Organic Chemistry (Sterio Chemistry)

ORGANIC CHEMISTRY (STEREOCHEMISTRY) Hybridization: Hybridization Bond Geometry Angle Sigma Pi bonds % of S % of P Example Bonds sp3 109 28′ Tetrahedral 4 None 25 75 CH4 sp2 120 Planer 3 1 33.33 66.66 CH2=CH2 sp 180 Linear 2 2 50 50 HC≡CH Graphical Representation:  Fisher Projection  Wedge Projection  Newman Projection  Haworth Projection  Sawhorse Projection Stereoisomers: Formula to calculate number of possible stereoisomers, X = 2n Where, X = possible stereoisomers N = no. of stereogenic centers/ chiral molecules Isomers (Same Mol. Formula & diff. Structural Formula) Constitutional Isomers   Stereoisomers Functional group Sequential isomers Conformational Isomers Configurational Isomers Low energy of interconversion, High energy of interconversion e.g. Cyclohexane to n-hexane Distereomers Enantiomers Not mirror images of each other Non-superimposable mirror images of each other Cis, trans isomers Diastereomers containing stereogenic centers Chirality: (Gr,: Cheir = hand) Word chirality refers to asymmetry (left and right hand), i.e., mirror images of each other. Stereoisomers:  (+) Carvone = S-configuration present in Caraway  (-) Carvone = R-configuration present in Spearmint  (+) Limonene = Orange & (-) Limonene in Lemon  (-)Epinephrine has more potent pressor activity than (+)Epinephrine due to OH group in the binding site.  Nature makes only (-)Brucine  Enzymes are chiral.  Natural amino acids are chiral, except Glycine.  Most of the L-amino acids present in our body have S-configuration. Invertomers: One enantiomer inverts rapidly into another. Such enantiomers are called Invertomers. Diastereomers: Stereomers that are not mirror images of each other are called Diastereomers.  (+)Tartaric acid and meso-tartaric acid are diastereomers of each other  (-)Tartaric acid and meso-tartaric acid are diastereomers of each other  (+)Tartaric acid and (-)Tartaric acid are enantiomers of each other  L-Erythrose is enantiomer of D-erythrose  L-Threose is diastereomer of D-erythrose Examples of Enantiomers and Diastereomers Acetylcholine (ACh): (+)trans is a much more active agonist of the muscarinic receptor of ACh than (-)trans-isomer. None of the cis-isomers have any activity. Thalidomide: Sold as racemic mixtures in Germany, as sedatives for pregnant women. S(-) is a strong teratogen, but the R(+) is safe and used as antimicrobial in treatment of leprosy. Aspartame: Sold as L,L-isomer, which is sweet and the L,D-isomer, which is bitter. Menthol: (-) Menthol causes cooling effect in the tobacco smoke and (+) isomer has no effect. Beetle pheromone activity of recemic mixture is higher than either of the enantiomers and 1% content of wrong enantiomer abolishes beetle pheromone activity. Stereoisomers resulting from restricted rotation about single bonds are called atropisomers, e.g. substituted biphenyls, BINAL-H. Stereoisomers resulting from rotation about single bonds are called rotamers. Water molecule: Van der Waals radius of 1.4 Å. Stereochemistry of Reaction: 1. Chemoselectivity: In a Bifunctional compound, a reagent reacts preferentially with only one functional group, e.g. selective reduction reaction, i.e., selective reducing agent, e.g., LiAH4. 2. Regioselectivity: A reagent attacks selectively from many possible sites of attack, e.g. more yield of meta product than ortho/para in aromatic substitution reactions. 3. Stereospecificity: Specific reaction of stereoisomeric reactant, i.e., each stereoisomer of a reactant reacts specifically to give different products. 4. Stereoselectivity: Selection between many possible stereoisomeric products, i.e., reagent leads selectivity to one of the many possible stereoisomeric products, e.g. Stereoisomer 1 --------------- P1(Major) + P2 Stereoisomer 2 --------------- P1 + P2(Major)  All stereospecific reactions are stereoselective.  Stereoselective reactions may or may not be stereospecific. Crams Rule: To predict major product. Felkin-Ahn modification: To predict major products. Sharpless Epoxidation: Reaction of acrylic alcohol with tertiary butylhydroperoxide, catalyzed by titanium tetraperoxide in the presence of (+) or (-) diethyl tartrate. Anti-Markovnikov’s rule: Presence of peroxide, e.g. only HBr. Sigmatropic Rearrangement:  Cope rearrangement [3,3]  Claisen rearrangement [3, 3] Cycloaddition reaction:  Diel’s – Alder reaction PHARMACEUTICAL INORGANIC CHEMISTRY GASTROINTESTINAL AGENTS:  Acidifying agent - Dil. Hydrochloric acid (HCl) for Rx of Achlorhydria - Dil. HCl contains 10 % w/w HCl.  Antacids - Sodium bicarbonate (Baking soda) - Aluminium hydroxide gel - Calcium carbonate (Precipitated chalk) - Magnesium carbonate - Magnesium trisilicate - Magnesium oxide (Milk of magnesia, i.e., MgO) - Magaldrate (Hydrated magnesium aluminate)  Protectives - Light kaolin - Heavy kaolin (China clay)  Cathartics (promote defecation) - Irritants - Hydrophilics / Saline / Osmotic laxatives - Emollients - Detergents Cathartics Magnesium sulphate Sodium sulphate Sodium potassium tartrate Name of the salt Epsom salt Glauber’s salt Rochelle salt / Seignette salt ELECTROLYTES Electrolytes are used in replacement therapy as in Replacement of Na+, K+, Ca++ Electrolyte combination therapy: - Compound Sodium chloride injection (Ringer’s solution) - Compound Sodium lactate injection (Ringer’s lactate / Hartmann’s solution) Hydrogen ion concentration in extracellular fluid is 4  10-8 Eq/l. Electrolytes used in Acid-Base therapy: - Potassium acetate Potassium citrate Sodium acetate Sodium bicarbonate Sodium citrate Sodium phosphate Ammonium chloride TOPICAL AGENTS Topical Agents Examples Protectives / Adsorbents Antimicrobial Astringents Talc (Magnesium + Aluminium silicate) Calamine (Zinc + Ferric oxide) Alum (Potassium aluminium sulphate) Zinc chloride, sulphate Sublimed suphur (Flowers of sulphur) Miscellaneous Antimicrobials: Compounds Oxidation mechanism Halogen mechanism Iodine & iodine preparation Protein precipitation Examples Hydrogen peroxide (H2O2) Chlorinated lime Aqueous iodine solution (Lugol’s solution) Povidone-iodine solution Boric acid, Borax, Silver nitrate Astringents Compounds that cause protein precipitation - Alum (Potassium aluminium sulphate) Zinc chloride, sulphate – Also used as ‘Emetic’ DENTAL PRODUCTS Apeutic value is related to dentrifices. Polishing agents: - Sodium fluoride Stannous fluoride Calcium carbonate Sodium meta-phosphate Desensitizing agents: - Strontium chloride Zinc chloride Potassium nitrate GASES AND VAPORS - Oxygen (O2) – 21% by volume of atmosphere Preparation: (i) (ii) By fractionation of liquid air By electrolysis of water EXPECTORANTS AND EMETICS Expectorants: - Ammonium chloride Ammonium acetate Ammonium carbonate Potassium iodide Emetics: - Tartar emetic – Antimony Potassium Tartrate Copper sulphate (CuSO4) and Zinc sulphate (ZnSO4) – Also used as emetic. ANTIOXIDANTS - Sulphur dioxide Sodium bisulphate Sodium metabisulphite Hypophosphorous sodium Sodium thiosulphate Sodium nitrite BUFFERS Buffer capacity: Amount, in Moles, of strong acid or strong base required to change pH of one litre of buffer solution, by one unit. Buffer Hydrochloric acid Acid phthalate Neutralised phthalate Phosphate Alkaline borate  pH 1.2 - 2.2 2.2 - 4.0 4.2 - 5.8 5.8 - 8.0 8.0 - 10.0 RADIOPHARMACEUTICALS - Radioactive elements – Thorium, Radium, Uranium - Unit of Radioactivity (Dosimetry) – Curie (Ci) & Becquerel (Bq) - Absorbed radiation – Roentgen - Exposed radiation – Rad 1 Curie = 3.7  1010 dps (disintegration per second) 1 Curie = 3.7  1010 Bq 1 Bq = 2.7  10-11 Ci