contains chiral molecule  Isomers are non superimposable mirror images of each other  Chiral molecule is not identical with its mirror images  Relationship is enatiomeric  Cis trans isomers or conformational isomers  Not mirror images of each other  Because of restricted rotation of groups joined by a double bond Diastereomer

 Chirality Or it is called handedness. (from Greek Cheir- Hand)  We can tell if an object has chirality by examining the object and its mirror image.  Every object has a mirror image. Many objects are achiral. By this we mean that the object and its mirror image are identical, that is, the object and its mirror image are superposable one on the other.  A chiral object is one that cannot be superposed on its mirror image.

 A tetrahedral atom with  four different groups  is an asymmetric carbon ◦ A stereocenter is defined as an atom bearing groups of such nature that an interchange of any two groups will produce a stereoisomer. ◦ The interconversion does not occur spontaneously as it requires breaking covalent bonds

 Which atoms in each of the following molecules are chirality centers?

1. Chirality is a phenomenon that pervades the university. 1.The human body is structurally chiral. 2.Helical seashells are chiral, and most spiral like a right-handed screw. 3.Many plants show chirality in the way they wind around supporting structures. 2. Most of the molecules that make up plants and animals are chiral, and usually only one form of the chiral molecule occurs in a given species. 1.All but one of the 20 amino acids that make up naturally occurring proteins are chiral, and all of them are classified as being left handed (S configuration). 2.The molecules of natural sugars are almost all classified as being right handed (R configuration), including the sugar that occurs in DNA.

3.DNA has a helical structure, and all naturally occurring DNA turns to the right. 3. Chirality and biological activity: 1.Limonene: S-limonene is responsible for the odor of lemon, and the R-limonene for the odor of orange. THE BIOLOGICAL IMPORTANCE OF CHIRALITY

2.Carvone: S-carvone is responsible for the odor of spearmint, and the R-carvone for the odor of caraway seed. 3. Thalidomide: used to alleviate the symptoms of morning sickness in pregnant women before The S-enantiomer causes birth defect. 2.Under physiological conditions, the two enantiomers are interconverted. 3.Thalidomide is approved under highly strict regulations for treatment of a serious complication associated with leprosy THE BIOLOGICAL IMPORTANCE OF CHIRALITY

 Thalidomide’s potential for use against other conditions including AIDS, brain cancer, rheumatoid arthritis is under investigation.

 The origin of biological properties relating to chirality: ◦ The fact that the enantiomers of a compound do not smell the same suggests that the receptor sites in the nose for these compounds are chiral, and only the correct enantiomer will fit its particular site (just as a hand requires a glove of the ocrrect chirality for a proper fit). ◦ The binding specificity for a chiral molecule (like a hand) at a chiral receptor site is only favorable in one way.  If either the molecule or the biological receptor site had the wrong handedness, the natural physiological response (e.g. neural impulse, reaction catalyst) will not occur. ◦ Because of the tetrahedral stereocenter of the amino acid, three-point binding can occur with proper alignment for only one of the two enantiomers.

◦ Superposibility of the models of a molecule and its mirage:  If the models are superposable, the molecule that they represent is achiral.  If the models are nonsuperposable, the molecules that they represent are chiral. ◦ The presence of a single tetrahedral stereocenter ⇒ chiral molecule. ◦ The presence of a plane of symmetry ⇒ achiral molecule  A plane of symmetry (also called a mirror plane) is an imaginary plane that bisects a molecule in such a way that the two halves of the molecule are mirror images of each other.  The plane may pass through atoms, between atoms, or both.

 The achiral hydroxyacetic acid molecule versus the chiral lactic acid molecule: ◦ Hydroxyacetic acid has a plane of symmetry that makes one side of the molecule a mirror image of the other side. ◦ Lactic acid, however, has no such symmetry plane.

 DESIGNATION OF STEREOCENTER ◦ R. S. Cahn (England), C. K. Ingold (England), and V. Prelog (Switzerland) devised the (R–S) system (Sequence rule) for designating the configuration of chiral carbon atoms. ◦ (R) and (S) are from the Latin words rectus and sinister:  R configuration: clockwise (rectus, “right”)  S configuration: counterclockwise (sinister, “left”) ◦ Configuration: the absolute stereochemistry of a stereocenter.

1. Each of the four groups attached to the stereocenter is assigned a priority. 1.Priority is first assigned on the basis of the atomic number of the atom that is directly attached to the stereocenter. 2.The group with the lowest atomic number is given the lowest priority, 4; the group with next higher atomic number is given the next higher priority, 3; and so on. 3.In the case of isotopes, the isotope of greatest atomic mass has highest priority. 2. Assign a priority at the first point of difference. 1.When a priority cannot be assigned on the basis of the atomic number of the atoms that are diredtly attached to the stereocenter, then the next set of atoms in the unassigned groups are examined.

3. View the molecule with the group of lowest priority pointing away from us. 1.If the direction from highest priority (4) to the next highest (3) to the next (2) is clockwise, the enantiomer is designated R. 2.If the direction is counterclockwise, the enantiomer is designated S.

4. The sign of optical rotation is not related to the R,S designation. 5. Absolute configuration: 1.Groups containing double or triple bonds are assigned priority as if both atoms were duplicated or triplicated.