CHEM2203: Organic and Biological Reaction Mechanisms
Course Organizer: Dr T Sheppard
Lecturers: Dr S Howorka, Dr T Sheppard
Normal prerequisite: CHEM1201
Course evaluation: 2009/2010 (pdf)
Moodle page: http://moodle.ucl.ac.uk/course/view.php?id=4431
The aims of this course are to give students a better insight into the methods by which organic reaction mechanisms are studied, as well as to broaden their knowledge of reaction mechanisms in both enzymic and non-enzymic systems.
By the end of this course you should:
- Understand the various methods which are used in elucidating reaction mechanisms.
- Be able to interpret the results of kinetic, labelling, and other mechanistic studies.
- Understand the meaning of linear free energy relationships, and know the meaning of the parameters σ and ρ.
- Be able to derive the Michaelis-Menten equation, and understand the significance of kcat and KM.
- Understand the rationale for the catalytic properties of enzymes, and know several representative mechanisms of catalysis.
- Recognise the differences between organic and enzymatic catalysis.
- Lectures: 22
- Tutorials: Workshops: 12
- Labs: 0
- Exam: 80 % (2 hours)
- Lab: n/a %
- Coursework: 20%
As a main textbook, we recommend you use
- “Organic Chemistry”; J Clayden, N Greeves, S Warren, P Wothers, OUP, 2000 - in particular chapters 5, 13, 41 and 50.
For more specialised information, try
- “Structure and Mechanism in Protein Science”; A Fersht, Freeman, 1999
- “Fundamentals of Enzymology”; N C Price, L Stevens, Oxford, 3rd Edn., 1999
- “An Introduction to Enzyme and Coenzyme Chemistry”; T Bugg, Blackwell , 2nd Edn., 2004.
(A) Organic Mechanisms (15 lectures, 5 workshops)
What is a mechanism? Why should we study mechanisms? Concerted vs. stepwise processes; transition states and intermediates; molecularity. Early and late transition states; the Hammond postulate. Catalysis.
Rate equations and their integrated forms; measuring rates and rate constants.
Acids and bases
The pKa scale and its meaning; pKas of common acids; when to draw protons in a mechanism - and when not to; specific and general acid and base catalysis.
Acid and base-mediated hydrolysis of esters; classification of different mechanisms.
Cationic rearrangements; Baeyer-Villiger and Beckmann rearrangements; migratory aptitudes.
The basis of crossover experiments; examples in the Fries and Claisen rearrangements; ozonolysis.
Workshop 1: Rate Laws
Use of kinetic data to determine mechanism.
Effects on Reaction Mechanisms
Electronic effects; linear free energy relationships; Hammett plots; the significance of σ, σ+ and ρ.
Use of labelling to track the fate of individual atoms.
Workshop 2: Ester hydrolysis
Use of isotopic labelling and Hammett plots, together with kinetic studies to determine a variety of ester hydrolysis mechanisms.
Kinetic isotope effects
Origin of the kinetic isotope effect (KIE); use of the KIE to unravel mechanism.
Workshop 3: Kinetic isotope effects
Use of Kinetic isotope effect information to support/exclude proposed reaction mechanisms and to identify the rate determining step.
Why the solvent can be important in determining rate; effect of solvent on nucleophilic substitution and other reactions.
Steric effects on rate; steric acceleration and steric retardation. Reactions of substituted cyclohexanes.
Workshop 4: The Favorskii rearrangement
of kinetics, labelling and linear free energy relationships to deduce the mechanism
of the Favorskii rearrangement
Observation of intermediates
Direct observation of intermediates; trapping of intermediates.
Structure, stability and formation of radicals; radical chain reactions and their kinetics; direct observation of radical intermediates.
Workshop 5: The benzidine rearrangement
Using all of the techniques seen to date to elucidate the mechanism.
(B) Enzyme Mechanisms (5 lectures, 2 workshops)
Overview of protein structure. Principles of catalysis including transition state, general-acid-base catalysis, entropy, and covalent catalysis. Enzyme kinetics with specific reference to Michaelis-Menten kinetics. Measurement of enzymatic rate constants. Structure and mechanism of selected enzymes. Enzyme inhibition and allosteric regulation.