General and Organic Chemistry: Theory content HT 2016

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1 Department of Medical Biochemistry and Biophysics Bachelor's Programme in Biomedicine General and Organic Chemistry General and Organic Chemistry: Theory content HT 2016 Test: Laboratory techniques and safety. Lecture: Lab techniques and lab safety. Lab lecture: Introduction to the lab Lab compendium: Safety regulations, common work operations. Key concepts: Entire safety section. Reflux, drying agents, rotary evaporator, fractional distillation (with and without vacuum), recrystallization, melting point determination, desiccator, extraction, separation funnel, TLC. Lecture: Health risk assessment, classification and labelling. Introduction to health risk assessment. Hazard identification, hazard characterisation, exposure analysis, risk characterization. Application to various types of chemicals. Classification and labelling of chemicals. Criteria for classification. Individual chemicals and products. Handling on national, EU and global levels. Test 1. Lecture: Atomic structure. Periodic table. Inorganic Chemistry. Lecture: Chemical bonding. Polarity. Fessenden & Fessenden (F&F) ch , 1.6, 1.7E, Key concepts: Electron shell and orbitals, quantum numbers. Nobel gas structure. Aufbau principle, Hund's rule, the Pauli exclusion principle. Structure of the periodic table in general. Electronegativity. Inductive effect. Binding and anti-binding molecular orbitals. Delocalization of electrons. Electronic structure of diatomic molecules. Hybridization of C, O, N. Lewis formulas. Formal charge (oxidation number). Ionic bonding, hydrogen bonding, dipole interactions, van der Waals bonding. Polarity. Functional groups in organic chemistry. Lecture: Structural isomerism. Nomenclature. Alkanes. F&F ch. 1.5, , Key concepts: Chemical formulas. Saturated, unsaturated, linear, branched, cyclic hydrocarbons. Structural isomers. Hydrocarbons in Tab IUPAC nomenclature. Branched chain name. Nomenclature of alkanes, alkenes, alkynes, benzene, alcohols, aldehydes, ketones, carboxylic acids and all these substituted with halogens, nitro groups and phenyl groups. Hydrocarbon properties and use in organic chemistry. Conjugated double bonds, benzene, resonance structures. Lecture: Geometric isomerism. Conformations. Cyclohexane. Optical isomerism. F&F ch. 4 except 4.9D, 4.9E. Key concepts: E/Z, cis/trans (also cyclic). Equatorial/axial. Chair/boat-shape. Newman projections. Staggered, eclipsed, anti, gauche. Polarimeter. Fischer Projections. +/-, d/l, D/L, R/S. Racemic mixture, diastereomers, enantiomers. Erythro/threo/meso. Chirality and prochirality. 1

2 Lecture: Thermodynamics and kinetics. Key concepts: Equilibrium. Gibbs free energy, entropy, enthalpy. Exo-/endotherm, spontaneous reaction. Activated complex/transition state, activation energy. Velocity constant, reaction order. Catalysis. Lecture: Reactivity. Lecture: Alkyl halides, substitution, elimination. F&F ch D. Key concepts: Inductive effects, resonance effects, steric effects, exemplified and explained on acid strength. S N 1, S N 2, E1, E2: Definition, mechanism, energy diagram, speed, stereochemistry, what determines (structures, concentration, solvent, temperature). Basicity and nucleophilicity. Rearrangements. Saytzeff s rule. Lecture: Alcohols, Grignard reactions. Lecture: Ethers, epoxides, sulphides. F&F ch , ch. 8 except 8.5. Key concepts: Classification and synthesis of alcohols. Grignard reactions. Substitution, elimination, esterification of alcohols. Ethers and epoxides: synthesis and substitution reactions. Thiols, sulphides, sulphoxides (chirality), sulphones. Lecture: Basic chromatography and distillation. Lab compendium: Analysis methodology: GC (just theory), TLC. Key concepts: Partition chromatography, partition coefficient. Stationary and mobile phase. Chromatography based on adsorption, distribution, ion exchange, gel filtration, affinity. Column chromatography, TLC. Boiling point diagrams, azeotropes. Colligative properties of osmotic pressure. Test 2. Lecture: Alkenes, alkynes, addition. F&F ch. 10.1, 10.5, 10.6, 10.7, 10.9A, 10.9C, 10.10, before A, 10.12B. Key concepts: Acetylide ion, electrophilic addition reaction, Markovnikov's rule. Anti- Markovnikov addition. Addition of H 2 O, H 2 SO 4, borane, halogens. Halohydrins. Hydrogenation, stereochemistry. Lecture: Aldehydes, ketones. F&F ch , C, 13.8, Key concepts: The carbonyl group. Aldehydes and ketones: nomenclature, preparation and reactions. Derivatives: acetals, cyanohydrins, imines, aldol products. Concept of protecting group. Lecture: Carbohydrates. F&F ch. 23 (except 23.6D, 23.10). Key concepts: Carbohydrates in Fig 23.1 (formula; glucose, fructose, galactose, ribose). Configurations, cyclization (including mechanism), furanose and pyranose, Fischer and Haworth projections, epimers, diastereomers, enantiomers, anomers, mutarotation. Glycosides: principle and mechanism. Ketose-aldose conversion; fundamental structure of aldonic acids, aldaric acids, uronic acids, alditols, not mechanism. Disaccharides: fundamental structure (bonds between monosaccharides), no examples. 2

3 Lecture: Carboxylic acids, carboxylic acid derivatives. Lecture: Condensation. F&F ch. 14.1, , 14.8B-C, 15.1, 15.3B, 15.3C up to (incl.) "Reaction with organometallic compounds" (page ), 15.4B, 15.4C. 15.5B, 15.5C, 15.6, 15.8B, 15.8C (not NMR), 15.11D, , 17.6, 17.7B, 17.8, Key concepts: The carboxyl group. Carboxylic acids: nomenclature, English trivial names, production, oxidation and reduction. Factors affecting the pk a. Derivatives of carboxylic acids and their preparation and reactions. Carbonyl compounds four reactions types: 1) Nucleophilic addition: mechanisms of hydration, formation of cyanohydrins, imines, acetals. 2) Nucleophilic acyl substitution: mechanisms of formation of acid halide, ester formation, ester hydrolysis, transalkylationtransesterification. 3) - Substitution: formation of enolate. -halogenation. -alkylation with diethyl malonate or ethyl acetoacetate. Decarboxylation. -alkylation of ketones. 4) Condensation reactions: Aldol condensation, intramolecular aldol condensation. Claisen condensation, intramolecular Claisenkondensation. Lecture: Chromatographic applications. Berg, Stryer, Tymoczko (Berg) p (This is from the recommended literature Biochemistry by Berg, Stryer, Tymoczko; here only partially relevant) Key concepts: HPLC design and mode of action, columns, detectors. Isocratic and gradient elution HPLC. Derivatisations. Lecture: IR, UV. F&F ch , 10.3A, 13.3A, 14.2A, Lab compendium: Analysis methodology: IR spectroscopy; IR interpretation. Lab compendium: IR and UV spectroscopy. Key concepts: Wavelength, frequency, wave number. IR: Origin of IR spectra, stretching & bending. Fingerprint region. Characteristics of alcohols, amines, carbonyl compounds. UV: Electron transfers. Absorbance. Electron transitions in conjugated systems by UV absorption. Test 3. Lecture: Aromatic compounds, benzene. Electrophilic substitution. F&F ch A, 11.8C Key concepts: Electronic structure of benzene. Aromaticity, Hückel's rule, cyclopentadiene ions. Electrophilic aromatic substitution, mechanism, halogenation, nitration, alkylation, Friedel-Crafts alkylation and acylation, sulphonation. Second substitution: activating, deactivating, directing groups. Mechanism. Lecture: NMR. F&F ch , 9.12 before 9.12A, 10.3B, 11.2B, 13.3B, 14.2B. Lab compendium: NMR interpretation. Key concepts: Origin of NMR spectra, resonance. Downfield/upfield, shielded/deshielded. Chemical shift. Inductive and anisotropic effects. Magnetically and non-magnetically equivalent protons, how to count protons. Spin-spin coupling, splitting, chemical exchange. Practical interpretation of simple 1 H-NMR spectra. 13 C-NMR. Lecture: Oxidation, reduction. 3

4 F&F ch. 7.8A, 7.8C, 10.13, 13.6B, 13.6D, 13.7, 18.4B, 23.6, Key concepts: The terms oxidation and reduction. Peroxide. 3 methods incl. mechanisms for reduction: 1) hydrogenation, 2) metal hydrides, 3) metals in ethanol or liquid ammonia. 4 methods incl. mechanisms for oxidation: 1) KMnO 4, 2) CrO 3, 3) peroxy acids, 4) ozone incl. 3 2 methods of treatment of ozonoide. Lecture: Radioactivity, stable isotopes, labelling. Compendium "Radioactivity, stable isotopes, labelling". Key concepts: Carbon and hydrogen isotopes. Decay by, -, +, electron capture. Radiation,,,, X-ray. Radioactive decay law, units of radioactivity. Synthetic routes for the incorporation of H-and C-isotopes. Measurement methods incl. GM tubes, liquid scintillation counter in detail. Efficiency, quenching, measurement of different isotopes simultaneously. Lecture: Amines and amino acids. F&F ch A only Reaction of amines and alkyl halides, 18.4B, 18.5, 18.6, 18.8, 25.1, 25.2 (except Gabriel phtalimide synthesis ), 25.3B, 25.3C, 25.5, 25.7 before A. Key concepts amines: Nomenclature. Hybridization. Preparation 1) from halides, 2) by reducing a) nitro-compounds, b) nitriles, c) imines (reductive amination). Reactions: 1) acid base relationship, factors affecting base strength, 2 ) alkylation with RX, 3) acylation with acid chloride, 4) reaction with aldehydes or ketones, 5) diazotization with nitrite + strong acid; mechanisms. The use of "phase-transfer reactions". Key concepts amino acids: General structure of natural amino acids. Structures of glycine, alanine, histidine, tryptophan. Zwitterions. Side chains acid-base properties. Preparation: 1) aldehyde + ammonia + cyanide (Strecker synthesis), 2) substitution of -halo acids, 3) reductive amination of -keto acids. Reactions: 1) peptide bond formation and protecting groups in principle - tboc protective group as example. Peptide bond properties. 2) Reaction with ninhydrin. Lecture: Gas chromatography, mass spectrometry. F&F ch (Berg page 93-95) Lab compendium: Analysis methodology: Gas Chromatography; MS interpretation. Key concepts: gas chromatograph design and function, columns, detectors. Isothermal and temperature-programmed analysis. Derivatisations. Mass spectrometer design and function: ionization (EI, MALDI, ESI), analysers, detectors. Appearance of mass spectra (EI). Interpretation of the EI-MS spectrum. MS of macromolecules. Lecture: Radical Reactions. Reactive oxygen species. F&F ch B, 6.5, 6.6B, 6.7, 6.8 up to (excl.) 6.8A. Compendium "Radical Reactions Key concepts: homolytic and heterolytic cleavage. Bond dissociation energy (BDE). Hybridization and stabilization of carbon-centred radicals. Mechanism of free radical chlorination incl. energy considerations and energy diagram. Reactivity of the other halogens. The phenomenon of selectivity and how Hammond's postulate explains the selectivity of the bromination. The use of NBS for bromination; mechanism. Electronic structure of oxygen in the ground state. Autooxidation of various compounds. Antioxidants. The 4 different "reactive oxygen species" - what are they and how/where they are formed. Oxidation of biomolecules due to reactive oxygen species; oxidative stress. Lecture: Polycyclic and heterocyclic compounds, cyclic lipids. 4

5 F&F ch. 19.1, 19.2, 19.6 incl. table 19.1, 19.7 up to (excl.) A, 19.9 up to (incl.)a. 24.4, A. Key concepts: Examples of common poly-and heterocyclic compounds. Heterocyclic compounds: structures of pyridine, imidazole, pyrimidine, purine, pyrrole, indole, furan, and pyran. Structure of pyrrole and pyridine; implications for base strength and reactivity (EAS). Formula (incl. carbon numbering) and 4 functions of cholesterol., -substituents and axial/equatorial substituents. General structure of prostaglandins. Lecture: Enzyme mechanisms. Berg , (9.4). Enzymes as catalysts, thermodynamic explanation. Active site, transition state. Lock-and-key, induced fit. General catalysis. Principles of enzyme mechanisms of serine proteases, carbonic anhydrase and kinases. Not in tests (but included in the final exam) Lecture: Introduction to Medicinal Chemistry. Connection between structure and pharmacological effect of major drug groups, their chemical properties. Physical-chemical properties influence on bioavailability. Lecture: Principles of modern drug design. Principles of drug design, the Swedish pharmaceutical industry. Lecture: Drug development. Combinatorial chemistry, high-throughput chemistry, computational chemistry, solid phase synthesis. Lecture: Chemical carcinogenesis and PAHs. Mechanisms and tests for genotoxicity and chemical carcinogenicity. Polycyclic aromatic hydrocarbons (PAHs). Importance of molecular structure and chemical properties for exposure and toxicity. Exposure to PAHs. Health risks of PAH. Lecture: The syntheses of short-lived isotopes, PET. Synthetic routes for the incorporation of H and C isotopes, the synthesis of short-and long-lived isotopes. Principle of PET camera. F&F Appendix: Nomenclature of organic compounds. Changed : :44, BLo 5