Once the reaction was complete, 20 drops of distilled water was cautiously added to the mixture followed by 20 ml of distilled water. The solution was cooled on an ice bath until aspirin crystallized. In event of no crystal formation, the walls of the flask were scratched with a stirring rod to initiate crystallization. The crystals were filterer using a Buchner filter and extracted using chilled water.
The experiment was repeated in a microwave oven and the yield was compared. Different types of receptors. Enzyme kinetics and inhibition. Enzyme inhibitors as drugs - irreversible, competitive and non-competitive inhibitors.
Drug access, lipophilicity, metabolism, drug formation, synthesis of analogues and prodrugs such as aspirin and paracetamol. Sympathetic nervous system, a, b1, b2 receptors. Isoprenaline as lead compound. Development of pronethalol, propranolol and cardiosselective b- blockers such as practolol. Development of salbutamol as a selective b2-stimulant bronchodilator. Histamine receptors, discovery of cimetidine and ranitidine as H2-receptor histamine antagonists.
Synthesis, chemistry and spectroscopy of these anti- ulcer drugs. Know about the discovery and chemical modification of lead compounds and structure activity relationships. Be able to describe how morphine was modified to produce useful analgesics. Know about the synthesis and biological activity of kappa-selective opioids. Be able to discuss the importance of combinatorial chemistry.
Know about the evolution of the anti-inflammatory steroids. Be able to discuss the search for disease modifying anti-rheumatoid drugs. Know about research on the neuromuscular blocking agents culminating in the development of pancuronium bromide Pavulon. Be able to discuss the development of improved neuromuscular blocking agents typified by vecuronium bromide Nurcuron and rocuronium bromide Esmeron. Outline: Relationships between physical properties of organic compounds and biological activity, structure activity relationships, discovery and modification of lead compounds, drug design and combinatorial chemistry.
Clinical use and limitations of morphine, chemical modifications, agonist vs. Multiple opioid receptors including kappa, developed of initial leads by synthesis, importance of stereochemistry on biological activity. Need for combinatorial methods, solid phase peptide synthesis, peptide libraries, solid phase synthesis of benzodiazepines. Structures, source and biochemistry of endogenous corticosteroids, structural modifications to increase potency and reduce side effects.
Pathogenic mechanisms involved in the auto immune diseases such as rheumatoid arthritis and methods of modulating them.
Synthesis and biological activity of a novel steroidal potentially disease-modifying anti-rheumatoid drug. Design and synthesis of non-steroidal anti-inflammatory agents by pharmacophoric pattern searching. Natural sources of steroids and their conversion into useful intermediates. Mode of action, design, synthesis and structure activity relationships of neuromuscular blocking agents. Advantages and disadvantages of Pavulon, Norcuron and Esmeron.
Title: Advanced Organic Synthesis Lecturer s : Prof G W Kirby Aims: To develop a logical and rational approach to the synthesis of complex organic molecules, building on students' previously gathered knowledge and information. Recall examples of reaction types, mechanisms, and protecting groups from other lecture courses. Understand, using simple examples, how these are applied in synthetic sequences.
Understand the concept of retrosynthesis. Relate retrosynthesis to the planning and execution of some syntheses. Understand illustrated examples of synthesis which concentrate on conceptual design and principles of synthesis and reinforce latent knowledge. Develop the above protocol to more complex examples. Develop confidence in your ability to cope with problems in synthesis. Outline: This course, following on earlier student exposure to synthetic methods, is targetted at the rational design of complex molecule synthesis.
The basis, the disconnective retrosynthetic approach, emphasises functional group protection and interactions, mechanistic stereoelectronics and structural and stereochemical architectural problems.
The ideas all ullustrated by syntheses of specific target molecules, e. Discuss the variety of biological molecules and describe the properties of amino acids, peptides and proteins. Discuss methods of separation and purification of proteins and techniques for the determination of molecular weight and amino acid sequencing.
Discuss the study of protein conformation using spectroscopic and diffraction techniques. Discuss the binding of ligands to macromolecules, enzyme kinetics and molecular dynamics. Use information provided to discuss topics concerning the structure, function, and characterisation of proteins and other biological macromolecules.
Outline: This course of lectures will introduce some physical chemistry aspects of biological molecules. The nature of biological molecules; the properties of amino acids, peptides and proteins; methods of purification: salt fractionation, chromatography, electrophesis; methods forestablishing molecular weight; determination of the composition of proteins: amino acid analysis, amino sequencing; sequencing at the DNA level; immunological methods of detection; UV absorption spectroscopy: effects of pH, polarity, etc.
Title: Reactivity of Transition Metal Organometallic Compounds Lecturer s : Dr L J Farrugia Aims: To understand some of the basic reactions of organic ligands which are coordinated to transition metals, and how certain ligands may be stabilised upon coordination.
Understand the bonding in, and types of compounds formed by the cyclopentadienyl ligand; know about the electrophilic substitution and metallation reactions of ferrocene. Know some examples of the differing substitution rates in dienyl versus cyclopentadienyl compounds and the reasons and evidence for ring slippage. Understand how some unstable and non-existent molecules are stabilised by coordination to transition metals; know some examples such as cyclobutadiene and trimethylene methane.
Know how both Fischer and Schrock carbenes are made and the reasons for their different reactivities. Outline: Metallocenes and revision of bonding therein; versatility of the C5H5 ligand - occurrence in both high and low oxidation state compounds; half sandwich compounds, bent metallocenes and triple decker sandwiches; structure and syntheses of main group analogues of Cp such P5, As5, C4H4P, C4H4BMe, etc.
Stabilisation of unstable molecules such as cyclobutadiene, trimethylene methane, benzyne and Bi2 by co-ordination to transition metals. Nucleophilic attack at CO, the formation of Fischer carbenes; nucleophilic reactions of the Fischer carbene; synthesis of Shrock carbenes, and the reason for their different reactivity. Title: Aromatic Systems Lecturer s : Dr P H McCabe Aims: To appreciate the variability of aromatic character and reactivity within benzene derivatives, non-benzenoid carbocycles neutral or charged and heterocycles; to be aware of general synthetic routes to simple heterocycles; to be able to apply this knowledge to unfamiliar cases.
Be able to recognise aromatic structures by simple p-electron counting. Be familiar with selected spectroscopic characteristics of aromatics. Be familiar with the range of electrophilic substitution reactions and of addition, elimination, nucleophilic and radical reactions of carbocyclic aromatics and heterocycles. Be familiar with the general syntheses and reactivity of furans, pyrroles, thiophenes, imidazoles, indoles, pyridines, quinolines, isoquinolines, diazines and purines.
Benzene, -, -, annulenes. Diagmagnetic ring current. Chemical shift of outside and inside hydrogens. Benzene rectivity and selected reactivity of annulenes. Cyclopropenium, cyclobutadiene dication, cyclopentadienide anion, tropylium.
Furan, pyrrole and thiophene. Paal-knorr synthesis. Fischer synthesis. Electrophilic and nucleophilic substitution, Chichibabin reaction. Pyridine and pyrimidine. Hantzsch and Traube syntheses. Pyridine N-oxide.
Syntheses of quinoline Skraup , isoquinoline Bischler-Napieralski and reactivity. Understand the genetic theory of organisms and how information can be held in molecules. Understand with examples the linkage systems in oligo and poly-sacchardes.
Understand in formal terms how genetic information in DNA molecules replicates, and the formal relationship between genes and protein molecules. See the need for a genetic code in translating information from nucleic acids to protein, and to understand at a simple level the roles of messenger, transfer, and ribosomal RNA in these processes. Understand the terms primary, secondary, and tertiary structures in proteins.
Appreciate the limited yet varied character of the amino acid set, and the enormous variety of possible proteins. Discuss the physiochemical factors controlling the secondary and tertiary folding of polypeptide chains in proteins. Discuss, with examples, some of the factors thought to account for enzyme action. Be able to provide plausible mechanisims for three enzyme catalysed reaction types. Title: Statistical Thermodynamics Lecturer s : Dr J H Dymond Aims: To show how equilibrium thermodynamic property data for dilute gases and solids, and chemical reaction rates, can be related to properties of the individual molecules Objectives: 1.
Derive the number of ways of distributing n indistinguishable particles among g degenerate energy states. Give the corrected Boltzmann statistics for the total number of arrangements of N particles, where ni are in energy level ei which has a degeneracy gi 3.
State the Boltzmann distribution law, and use it to determine the relative populations of different energy levels. Appreciate the meaning and importance of the molecular partition function, and relate it to the total energy of a system. Factorise the molecular partition function.
Give the expression for the translational partition function, and hence the contribution to the energy and heat capacity at constant volume for an ideal gas 7.
Give a statistical thermodynamic explanation for ideal gas expansion at constant temperature. Appreciate the impossibility of obtaining absolute energies. Give the expression for the rotational partition function, and know the meaning of the characteristic rotational temperature and the symmetry number. Give the contribution to the energy and heat capacity at constant volume from rotational motion. Give the expression for the vibrational partition function, and know the meaning of the characteristic vibrational temperature.
Calculate the contribution to the energy and heat capacity at constant volume arising from vibrational motion. You can use some of the filtrate to rinse the Erlenmeyer flask if necessary. Rinse the crystals several times with small portions 5 mL of cold water and air dry the crystals on a Buchner funnel by suction until the crystals appear to be free of solvent.
Test this crude product for the presence of unreacted salicylic acid using the ferric chloride test. Record the weight of the crude solid which probably contains water. Filter the solution through a Buchner funnel to remove any insoluble impurities or polymers that may have been formed. Wash the beaker and the funnel with 5 to 10 mL of water. Carefully pour the filtrate with stirring, a small amount at a time, into an ice cold HCl solution ca 3. HCl in 10 mL of water in a mL beaker and cool the mixture in an ice bath.
Make sure that the resulting solution is acidic blue litmus paper and that the aspirin has completely precipitated out. Filter the solid by suction and wash the crystals 3X with 5 mL of cold water each. Remove all the liquid from the crystals by pressing with a clean stopper or cork. Air dry the crystals and transfer them to a watch glass to dry. Test a small amount of the product for the presence of unreacted salicylic acid using the ferric chloride solution. Dissolve the final product in a minimum amount no more than mL of hot ethyl acetate in a 25 mL Erlenmeyer flask.
Make sure that the product is completely dissolved while gently and continuously heating on a steam bath.Procedure: 1. It is assumed that the student has completed the relevant first, second and third year courses on inorganic chemistry. The synthesis reaction of aspirin is shown below: Since acetic acid is very soluble in water, it is easily separated from the aspirin product.
The maximum allowable amount of free salicylic acid in an aspirin sample is 0. Describe how the stereochemistry features of alcohol dehydrogenase reactions were established. If acetylsalicylic acid does not begin to crystallize out, scratch the walls of the flask with a glass rod. Be able to provide plausible mechanisims for three enzyme catalysed reaction types.
Be able to discuss the importance of combinatorial chemistry. Excimer lasers and super-radiance. Synthesis and biological activity of a novel steroidal potentially disease-modifying anti-rheumatoid drug. Describe the relationship of Slater-type orbitals and Gaussian-type atomic functions to hydrogenic wavefunctions.
Ways of achieving population inversions. Sympathetic nervous system, a, b1, b2 receptors.