Module Information For Visiting and Erasmus Students 2014/15 School* Module Code* Chemistry CH3103 ORGANOMETALLICS & COORDINATION CHEMISTRY Module Name* ECTS Weighting* 5 Semester/term Semester 1 taught* Contact Hours* 33 Hours Module Prof. Bob Baker, Prof. Sylvia Draper, Prof. Yurri Gu’nko Personnel Learning Outcomes Understand the basics of organometallic chemistry • Understand the structure-reactivity relationships for selected metals in each group of ligands • Understand the differences in ligand structures and how these influence the reactivity of the transition metal The subject of this course is the electronic spectroscopy of transition metal complexes, as observed by UV-visible spectroscopy. The aim of the course is to develop an understanding of: The absorption of light and the mechanism by which this leads to electronic rearrangement in a transition metal complex The implications that this has for the origin of the wide-ranging and characteristic colours of coordination complexes. The importance of both the wavelength and intensity of the light absorbed in determining the nature of the transitions between electronic energy levels. The influence of the metal oxidation state, the nature of the ligand and the coordination number and geometry of the complex on its electronic properties. The application of UV-visible absorption spectroscopy and the effective interpretation of spectra. It also develops skills in the manipulation of data and in analysing spectra Students will learn main principles of homogeneous catalysis by TM complexes, mechanisms and catalytic cycles. Module Learning Aims To learn main principles of homogeneous catalysis by TM complexes, mechanisms and catalytic cycles. Organometallics (Prof. Y.K. Gun’ko): Module Content/ Description* 9 lectures and 2 tutorials covering: Introduction, Main definitions, Importance of Organometallic Chemistry: Industrial Applications. Organometallic Chemistry of the Main Group Elements General Synthetic Approaches in Main Group Organometallics. Chemistry of Alkali Metals Chemistry of Alkali Earth Metals Chemistry of 12th Group of the Periodic Table Chemistry of 13th Group of the Periodic Table Chemistry of 14th Group of the Periodic Table E-E multiple bonding (E = main group element) Organometallic Chemistry of the Transition Metals Definition and classification of TM Organometallic compounds. Organometallic Chemistry of 1-ligands (alkyl, aryl and carbonyl) Organometallic Chemistry of 2-ligands (alkenyl) Organometallic Chemistry of 3-ligands (allyl) Organometallic Chemistry of 4-ligands (di-ene and cyclobutadiene) Organometallic Chemistry of 5-ligands (Cp) Organometallic Chemistry of 6-ligands (Arenes) Each species is examined in turn, detailing their synthesis, properties characteristic reactions and applications Transition metal compounds and complexes (Prof. Sylvia Draper): 9 lectures and 2 tutorials covering: Lecture 1 Definitions and concepts; What is electronic spectroscopy? Absorption of light by transition Metal Complexes; Limits of Ligand Field Theory – interelectron repulsion; Microstates; Russell-Saunders Coupling Lecture 2 Tutorial; Revision of quantum numbers and Pauli Principle; Formation of microstates in metal ions; Generation of term symbols; Assignment of Ground state term symbols Lecture 3 Cystal Field Splitting on Free ion terms; Orgel Diagrams for weak field ligand complexes d1, d4, d6, d9 d2, d3, d7, d8 Lecture 4 Orgel Diagrams continued and Interpretation of weak field spectra Quantum mixing; Calculation of quantum mixing term x and Racah parameter Lecture 5 Nephelauxetic effect; d5 – orgel diagram and spectra; Spin and Lapporte Selection Rules; Spectrochemical Series Lecture 6 Overview and Consequence of Selection Rules; Understanding and reasons for the broadening of electronic Transitions; Molecular Vibrations, spin-orbit coupling, JahnTeller distortion Lecture 7 Problem-base exercises combing electronic and magnetic data; Using Orgel Diagrams Lecture 8 and 9 Tanube-Sugano Diagrams; High-spin/Low spin transition Calculation of octahedral splitting, E and B d0 and d10 ions –charge transfer transitions; Continuation of problem based exercises using Tanube Sugano Diagrams Inorganic reactions mechanism and homogenous catalysis (Prof. Robert Baker): 9 lectures and 2 tutorials covering: 1. Comparison of Homogeneous and Heterogeneous catalysts, Features of Transition Metal Catalysts: Bonding ability; Ligand variety; Ligand effects. 2. Features of Transition Metal Catalysts: Variability of oxidation state, Variability of coordination number, The eighteen electron rule, Solutions to tutorial on the 18 e- rule. 3. Stage 1: Assembly: Transmetallation; Substitution/Addition reactions; substitution of a 2 edonor; addition of a 2 e- donor; Oxidative Addition 4. 2 e- oxidative addition continued; Modification; Migratory Insertion Reactions; 1,1migratory insertion; 1,2-migratory insertion; Nucleophilic attack on alkenes. 5. Stage 3: Expulsion: 1,1-reductive elimination; Hydride elimination; beta-hydride elimination; alpha-hydride elimination; Catalytic Cycles: Hydrogenation with Wilkinson's catalyst. 6. C-C bond formation: Pd-catalysed cross coupling, Hydroformylation by the Oxo-process. 7. Hydroformylation, Wacker Process, BP(Monsanto) acetic acid process. 8.Tennessee-Eastman acetic anhydride process, Shell Higher Olefin Process. 9.Ziegler-Natta ethylene oligomerisation, Kaminsky catalyst, Asymmetric hydrogenation: catalyst and mechanism for asymmetric synthesis of L-dopa. Recommended Reading List Organometallics – A Concise Introduction – Ch. Elschenbroich, A. Salzer, 1st edition, VCH, Weinheim, 1989. Cotton, Wilkinson, Murillo, Bochmann, Advanced Inorganic Chemistry, 6th Ed R. Whyman, Applied Organometallic Chemistry and Catalysis, Oxford Chemistry Primers Module Pre N/A Requisite Module Co N/A Requisite Assessment Annual examination Details* Module Code* Module Name* ECTS Weighting* CH3104 SOLID STATE MATERIALS 5 Semester/term Semester 2 taught* Contact Hours* 33 Hours of Lectures Module Prof. Yurri Gun’ko, Prof. Graeme Watson, Prof. Wolfgang Schmitt Personnel Learning Outcomes Module Learning Aims After this course students will be able describe types, synthesis, properties, structures and applications of main inorganic polymers including boron and aluminium containing polymers: borates, borides, B-N systems, carboranes, aluminoxanes. Silicon-containing polymers: silicates and alumosilicates (zeolites), polysilanes, polisiloxanes, polisilazanes and polysilazoxanes. N,-P- and Scontaining polymers: phosphates, P-N systems, polymeric sulphur, S-N compounds and polymers. Organometallic and coordination polymers To learn types, synthesis, properties, structures and applications of main inorganic polymers Inorganic Polymers (Prof. Yurii Gun'Ko) Module Content/ Description* 9 lectures and 2 tutorials covering: Main definitions and comparison of organic and inorganic polymers. Homo- and heterocatenation; survey of catenation in the Periodic Table. Characterisation and evaluation of inorganic polymers. Boron and aluminium containing polymers: borates, borides, B-N systems, carboranes, aluminoxanes. Silicon-containing polymers: silicates and alumosilicates (zeolites), polysilanes, polisiloxanes, polisilazanes and polysilazoxanes. N,-P- and S- containing polymers: phosphates, P-N systems, polymeric sulphur, S-N compounds and polymers. Organometallic and coordination polymers. Inorganic-organic hybrid polymeric materials. Structural Inorganic Chemistry (Prof. Wolfgang Schmitt) 9 lectures and 2 tutorials covering: - Description of chemical structures. Solid state structures seen as arrays of linked polyhedra and as sphere packings with occupied interstices; - Structure of the metals; element structures of the non-metals (halogens; chalcogens, carbon, boron). - Polymorphism and phase transitions; - The interplay of chemical bonding/energy and structure; Factors governing the structure of ionic compounds, molecules and metals; Chemical bonding in solids: band theory; Peierls distortion; - Structural chemistry of the major solid state families: diamond-type structures (diamondtype structures under pressure); spinells; perovskites; oxides; halides; silicates and zeolites; NiAs and NaCl structure; rutile structure; SiO2 structures; - Structure and properties of semiconductor materials; - Structural principles of polyanionic, polycationic and cluster compounds; Wade rules, PSEPT rules; EAN rule; Klemm-Zintel-Bussmann; Isolobal principle; metal clusters and their applications; - Zintl and Chevrel phases; intermetallic phases - Properties of solids (e.g. Introduction to electronic, magnetic, piezoelectric and ferroelectric properties); - Symmetry as an ordering principle of crystal structures. - Metal-organic frameworks and reticular synthesis concepts; Synthetic methodologies and characterisation techniques of solid state materials: Synthesis: -Solid State Reactions (Area of contact between reacting solids, diffusion processes, the rate of nucleation of the product phase) -Steps in Conventional Solid State Synthesis - Solid state preparative methods, including chimie douce, sol-gel and vapour phase deposition. - Examples of syntheses of advanced materials with novel properties and potential applications including: Solid Electrolytes, Mixed Ionic/Electronic Conductors, Intercalation Materials and their applications (eg. Solid State Batteries, Fuel Cells and Gas Sensors); -Crystal defects, eg. interstitials, vacancies, dislocations, shear structures and solid-state solution doping mechanisms. Characterization: - Diffraction methods: crystal systems and Bravais Lattices - space group notation and space group diagrams. Bragg's Law in reciprocal space . Space group extinctions. Indexation of reflections. Scattering factors. Fourier Synthesis. The phase problem. The Patterson function and the direct method- structure refinement. Synchrotron Sources. Instrumentation. - The principles of EXAFS and its use as a structural technique - the interpretation of an EXAFS spectrum. -Introduction into electron microscopy (SEM and TEM) characterization techniques; possibly AFM and STM techniques; Solid state NMR and Raman spectroscopy (if not discussed in CH3015) Possibly if time permits or if not subject in SS): - Relationship between crystal structure, defect structure, composition and properties - as applied to a wide range of materials, with useful magnetic, electrical and optical properties (extends concepts discussed in Structural Inorganic Chemistry), lasers and smart windows. Recommended Reading List N. N. Greenwood and A.E. Earnshaw, Chemistry of the Elements, 1st or 2nd edition. J.E. Huheey, Inorganic Chemistry, 3rd and later editions. Inorganic and Organometallic Polymers, 1988, ACS, Washington, editors: M. Zeldin, K.J. Wynne, H.R. Allcock Inorganic Materials, 2nd edition, 1996, J. Wiley &Sons, edited by D.W. Bruce and D. O’Hare. Inorganic and Organometallic polymers, 2005, Springer Berlin Heidelberg New York, By Vadapalli Chandrasekhar Module Pre N/A Requisite Module Co N/A Requisite Assessment Annual Examination Details* Module Code* CH3203 Module Name* SYNTHETIC ORGANIC CHEMISTRY I ECTS Weighting* 5 Semester/term Semester 1 taught* 33 Hours Contact Hours* Module Personnel Learning Outcomes Module Learning Aims Prof. Mike Southern, Prof. Stephen Connon To understand the basic mechanisms and uses of metal-catalyzed reactions in synthetic chemistry Being able to analyze pericyclic reactions based on orbital considerations Understanding the basic reaction mechanisms of transition metal catalyzed reactions. Being able to apply a repertoire of organometallic reactions to synthetic problems. nic materials (coordination compounds). Organometallic C-C couplings Module Content/ Description* 9 lectures and 2 tutorials covering: Pd: Heck-, Suzuki-, Stille-, NEgishi-, Kumada- and Hiyma-couplings; Sonogashira and Trost-Tsuji reaction Ni: variations of the Pd(0) coupling; [4+4] cycloaddition Zn: Reformatsky reaction; Simmons-Smith cyclopropanation Cu: Gilman reagents and other organocuprates; Ullman coupling; Huisgen Cu(I) click chemistry Ru/Mo: Olefin metathesis; Grubbs catalysts; Schrock catalysts Co: Pauson-Khand reaction; Nicholas reaction Rh: Rhodium carbenoid insertion reactions Pericyclic Reactions and FMO Theory (Prof. Mike Southern) 15 lectures and 2 tutorials covering: Recap basic orbital theory FMO theory: simple MO theory, quantum chemistry of HOMO and LUMO. Orbital coefficients Suprafacial-suprafacial interactions: simple cases, comparison thermal and photochemical reactions, Woodward-Hoffman rules. Examples: [2+2], [3+2], [4+2] cycloadditions, Cheleotropic reactions Electrocyclic reactions: ring-closing reactions, con- and disrotatory reactions Sigmatropic rearrangements: [3,3]-sigmatropic rearrangements: Cope, Claisen, diazaCope, Johnson [2,3]-sigmatropic rearrangements: Wittig-Still, Stevens [1,3]- and [1,5]-alkyl/hydride shifts Stereoelectronic effects: FMO explanation of basic organic reactions Baldwin's rules Thorpe-Ingold effect Non-benzoid aromatic systems Physical Organic Chemistry (Prof. Stephen Connon) 9 lectures and 2 tutorials covering: Potential energy surfaces Thermodynamics of activated complex formation Hammett equation and its application Steric effects and Taft equation Proton-transfer reactions Hammond postulate Isotope effects Recommended Reading List C. Elschenbroich, Organometallics, Wiley-VCH G. Spessard, G. L. Miessler, Organometallic Chemistry, Oxofrd University Press, 2009 R. B. Woodward, R. Hoffman, The Conservation of Orbital Symmetry, Academic Press, 1970. I. Fleming, Molecular Orbitals and Organic Chemistry, Wiley, 2010. E. V. Anslyn, D. A. Dougherty, Modern Physical Organic Chemistry, University Science, 2005. Module Pre N/A Requisite Module Co N/A Requisite Assessment Details* Annual Examination CH3204 Module Code* SYNTHETIC ORGANIC CHEMISTRY II Module Name* ECTS Weighting* 5 Semester/term taught* Contact Hours* Semester 2 33 Hours Module Prof. Thorri Gunnlaugsson, Personnel Understanding the different reactivities of organoheteroatom compounds Learning • Being able to use organoheteroatom compouonds in complex syntheses Outcomes • Understanding the mechanistis aspects of rearrangement reactions • Understanding the reactivity of basic platonic hydrocarbon systems • Being able to use induced rearrangement reactions in total synthesis Module Learning Aims Introduction to heteroatom organic chemistry. Understanding the reactivity of organo-P, -S, -Si, -B, -SN systems. Carbocation structure and reactivity and use in chemical synthesis. Appreciating scientific discourse in chemistry. Heterocyclic Chemistry (Prof. Thorri Gunnlaugsson) Module Content/ Description* 9 lectures and 2 tutorials covering: Five-membered rings: Pyrrole: natural systems, Paal-Knorr synthesis, SEAr, C2 versus C3 substitution, basic reactions (Vilsmeier, Mannich, Michael) Furan: natural systems, Knorr synthesis, reactivity Thiophene: Indole: natural systems, Fischer indole synthesis Systems with more than one heteroatom Imidazole: Thiazole: Stetter reaction Six-membered ring systems Biological systems Pyridine syntheses Pyridine reactions Quinolines and isoquinolines Organoheteroatom Chemistry (Prof. Matthias Senge) 15 lectures and 2 tutorials covering: Organoheteroatom systems: P: Organophosphorous compounds. Scope and mechanism of Wittig reaction, ylides, Horner-Wadsworth Emmons reaction, Mitsonobu reaction, Staudinger reaction. Natural products and chemical warfare agents. Si: Organosilicon compounds. Electronic, structural and energetic aspects of the Si–C bond. Silyl ether as protecting groups. -Silyl effect. Chemistry of silanes, alkynyl and vinyl silanes. Peterson olefination reaction. S: Organosulfur compounds. Thiol chemistry and reactivity. Sulfides. 1,3-Dithianes in Umpolung reactions. Sulfoxides and sulfones; extrusion reactions. Julia olefination. B: Organoboranes. Hydroboration and reagents. Allylboranes. Sn: Organostannanes. Comparison C-Si and C-Sn chemistry. Use of R3SnH in synthesis. Carbocations and rearrangements Carbocation structure and electronic effects. Wagner-Meerwein rearrangement. Carbocations and regioselectivity: Zaitsev dn Bredt's rule. Classical and nonclassical carbenium ions, history of Winstein-Brown debate. Superacids. Nametkin, pinacol, and semipinacol rearrangement reactions. Tiffenau-Demjanov reaction. Hydride shifts. Anion-induced rearrangements: Favorskii, Ramberg-Bäcklund, benzylic acid. Carbene-induced rearrangements: Wolff, Arndt-Eistert, Curtius, Lossen, Schmidt, Hofmann, Beckmann, Neber, Stieglitz. Baeyer-Villiger reaction; Dakin reaction. Cascade reactions in organic synthesis Retrosynthesis and Functional Group Interconversion (FGI) (Prof. Stephen Connon) 9 lectures and 2 tutorials covering: Functional group interconversions Oxidation of alcohols Alkene oxidation Reduction of carbonyl compounds Other reduction reactions Retrosynthetic Analysis Definition and basic principles. Retrosynthetic analysis, synthons, disconnections, examples Recommended Reading List T. L. Gilchrist, Heterocyclic Chemistry, Prentice Hall, 1997 R. Brückner, Advanced Organic Chemistry: Reaction Mechanism, Academic Press. M. B. Smith, J. March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Wiley Interscience, 6th Ed., 2007. C. Elschenbroich, Organometallic, Wiley-VCH G. Spessard, G. L. Miessler, Organometallic Chemistry, Oxofrd University Press, 2009 R. W. Hoffmann, Elements of Synthesis Planning, Springer, 2009. E. J. Corey, X.-M. Cheng, The Logic of Chemical Synthesis, Wiley-Interscience. 1995. Module Pre N/A Requisite Module Co N/A Requisite Assessment Annual Examination Details* CH3303 Module Code* QUANTUM MECHANICAL CONCEPTS IN PHYSICAL CHEMISTRY Module Name* ECTS Weighting* Semester/term taught* Contact Hours* 5 Semester 1 33 Hours of Lectures Module Prof. Tony Morton-Blake, Prof Dónall MacDónaill, Prof. Rachel Evans Personnel Learning Outcomes Module Learning Aims Quantum Chemistry (Prof. Tony Morton-Blake) Module Content/ Description* 9 lectures and 2 tutorials covering: Brief review of quantum theory; wave functions, Schrödinger equations, Uncertainty Principle. Solution of the Schrödinger equation for a particle confined to a circle. Angular momentum. Schrödinger equation for chemical systems. Real and complex hydrogenic wave functions. Atomic orbitals. Variation Principle. The secular determinant and the interaction of states. Molecular orbitals. Bonding and antibonding molecular orbitals. Hückel molecular orbital theory; application to butadiene. pelectron charge and bond order. Incorporation of symmetries into Hückel theory; Application to benzene and larger aromatic hydrocarbons. Transition moment integral; electric dipole transitions. Spectroscopy (Prof. Rachel Evans) 8 lectures and 1 tutorial covering: Semiclassical treatment of light-matter interaction, Einstein’s coefficients and lasing Time-dependent perturbation theory (basics), Fermi’s golden rule Born-Oppenheimer approximation, Vibrational-rotational spectroscopy: Infrared spectroscopy, Selection rules for infrared spectroscopy, Rotational spectroscopy, Selection rules for rotational spectroscopy Fundamentals of electronic spectroscopy, Vibronic structures, Franck-Condon’s factors Orbital and spin rules and Fermi’s golden rule Group Theory (Prof. Dónall MacDonaill) 8 lectures and 1 tutorial covering: 1.2.1 Basics: Symmetry elements and operations. (1 lecture) Point Groups: symmetry classification of molecules. (1 lecture) Representations: introduction of numbers. (1 lecture) Reducing Representations (1 lecture) 1.2.2 Applications Simple applications in chemical bonding (2 lecture) Applications in molecular rotational and vibrational spectroscopy (1 lecture) Applications in Molecular Orbital calculations, projection operators - relates to the quantum chemistry course (2 lectures) Recommended Reading List Module Pre N/A Requisite Module Co Requisite Assessment Details* Annual Examination CH3304 Module Code* MOLECULAR THERMODYNAMICS AND KINETICS Module Name* ECTS Weighting* Semester/term taught* Contact Hours* 5 Semester 2 33 Hours Module Prof. Michael Lyons, Prof. Michael Bridge Personnel Learning Outcomes Module Learning Aims Module Content/ Description* Thermodynamics, quantum mechanics and statistical thermodynamics States, configurations, distributions Boltzmann distribution (1 Lecture) Molecular partition function (q) (2 Lectures) Thermodynamic functions in terms of q (1 Lecture) Determination of q for molecular translation, rotation, vibration and electronic states (1 Lecture) q, Q: molecular and canonical ensemble (1 Lecture) Explicit expressions for U, H, A, G, S, Cv etc (2 Lectures) Entropy and 3rd Law; residual entropy; Cv for solids; Cv for diatomic gases (2 Lectures) Equilibrium, Kc and q (1 Lecture) q and reaction rates – calculating rate constants and testing mechanisms (1 Lecture) Electrochemical Thermodynamics Electro ystems: fuel cell thermodynamic; Electrochemical potential; conditions for electrochemical equilibrium; potentiometric sensors (2 Lectures) Ionic Systems - Ion/solvent interactions; ion/ion interactions; conductivity in electrolyte solutions (2 Lectures) Interfacial Electrochemistry - Models of interface region ; Transport processes in electrochemistry; Electrode kinetics, Butler Volmer and Marcus-Hush approaches; Kinetics ofmultistep electron transfer processes; electrocatalysis (5 Lectures) Molecular collisions - Review of simple collision theory and its limitations. Potential energy curves and classical motion over a surface. Reaction cross sections and their link to rate constants (1 Lecture) The transition state – the derivations - The Eyring transition state theory: thermodynamic approach and the statistical mechanical approach (1 Lecture) Transition state theory – applications. Comparison with simple collision theory. Calculations of rate constants. Bimolecular rate constant from first principles. Temperature dependence of rate constants. Kinetic isotope effects. Entropies of activation (1 Lecture) Kinetics in the liquid phase - Comparison of liquid and gas phase reactions, radical scavenging, (1 Lecture) Diffusion controlled reactions - Stokes-Einstein relation, influence of solvent viscosity and temperature, electrostatic forces between ions. The theory of unimolecular reactions. (1 Lecture) Activation controlled reactions - Effect of electrostatic interactions, influence of solvent dielectric constant, entropy and volume of activation, influence of pressure, influence of ionic strength, kinetic salt effect. (1 Lecture) Experimental methods in gas and solution phases (1 Lecture) Modern Gas phase kinetics (1 Lecture) Recommended Reading List Module Pre N/A Requisite Module Co N/A Requisite Assessment Annual Examination Details* Module Code* CH3403 ANALYTICAL METHODS Module Name* ECTS Weighting* Semester/term taught* Contact Hours* 5 Semester 1 33 Hours of Lectures Prof. Wolfgang Schmitt, Prof. Paula Colavita, Prof. Michael Lyons, Prof. Thorri Module Gunnlaugsson Personnel Learning Outcomes Module Learning Aims Understanding and application of analytical techniques (may be applied in the JS Inorganic Chemistry laboratory course) To learn types, applications and theoretical background of spectroscopy techniques relevant to organic synthesis Module Content/ Analytical Methods in Inorganic Chemistry (Prof. Wolfgang Schmitt) Description* 9 lectures and 2 tutorials covering: Lecture 1 – Lecture 3: IR spectroscopy in Inorganic Chemistry: Theoretical concepts; Instrumentation; Characteristic group vibrations of common organic ligands; IR spectra of important coordination complexes; Tendencies of related complexes; IR spectra of amino acid-stabilised complexes, IR spectra of polynuclear complexes; IR spectra of bioinorganic model compounds; IR spectroscopy of carbonyl complexes and derivatives; Quantitative methods in IR spectroscopy; Raman spectroscopy: Theoretical concepts and examples of inorganic compounds; Lecture 3 – Lecture 7: NMR spectroscopy in Inorganic Chemistry; Theoretical concepts; Instrumentation; 1H-NMR spectra of representative complexes and tendencies; carbonyl complexes and related cluster compounds; phosphine complexes; 13C-NMR spectra of representative complexes and tendencies, 11B-NMR;195Pt-NMR; multinuclear NMR; NMR of paramagnetic systems; Fluxional NMR, Solid state NMR; Solid state NMR spectra of representative complexes and tendencies; EPR in Inorganic Chemistry; Theoretical concepts and EPR spectra of selected coordination complexes (depending on the time available); Lecture 8 – Lecture 9: Molecular Magnetism: Types of magnetism; Spin-spin coupling, Spinorbit coupling, Zeemann effect, case study: analysis of simple dinuclear copper(II), cobalt and nickel(II) complexes; Instrumentation; Analytical Methods in Physical Chemistry (Prof. Paula Colavita, Prof. Michael Lyons) 9 lectures and 2 tutorials covering: Statistics (4 Lectures) • Analytical Method development • Distributions, Samples and Estimators • Reporting values: errors, CI, Significant Figures • Two sample tests • Chi-square and fits • Figures of merit Analytical Spectroscopy (4 Lectures) • Fundamentals of spectroscopic instrumentation • Quantitative Determinations using Absorption/Emission • Analytical Atomic Spectroscopy: AAS, AES (XRF) Analytical Electrochemistry (3 lectures) • Capacitive vs. Faradaic currents • Limit of Detection • Voltammetry: sweep & pulse methods (CV, DPV, SV) • Analysis of heavy metals and organics • Electrochemical instrumentation (electronics, Op-Amp, etc.) Organic spectroscopy (Prof. Thorri Gunnlaugsson) 9 lectures and 2 tutorials covering: Mass spectrometry: EI-MS FAB ESI Maldi Tandem MS/MS Fragmentation pattern; McLafferty rearrangement Mass spectra by functional group Recommended Reading List Structural Methods in Inorganic Chemistry, 2nd Ed., E.A.V. Ebsworth, D.W.H Rankin, S. Cradock Blackwell Scientific Publications, 1991; Inorganic Spectroscopic Methods, A.K. Brisdon Oxford University Press, 1998; Inorganic Chemistry, D.F. Shriver, P.W. Atkins and C.H. Langford, 2nd Ed., Oxford University Press, 1990; Inorganic Chemistry C.E. Housecroft and A.G. Sharpe 2nd Ed, Prentice-Hall, 2005.. M. Hesse, H. Meier, B. Zeeh, Spectroscopic Methods in Organic Chemistry, Thieme, 2nd Edition, 2007 Module Pre N/A Requisite Module Co N/A Requisite Assessment Details* Annual Examination Module Code* CH3404 Module Name* ECTS Weighting* Semester/term taught* Contact Hours* BIOMATERIALS & MACROMOLECULES 5 Semester 2 33 Hours of Lectures Module Prof. Rachel Evans, Prof. Aidan McDonald, Prof. Thorri Gunnlaugsson, Prof. Eoin Scanlan Personnel Understand the role of metal and peptide for biological processes Understand metabolic processes of certain substrates Understand catalytic cycles for enzymes Learning • Outcomes • • Appreciate the importance and difficulties of model studies Introduction to bioinorganic chemistry and the natural roles metals play in biology. Module Learning The student is provided with a brief introduction to the coordination chemistry of Aims metals in biology, and to the spectroscopic techniques employed to study metals in biology. A variety of metalloenzymes and their Chemistry are discussed in detail. One experiment in the practical course is directly linked to metalloenzyme chemistry and thus the Bioinorganic section of this module. Learning outcomes: identify biological ligands; identify techniques to probe metals in biology; be able to predict catalytic cycles of metalloenzymes; have a deep understanding of Mn, Fe, Cu redox chemistry and be able to relate that to biological transformations. Soft Matter (Prof. Rachel Evans) Module Content/ 9 lectures and 2 tutorials covering: Description* Surface and interfacial tension (1 lecture) Langmuir adsorption isotherm, insoluble monolayers, physical states (1 lecture) Surfactants: properties, structure, thermodynamics of micelle formation, aggregation number, structure (1 lecture) Lyotropic liquid crystal phases, biological membranes (1 lecture) Colloidal dispersions – stability, preparation, Hamaker theory, DVLO theory, applications (3 lectures) Polymers: morphology-property relationships, solvation thermodynamics, molecular weight determination, viscoelasticity, glass transition temperature Bioinorganic Chemistry (Prof. Aidan McDonald) 9 Lectures and 2 Tutorials The course will provide students with an introduction to the natural roles metals play in Biology. The course will consist of 9 lectures, and 2 tutorials. The topics to be covered during the course are listed below: Lecture 1: Introduction to Bioinorganic Chemistry Lecture 2: Spectroscopic Techniques in Bioinoragnic Chemistry Lecture 3: Photosynthesis - Photosystem II - manganese, iron, magnesium Lecture 4: Dioxygen Transport - iron and copper Lecture 5: Dioxygen Activation - iron and copper Lecture 6: Electron Transfer - iron/sulfur clusters, blue copper Lecture 7: Nitrogen Fixation - nitrogenase Lecture 8: Hydrogenases - iron, nickel Lecture 9: Metals and Reactive Oxygen Species - Neurodegeneration Bioorganic Chemistry (Prof. Thorri Gunnlaugsson, Prof. Eoin Scanlan) 9 Lectures and 2 Tutorials DNA: Basic structure and components, single- and double stranded DNA, A-, Band Z-forms; cell cycles, natural DNA synthesis; chemical DNA synthesis; polymerase chain reaction; automated synthesis. Amino acids and peptides: Basic structure and properties; protein structure, chemical peptide synthesis and coupling agents (DCC, DIC, EDCI, HATU), protecting groups; Merrifield synthesis; automated processes, in vivo protein biosynthesis. Carbohydrates: Recap SF chemistry, configuration of natural sugars, glycosyl donors and acceptors, coupling methods and protecting group chemistry. Glycoconjugate synthesis. Porphyrins: nomenclature, biological examples, heme, chlorophyll; applications in PDT, NLO. Recommended Reading List G. Barnes and I. Gentle, Interfacial Science: An Introduction, Oxford University Press, 2nd Edition - Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life - An Introduction and Guide [Paperback], Wolfgang Kaim, Brigitte Schwederski, WileyBlackwell - The Biological Chemistry of the Elements: The Inorganic Chemistry of Life [Paperback] - Bioinorganic Chemistry; Bertini, Gray, Lippard, Valentine; University Science Books - Principles of Bioinorganic Chemistry; Lippard, Berg; University Science Books J. J. R. Frausto da Silva, R. J. P. Williams, OUP Oxford Module Pre N/A Requisite Module Co N/A Requisite Assessment Details* Annual Examination CH3080 Module Code* PRACTICAL CHEMISTRY Module Name* ECTS Weighting* 15 Semester 1 Semester/term Semester 2 taught* Contact Hours* 33 Hours of Lectures Module Personnel Learning Outcomes Module Learning Aims Module Content/ Description* Recommended Reading List Module Pre Requisite Module Co Requisite Practical in-course assessment through laboratory reports Assessment Details* CH3441 Module Code* MEDICINAL CHEMISTRY Module Name* ECTS Weighting* 5 Semester 1 Semester/term Semester 2 taught* Contact Hours* 33 Hours of Lectures Module Personnel Learning Outcomes Module Learning Aims This module covers material dealing with fundamental medicinal chemistry. It encompasses Module Content/ CH3041, CH3042 and CH3043 Description* CH3041 - Introduction to Medicinal Chemistry - 15 Lectures - M. Southern Principles of drug action; drug properties; drug targets and modes of action. Molecular components of cells: lipids, proteins, nucleic acids. Control through non-covalent interactions: electrostatic, hydrogen bonding, hydrophobic. Conformations of biological macromolecules, organisation of cell, basic biochemical machinery. Sites for drug action: DNA/RNA (alkylation, intercalation etc.), enzymes (inhibition), receptors (agonism, antagonism).Enzyme substrates/transition states, receptor ligands (hormones and neurotransmitters) as lead compounds for drug development. Drug development, e.g. from a biologically active natural product: identification of pharmacophore, application of QSAR. Alternative sources of lead compounds (random screening, combinatorial chemistry, protein crystallography/molecular modelling).Pharmacodynamics: drug transport, stability, metabolism. Use of pro-drugs. CH3042 - Antiviral and Anticancer Chemistry - 9 Lectures - E. M. Scanlan Antimetabolites-antifolates, pyrimidine and pruine antagonists; Alkylating agents; Microtubule active agents. CH3043 - QSAR Methods - 9 Lectures - I. Rozas Hansch Model Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Details* Annual Examination CH3446 Module Code* MICROBIOLOGY & PHARMACOLOGY Module Name* Medicinal Chemistry II - Microbiology and Medicinal Chemistry ECTS Weighting* 5 Semester/term Semester 2 taught* Contact Hours* 33 Hours of Lectures Module Personnel Learning Outcomes Module Learning Aims This module covers antimicrobial agents, antiinfective agents, antimalarial chemistry and Module Content/ aspects of industrial chemistry. Description* Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Details* Annual Examination and partial assessment by essay CH3447 Module Code* BIOCHEMISTRY & PHARMACEUTICAL CHEMISTRY Module Name* Medicinal Chemistry III ECTS Weighting* 5 Semester/term Semester 2 taught* Contact Hours* 33 Hours of Lectures Module Personnel Learning Outcomes Module Learning Aims Module Content/ Description* Protein Structure, Function, Activity and Regulation (15L) Receptors, Drugs and the Autonomic Nervous System (9L) Steroids (9L) Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* CH3601 Module Code* COMPUTATIONAL CHEMISTRY Module Name* ECTS Weighting* 5 Semester/term Semester 2 taught* Contact Hours* 30 Hours of Lectures Module Personnel Learning Outcomes Module Learning Aims Module Content/ Description* This module covers a range of topics on offer from computational numerical optimization methods, molecular quantum chemistry and an introduction to static and dynamic atomistic simulation. It encompasses: CH3062 CH3063 CH3067 Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* CH3602 Module Code* COMPUTATIONAL CHEMISTRY II Module Name* ECTS Weighting* 5 Semester 1 Semester/term Semester 2 taught* Contact Hours* 54 Hours of Lectures Module Personnel Learning Outcomes Module Learning Aims Module Content/ Description* This module covers programming and related skills, with course on Unix, Fortran 77 and Fortran 90(+). This material is assessed during the year through practicals and assignments. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment In-course assessment Details* Module Code* Module Name* ECTS Weighting* CH4102 ADVANCED ORGANIC CHEMISTRY I 5 Semester/term Semester 2 taught* Contact Hours* Module Personnel Learning 11 Hours of Lectures; 1 Hour of Tutorials Outcomes Module Learning Aims These modules involves core lectures in comptemporary organic synthetic methods Module Content/ and heterocyclics and drugs. Description* CH4001 Principles and historical development of synthetic methods. Fischer, Perkin, Woodward, Corey and modern approaches towards synthesis. Retrosynthetic analysis: disconnections, synthons, retrons, latent polarities. Linear versus convergent syntheses. Protecting group strategies. Chemo-, regio-, stereo- and enantioselective methods. Synthesis of heterocycles. Examples from the literature: e.g. terpinol, cage compounds, steroids, longifolen, vitamins, drugs, artesiminin, brevetoxin or others CH4033 Detailed chemistry of selected classes of heterocyclic drugs, including the quinolone antibiotics, histamine H2 antagonists, etc. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual examination Details* Module Code* Module Name* ECTS Weighting* CH4103 ADVANCED ORGANIC CHEMISTRY II 5 Semester/term Semester 2 taught* Contact Hours* 9 Hours of Lectures; 2 Hours of Tutorials Module Personnel Learning Outcomes Module Learning Aims The following topics will be covered in this lecture course: Module Content/ Description* Radical Chemistry: Generations of radicals, physical properties of radicals, their stability and structure, simple radical reactions on hydrocarbons, the radical chain reactions, persistent radicals, ways of generating radicals using photolysis, thermolysis and redox reactions, exploring the mechanism for various named radical reactions which will be followed by in-depth discussion of large numbers of reactions which will involve: coupling, addition, substitution, reduction, fragmentation and rearrangement reactions. Protection Chemistry: Introduction to the concept of protection chemistry most of the lectures will focus on the strategy and the methods used for the protection and deprotection of amines and carbocyclic acid s, alcohols (and diols) and carbonyl functional groups. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4104 ADVANCED INORGANIC CHEMISTRY I 5 Semester/term Semester 2 taught* Contact Hours* 9 Hours of Lectures; 2 Hours of Tutorials Module Personnel Learning Outcomes Module Learning Aims CH4005 - Advanced Organometallic Chemistry Module Content/ Main synthetic approaches in modern Organometallic Chemistry. Types and properties of MDescription* C bonds. Main reactions and mechanisms. New ligands in Organometallic Chemistry. Role of the metal nature. Stabilisation of unusual oxidation states. Organometallic Chemistry of water. Bio-Organometallic Chemistry. Supramolecular Organometallic Chemistry. CH4014 - Main Group Organometallics This course deals with the organometallic chemistry of Groups 1, 2, 13, 14 and 15. The relationship between structure and reactivity is explored, with particular reference to alkyl lithiums, grignards, dialkyl zinc and trialky aluminium compounds (6-7 Lectures). Finally selected aspects of contemporary main group chemistry are explored (1-2 lectures). Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4105 ADVANCED INORGANIC II 5 Semester/term Semester 2 taught* Contact Hours* 18 Hours of Lectures; 5 Hours of Tutorials Module Personnel Learning Outcomes Module Learning Aims CH4004 – Heavy Transition Metals Module Content/ Description* Lecture 1: The course begins with a revision of concepts reapplying them to the Heavy Metals e.g. definitions of transition metal and lanthanide and actinide, nature of d and forbitals, radial distribution functions and lanthanide contraction Lecture 2: Gives an overview of the electronic spectra of the 2nd and 3rd row transition metal and f-block metal elements Lecture 3: Details the common geometries and coordination numbers of compounds and complexes, particularly focussing on coordination number 7 and 8, variations in the stability of oxidation states Lecture 4: Looks at the Magnetic Properties of TM and f-block metals, Russell Saunders coupling and the spin-only formula Lecture 5: The prevalence of M-M bonding in the heavier TM series and detailed examples from the oxide and halide chemistry of Mo, W, Nb and Ta. Lecture 6: Re chemistry: the fluorides, chlorides and oxo compounds. Uses simple MO theory and electron counting to examine the formation of M-M bonds Lecture 7: Ru and Os oxo compounds giving consideration to MO interactions General Properties of the Lanthanides: History, extractions, separation and general chemistry Lecture 8: uses of the Lanthanides, luminescent applications, catalysis, MRI, NMR shift reagents, organometallic compounds of the lanthanides Lecture 9: brief overview of the chemistry and organometallic chemistry of the actinides CH4011 - Advanced Coordination Chemistry Spin-crossover (SCO) phenomena and how to generate this condition, functional aspects of SCO, potential use of SCO, supramolecular chemistry, metallo-supramolecular chemistry, coordination chemistry, metallo-helicate chemistry design and synthesis, catenane and rotaxane design and synthesis, kinetic vs. thermodynamic templates, self-assembly, Hbonding, p-p interactions, charge-transfer, metal-templation, metallo-polyhedra syntheis and design, experimental aspects of synthesis and characterisation, Metal-organic frameworks and coordination polymers, design strategies and synthesis, potential uses. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4106 ADVANCED PHYSICAL CHEMISTRY I 5 Semester/term Semester 2 taught* Contact Hours* 14 Hours of Lectures; 3 Hours of Tutorials Module Personnel Learning Outcomes Module Learning Aims CH4006 - Photochemistry Module Content/ Description* Introduction and Singlet states: Types of photochemical reactions. Photon energy. Fluorescence – relationship of quantum yields to radiative and measured lifetimes. Radiationless processes. Jablonski diagram. Triplet states: nature, population, spin-orbit coupling, phosphorescence, energy transfer, reactions Transient Spectroscopy: Fluorescence lifetime determination: laser flash photolysis, femtosecond/picosecond methods, Transient IR and Raman. Photoreduction of benzophenone and derivatives as an illustrative example of an organic molecule in solution Another illustrative example of photo-reactions, e.g. Photo-induced electron transfer reactions, photochemistry of co-ordination compounds, photochemistry of nucleic acids. Solar energy conversion. Primary processes of photosynthesis and Gratzel CH4008 – Advanced Physical Chemistry Chemically modified electrodes. Preparation , characterization and properties of redox active and inactive self assembled monolayer films on electrode surfaces. Preparation and characterization of self assembled monolayer (SAM) thin films. Electrochemical and catalytic behaviour of SAM film modified electrodes.Classification, synthesis and fundamental properties of electroactive polymer materials. Ionic and electronic conductivity mechanisms exhibited by electroactive polymers. The experimental determination of electronic and ionic conductivity in electroactive polymers using microelectrode and complex impedance spectroscopic methods. The use of electroactive polymer materials as amperometric chemical sensor devices. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4107 ADVANCED PHYSICAL CHEMISTRY II 5 Semester/term Semester 2 taught* Contact Hours* 16 Hours of Lectures; 6 Hours of Tutorials Module Personnel Learning Outcomes Module Learning Aims CH4007 – Quantum Chemistry Module Content/ Description* Time-dependent theory: inversion in the NH3 molecule, Fermi Golden Rule. Quantum chemical description of polymers: Bloch functions, Brillouin zone, energy bands. Rotation of homonuclear diatomic (and some other) molecules, bosons and fermions, ortho and para H 2, their interconversion and spectra. CH4009 – Solid State Point Defects: An introduction to the nomenclature and occurrence of point defects in a variety of solids. A first principles derivation of the nember of intrinsic defects in ionic crystals as given by ststistical thermodynamics. Grossly defective materials: the nature and occurrence of non-stoichiometry in solids, its control and effects on the properties and the modes of stabilisation of grossly defective crystals. Dislocations: the nature and occurrence of dislocations, the energetics of dislocation formation and the effects of dislocations on the strength of materials and on the rates of crystal growth and stabilisation. Surfaces: the nature of grain boundaries and the energetics of surface formation and stabilisation, the aggregation of defects. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4108 OPTION MODULE 5 Semester/term Semester 2 taught* Contact Hours* Module Personnel Learning Outcomes Module Learning Aims In this module students select four advanced option courses: Module Content/ Description* CH4003 - Aspects of Inorganic Chemistry Bio-inorganic chemistry, metallo-enzymes, alkalides and electrides: definitions, synthesis, structures and properties. Polyhedral silsesquioxanes and metallasilsesquioxanes and their applications. CH4021 - Molecular Dynamics An introduction to the simple yet powerful method for solving the many particle equations of motion for molecular systems; applications in chemistry. CH4022 - Matter Transport in Solids Ionic conductance and diffusion processes in solids considered from first principles; applications include solid state reactions, including corrosion of metals and alloys, and fast ion conductors and their uses in advanced battery systems and chemical sensors. CH4023 - Quantum Chemistry Quantum operators; perturbation theory and applications (Stark effect); beyond the HartreeFock limit; vibrations in solids (phonons). CH4024 - Heterogeneous catalysis The course will examine the basic principles of catalyst and catalyst design including measures of catalyst activity. Examples of real world catalysts will be given including the use of zeolites for acid catalysed reactions within the petroleum industry and the design and performance of car exhaust catalysts and hydro-desulfurisation catalysts and there link to environmental legislation. CH4025 - Supramolecular Chemistry Host-guest chemistry and molecular recognition including relevance to biological processes and 'molecular engineering'. Self-assembly and anion sensing. CH4027 - Topics in Structural Chemistry A brief review of the preparation, structural chemistry and physico-chemical properties of (i) Molecular Crystals and (ii) Copper oxide superconductors emphasising the interplay between composition, structure and properties. CH4030 - Statistical Thermodynamics Application of statistical mechanics to study molecular motion in various states of matter; Fermi-Dirac and Bose-Einstein statistics. CH4031 - Organic Synthetic Methods II The modern Aldol Reaction in the stereoselective synthesis of molecules of medicinal/biological importance, particularly natural products that derive from the polyketide synthetic pathway. CH4034 - DNA Structure and Drug DNA complexes Spectroscopic tools for studying nucleic acids; structure of DNA (A, B and Z); covalent and non-covalent binding to DNA; relevance to drug design. CH4036 - Bio-Organic Chemistry Introduction; Catalytic antibodies; Combi-chem lite; Directed evolution; RNA world; Proteomics CH4037 - Electrochemical Biosensors The physical principles underlying electrochemical sensors. A survey of surface immobilized redox enzyme based biosensor devices using electrochemical transduction. Strategies for enzyme wiring. Self assembled monolayer based biosensors. CH4041 - Material Synthesis using Chemical Vapour Deposition The aim of this course will be to provide students with an introduction to the increasingly important technique of chemical vapour deposition (CVD). This method has extensive applications in both industrial processes and academic research, and is used to deposit thin films of various substances. Also, CVD has led to the synthesis of novel materials such as nanowires and nanotubes. The course will cover the basic principles of CVD, its use as the impetus for surface and gas phase reactions, and the various technological considerations relevant to the development of the technique. CH4042 - Fundamentals of Electrochemical Energy Conversion and Storage The course will deal with the physical electrochemistry which underpins electrocatalysis, fuel cells, batteries and super-capacitors. CH4080 - Molecular Informatics Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* CH4401 Module Name* ECTS Weighting* Advanced Medicinal Chemistry I 5 Semester/term Semester 2 taught* Contact Hours* 16 hours of lectures, plus tutorials Module Personnel Learning Outcomes Module Learning Aims CH4050 - Central Nervous System Module Content/ Description* * Cellular foundations of neuropharmacology: Cytology of the nerve cell, Bioelectric properties of the nerve cell, The steps of synaptic transmission, Aspects of the metabolism in the central nervous system * Neurotransmitter Postsynaptic Receptors: Classification & Definition * Modulation of synaptic transmission: Definitions, Second messengers * Neurotransmitters and their receptors: Aminoacids Glutamic acid –Glutamate: Synthesis & Metabolism, Glutamate receptors, NMDA receptor Glycine:Glycine receptors GABA: Distribution & Metabolism, GABA receptors: GABAA, GABAB & GABAC, Drugs acting on GABA receptors: Benzodiazepines, Barbiturates & Spasmolytics. *Neurotransmitters and their receptors: Acetylcholine (Synthesis -Choline acetyltransferase& Storage, Choline transportm Metabolism & Inactivation (Acetylcholinesterase), The cholinergic synapse, Cholinergic receptors -Nicotinic Receptors & Muscarinic Receptors, ACh drugs, ACh in disease states: Parkinson’s and Alzheimer’s diseases * Neurotransmitters and their receptors: Serotonin (Synthesis & Metabolism, Serotonin Transporter: A Representative Reuptake Pump, Location and Structure of the Serotonin Transporter, Mechanism of Action of the Serotonin Transporter, Transporter Inhibition: Selective Serotonin Reuptake Inhibitors, Serotonin receptors, Serotonin and Depression *Neurotransmitters and their receptors: Noradrenaline and Adrenaline (Generalities: Catecholamines, Synthesis and Metabolism of Catecholamines, Adrenergic neurons, Metabolic actions of Catecholamines, Noradrenaline transporter: Desipramine, Adrenoceptors -Classification beta-Adrenoceptors: Subtypes, Location and Function, Agonists and Antagonists, Transduction Mechanisms, Clinical Uses, beta-blocking drugs Alpha1-Adrenoceptors: Subtypes, Location and Function, Agonists and Antagonists Transduction Mechanisms, Clinical Uses, alpha1-blocking drugs: Benign Prostatic Hyperplasia alpha2-Adrenoceptors: Subtypes, Location and Function, Agonists and Antagonists Transduction Mechanisms, Clinical Uses, alpha2- drugs: Analgesics and Antidepressives Imidazoline Binding Sites * Neurotransmitters and their receptors: Dopamine (Synthesis and Metabolism, Dopaminergic neuron, Dopamine transporter & inhibitors, Dopamine receptors, Dopamine and Parkinson’s disease, Dopamine and schizophrenia * Neurotransmitters and their receptors: Neuroactive peptides (Generalities & differences with small neurotransmitters, Coexistence with Neurotransmitters, Classification, Opioid peptides and their receptors: agonists and antagonists, Vasopresin and Oxytocin and their receptors, Tachykinins: Substance P and Neurokinins, Cholecystokinin Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4402 ADVANCED MEDICINAL CHEMISTRY II 5 Semester/term Semester 2 taught* Contact Hours* 22 hours Module I. Rozas and External from DCU Personnel Learning Outcomes On successful completion of this module students should be able to: Module Learning Aims CH4052: • Explain computational methods that will help in the design of new drugs • Compare the different computational methods used in drug design and choose and explain which is the appropriate method for a given problem • Assess the problems associated with computational drug design. CH4056: • Explain the separation processes involved in different analytical methods • Select the most appropriate analytical method for the separation of potential drugs. CH4052 - Computational Medicinal Chemistry Module Content/ CH4056 - Analytical Methods Description* Computational tools in medicinal chemistry: data bases (Small molecules-cambridge vs. Big molecules-brookhaven), mechanoquantic methods (Semiempirical -application/examples, Ab initio and DFT- application/examples); computational methods based on clasic mechanics (Molecular mechanics -application/examples, Molecular dynamics -applications/examples) -examples done by students Different approaches to drug design: *selection of the biological target (receptor), selection and/or optimization of a leader compound (ligand) *receptor structure is known: 3d structure known (docking), 1ry structure known (protein homology) *receptor structure is unknown: Pharmacophore determination superimposing structures (fitting), "de novo" design , 2d-qsar: linear correlations: different parameters, 3d-qsar. Additional problems in drug design: *different conformations: conformational analysis methods: Systematic search, Random search -> Montecarlo High temperature molecular dynamics, Annealing *the environment: solvation models: Continuous, Discrete (solvent & membrane), Mixed (QM/MM) Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4403 Advanced Medicinal Chemistry III 5 Semester/term Semester 2 taught* Contact Hours* 16 Lectures; 2 Tutorials Module Personnel Learning Outcomes Module Learning Aims CH4053 - Site Specific Drug Delivery Systems Module Content/ CH4055 - Combinational Chemistry and Screening Methods Description* CH4053 Introduction – why a good in vitro profile is no indication of in vivo activity Description and appreciation of Ehrlich’s “magic bullet” insight The general methods of delivery are described (oral, implant, topical, i.v. etc) and the merits of each approach considered. After illustrating that oral delivery is the preferred method of delivery a drug’s journey is then considered in more detail. The numerous issues effecting a drug, or other chemical’s journey from bottle to site of action are discussed, including the acidity of the stomach, the phsysiochemical properties required, for example, sufficient solubility in both aqueous and lipid (cell membrane) based media (log P and log D). The drug must be water soluble enough for transport via the bloodstream but lipophilic enough to diffuse through the cell wall lipid bilayer. Other issues such as pKa, dissolution rate and site of absorption are discussed culminating in Lipinski’s rule of 5. Alternative methods of cell entry (aqueous pore, active transports, endocytosis) Brief discussion of P450 system in terms of metabolism and the effects of other agents in combination (ADME(T)/DMPK) Overcoming problems using prodrugs More specific look at options if a poor in vivo profile is observed and how to overcome the variety of problems e.g. low lipophilicity – prodrugs (defined) offer the simplest solution. Examination of the pitfalls, and the factors that can be influenced (solubility, tissue penetration, presystemic metabolism, site specificity, rate of onset/duration of action, toxicity (positive and negative), poor patient compliance, formulation problems). Different classes of prodrugs (bi/tripartite and mutual (carrier linked) and bioprecurors. Carrier linked Esters of acids or alcohols and associated electronic and steric effects on release in vivo. Sulfonates, phosphonates and amides described. Numerous examples of bi/tripartite and mutual ester and amide prodrugs affecting the various different factors of influence are provided. Examples applicable to topical absorption are also included Methenamine described. Bioprecursors The story of the development of the discovery of prontisil and bioprecursor prodrugs by Domagk. Definition and numerous examples of oxidative and reductive activation, including mechanisms of activation. In depth analysis of the mode of action of acyclovir and how it exploits virus encoded kinases to ensure selective activation solely in infected cells. Macromolecular prodrugs In which the drug is attached to a polymer. Physiochemical properties dominated by that of the polymer. Uptake in the GI tract is poor and intravascular delivery is generally required, size issues - capillaries (especially in the lungs) can become clogged). Loading is variable. Diffusion across membranes is poor but endocytosis mechanisms can be effective. Coverage of issues such as biodegradability, addition of solubilising side-chains and linkers to aid release. Examples of natural hormones, contraceptives, methotraxate and doxorubicin (PK1) on polymers. The blood brain barrier Examination of the extra issues involved for drugs to cross the blood-brain-barrier and how dihydropyridine prodrugs can achieve this. Description of the mode of action of nerve agents (via deactivation of acetylcholinesterase) and the associated effects. Mode of action of antidotes for the peripheral nevous system and prodrug antidotes for the CNS. A penicillin based prodrug to cross the BBB to treat bacterial meningitis. Discussion of LDopa’s ability to cross the BBB, mode of activation, mode of action and problems with peripheral activation (preventing the active agent, dopamine, entering the brain). Use of carbidopa and benzerazide (dopa decarboxylase inhibitors that don’t cross the BBB) to allow low dosing and effective use of L-Dopa. Use of a MAOI prodrug activated by dopa decarboxylase (in combination carbidopa to prevent peripheral activation) that is released within the brain, preventing the incompatibilities of MAOIs within the periphery. Liposomes as delivery devices General theories, loading strategies, types of vesicles, phospholipids used, targeting issues (concentration in the liver), transport in macrophages, stealth liposomes, targeted liposomes. Case Studies Case study – Prodrugs of Taxol, study of the attempts to improve the bioavailability of Taxol by increasing its water solubility. New Targets/Technologies Case Study – Glivec a CML treatment. A brief discussion of the genetic events leading to the formation of the Philidelphia Chromosome (and other mutants) responsible for the expression of rogue kinases. Development of Glivec from a PKC inhibitor with activity against BCR-ACL. Brief mention of Irresa and Tarceva, targeting EGFR, and active against prostate, pancreatic, colorectal renal-cell and oesophageal Case Study – Herceptin, a treatment for breast cancers in which HER2 is overexpressed. Overview of human epithelial growth factor receptor 2 and the requirements for activity of herceptin. Definitions and background (including chemical uses as catalysts) of monoclonal antibodies including interaction and the use of HER2 as the antigen. Description of the production and isolation of antibodies and the subsequent humanisation by gene conversion mutagenesis, modelling and nucleic acid exchange to humanise the coding for the recognition region. mAbs alone can induce an immune response, block highly expressed and activated receptors for growth factors or inhibit angiogenesis. They can also be used for targeting radionucleides, cytotoxic drugs and toxins. Best example of FDA approved treatment is Mylotarg (gemtuzumab) a humanised CD33 mAb linked to calicheamicin. Finally mention of Antibody directed enzyme prodrug therapy CH4055 Historical overview; biological combinatorial techniques; combinatorial strategiy. Drug development process; time frames, costs, approach and strategies; lead discovery and optimisation. Medicinal chemistry and drug development. Solid phase techniques, split and mix techniques, instrumentation. Immobilized reagents; solid phase natural product synthesis. Resins; supports; crosslinking agents; spacers. Synthetic examples; Ugi reactions. Screening Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4404 ADVANCED MEDICINAL CHEMISTRY IV 5 Semester/term Semester 2 taught* 12 Lectures; 2 Tutorials Contact Hours* Module Personnel Learning Outcomes Module Learning Aims CH4051 - Medicinal Chemistry Cardiovascular System Module Content/ CH4054 - Case Studies Description* CH4051 Introduction Brief description of the types of disease and number of deaths associated with the cardiovascular system. Focus on hypertension, definition and associated problems, e.g. increased risk of stroke. Treatments for hypertension Beta blockers - Beta adrenergic antagonists An overview – The nervous system and how the adrenergic (sympathetic) system fits into it. The basic neurobiology of the somatic, sympathetic and parasympathetic systems Biosynthesis and metabolism of adrenaline and noradrenaline A detailed examination of adrenoreceptors – subtypes, structure, biochemical cascades initiated and the associated physiological outcomes of activation of the different subtypes. Important interactions of adrenaline with adrenoreceptors followed by the a/b selectivity discovered by Ahlquist - larger alkyl groups on the amine enhance activity at the b receptors – hydrophilic pocket hypothesis. The effect of adrenaline in differtent organs with different levels of expression of different subtypes. An overview of the biological effects of different subtype selective ant/agonists. Focus on b-adrenoreceptor antagoniosts (b-blockers) and Black’s attempts to alleviate angina leading to the development (via dichloroisoprenaline) of pronethalol – active against angina with an additional antihypertensive effect. The first b-blocker used clinically. The (serendipitous) discovery of propanolol (now the benchmark for activity), racemic synthesis included. An overview of the positive and negative physiological effects. Examples of other 1st generation b-blockers including SAR 2nd generation - Discovery of cardioselective (b1 (heart) activity > b2 (lung)) b-blocker practolol - alleviating problems for asthmatics. Mention of the controversy around the different activities of the o/m/p aromatic substitution patterns. Further side-effects (was withdrawn) and other clinically employed 2nd generation b-blockers. 3rd generation b-blockers – extention from the amine, examples (focus on xalmoterol) and SAR. Finally diverse uses of b-blockers. b-blockers have a similar ether/hydroxy/amino backbone with varying R groups, syntheses are similar but there issues with their chiral preparation which is discussed. Angiotensin converting enzyme (ACE) inhibitors Overview of the history and current knowledge of the Renin-Angiotensin System (RAS) and assessment (not very promising to start with) of different targets within it. Story of the development of the first ACE inhibitors from early (unsuitable) snake venom peptides. Structural knowledge of ACE was limited - carboxypeptidase A (another zinc protease) was employed as an analogous enzyme that cleave a single terminal aminoacid raher than the two that ACE cleaves. Analysis of the CPA active site and the elaboration of CPA inhibitor benzylsuccinic acid and its elaboration to Captopril. Two syntheses of captopril, racemic with resolution and asymmetric. Side effects of Captopril and the extention of the byproduct inhibitor strategy resulting in the formation of Enaprilat. Enaprilat is not absorbed too well making oral delivery difficult, simple esterification (enapril) solves this – tie in with drug delivery. Synthesis of enapril(at), lisinopril and quinapril(at). Consideration of the bioactive conformation and synthesis of cilazapril and two syntheses of ramipril. Synthesis of fosinopril More recent information on ACE, N-domain, C-domain, new inhibitors, crystal structure data, binding, modelling. Discussion of the mode of activity, not as simple as initially thought. Another target in the RAS – Angiotensin II antagonists, development of losartan, including two syntheses. Comparison of structures and intereactions with the AII receptor. Synthesis of valsartan Calcium Channel antagonists/blockers Brief overview of calcium channels. And how the different classes of drugs have different physiological outcomes are employed to treat different cardiovascular problems. A racemic and chiral synthesis of verapamil. Synthesis of the dihydropyridines nifedipine, K8644 and amlodipine and diliazam. Diuretics Overview of diuretics from the early mercury based compounds in the 1920s. The sites of action of different diuretic drugs. Structures, uses and mode of action of: carbonic anhydrase inhibitors such as acetazolamide; loop diuretics such as bumetanide and furosemide; the thiazides such as chlorothiazide, hydrochlorothiazide, chlorthalidone and indapamide; potassium sparing diuretics such as triamterine and amiloride. An aldosterone antagonist spironolactone. Miscellaneous Very brief mention of organic nitrates isosorbide dinitrate, nitroglycerin and amylnitrate. Very brief mention of the cardiac glycosides such as digitoxin. Brief discussion of the “polypill” containing low doses of 3 antihypertensive drugs, folic acid, aspirin and a statin at low doses. CH4054 Asthma Description of the disease, etiology and number of deaths associated with asthma. Analysis of the potential targets for treatment, histamine, leukotrienes and their associated problems. Adrenaline is known to dilate the airways – potential treatment? Very quick reminder of the adrenergic nervous system (covered in more detail in the CVS course) focusing on b2-agonists Examination of adrenaline which can be employed in a clinical setting is not an ideal drug dramatic side effects and poor pharmacokinetics. The work of Lands leading to the development salbutamol – Understanding the structural alterations made to reduce metabolism by COMT but retain activity at the b2 adrenoreceptors. Increasing the duration of action - salmeterol Overview of other approaches and treatments available Gastric and duodenal Ulcers Description of the disease and hi-lighting the problems associated with ulcers prior to the development of effective anti ulcer treatments. Etiology of the disease and description of the risks SKF took pursuing histamine as a target other mediators and no proof of histamine subtypes mediating acid secretion at the time. SAR studies based on the different effects of model compounds on uterus and heart tissue. Development of histamine from an endogenous agonist to the effective antagonist cimetidine - the usual methods of developing antagonist behaviour from agonists proved unsuccessful, sales figures included. Synthesis of cimetidine Further work at Glaxo resulting in the development of ranitidine (no P450 issues) including its synthesis and some sales figures. SAR studies Other drugs jumping on the bandwagon - tiotidine, famotidine (including synthesis). Glaxo’s attempts to prolong activity Proton pump inhibitors – omeprazole The role of H. Plyori in ulcers and the introduction of triple therapies. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4405 ADVANCED MEDICINAL CHEMISTRY V 5 Semester/term Semester 2 taught* Contact Hours* Module Personnel Learning Outcomes Module Learning 20 Lectures; 4 Tutorials Aims CH4025 - Supramolecular Chemistry Module Content/ CH4031 - Organic Synthetic Methods II Description* CH4034 - DNA Structure and Drug DNA complexes CH4036 - Bio-Organic Chemistry CH4025 The following topics will be covered in this lecture course (but many more will also be featured): Non-covalent interactions: electron-pair donor-acceptor, electrostatic, hydrogenbonding, p-donor-p-acceptor, van der Waals. Importance of geometric control: preorganisation. Role of solvent: hydrophobic interactions. Cation binding: crown ethers, cryptands, acyclic receptors. Applications in sensors and phase-transfer catalysis. Anion recognition: cationic, metal-based and neutral receptors. Recognition of neutral molecules by hydrogen-bonding and/or p-p interactions in organic solvents, and by hydrophobic interactions in water. Cyclodextrins, cyclophanes. Supramolecular catalysis, self-assembly of supramolecular aggregates, coordination networks and crystal engineering. Molecular motors and machines. Complexed structures formed by self-assembly and the basic concepts of nanochemistry. CH4031 Introduction Overview of the history of chemotherapy as a weapon against cancer. The Taxol story - screening isolation and so on Microtubule active agaents - Biochemical background, mode of action Taxol Different disconnective approaches to Taxol Holton’s synthesis of Taxol, disconnection, key points and the chemo-, regio-, stereoselectivity (as appropriate) of each step. Nicloaou’s synthesis of Taxol, disconnection, key points and the chemo-, regio-, stereoselectivity (as appropriate) of each step.Taxol SAR Epothilone Epothilone history and background information Nicloaou’s synthesis of Epothilone, disconnection, key points and the chemo-, regio-, stereoselectivity (as appropriate) of each step. CH4034 Introduction. Survey of properties of nucleic acids. Primary structure of DNA and RNA. Spectroscopy. Ultraviolet, circular dichroism, infra-red and NMR spectroscopies. Evidence for double-strand formation, base stacking, sugar pucker and nucleotide conformation, Watson-Crick base-pairing. Structures of A-DNA, B-DNA, Z-DNA. X-ray methods; fibres and oligonucleotides. Main features such as pitch, tilt, major and minor groove nucleotide conformation etc. Binding to DNA. Groove binders (e.g. netropsin), triplex-forming oligonucleotides. Intercalators. Application of Uv/vis, fluorescence, NMR, X-Ray, viscosity and electrophoretic methods (Cisplatin has also been considered in previous years Quadruplex DNA Guanine tetrads, Hoogsten binding. Drug binding. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* Module Code* Module Name* ECTS Weighting* CH4601 MATERIALS CHEMISTRY 1 5 Semester/term Semester 2 taught* Contact Hours* 6 Hours Module Personnel Learning Outcomes Module Learning Aims CH4022 - Matter Transport in Solids Module Content/ CH4063 - Simulation Techniques in Solids Description* CH4022 Mobility of defects in ionic solids - experimental determination of energies and entropies for defect formation, migration and interaction. Nature of diffusion in solids and some related phenomena - the diffusion coefficient, D, correlation factors - the Nernst-Einstein equation - techniques for measurement of values of the diffusion coefficients in solids. Solid-state reactions - transport processes in diffusion-controlled corrosion reactions - the corrosion of silver by liquid sulphur - the high temperature corrosion of metals and alloys in complex aggressive environments. The nature of fast-ion-conductors, the operative transport mechanisms and the applicatioins for which these the unique properties of theses materials are essential Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details* CH4602 Module Code* Module Name* ECTS Weighting* MATERIALS CHEMISTRY 2 5 Semester/term Semester 2 taught* Contact Hours* 18 hours Lectures Module Personnel Learning Outcomes Module Learning Aims CH4006/CH4064 - Photochemistry Module Content/ Description* Introduction (1 lecture). Absorption of light. Selection rules and transition probabilities. Singlet states: (2 lectures) Fluorescence, quantum yields, lifetime measurements, radiationless processes. Jablonski diagram. Transient Spectroscopy: (1 lecture). Fluorescence lifetime determination: laser flash photolysis. Triplet states: (1.5 lectures) nature, population, spin-orbit coupling, phosphorescence, energy transfer, reactions. Nanosecond and picosecond laster photolysis. Photoreduction of benzophenone and derivatives as an illustrative example of an organic molecule in solution (1.5 lectures). Another illustrative example of photo-reactions, e.g. Photo-induced electron transfer reactions or photochemistry of co-ordination compounds. CH4008/CH4061 - Advanced Physical Chemistry Electrochemistry: Classification, synthesis and fundamental properties of electroactive polymer materials. Ionic and electronic conductivity mechanisms exhibited by electroactive polymers. The experimental determination of electronic and ionic conductivity in electroactive polymers using microelectrode and complex impedance spectrosopic methods. The use of electroactive polymer materials as amperometric chemical sensor devices. Molecular Reaction dynamics: Potential energy surfaces and molecular reaction dynamics. P.E. Surfaces. H3. Attractive and repulsive surfaces. Molecular reaction dynamics. Monte Carlo methods. Reaction crosssection H + H2 reaction. Molecular Beams and I.R. Chemiluminescence. Molecular beam methods. Reactive collisions - forward, backward and sticky collisions. IRCL Technique. F + H2 D2; H + F2. Tunnelling; MRD & ACT. Recommended Reading List Module Pre Requisite Module Co Requisite Assessment Annual Examination Details*