CHEM2203: Reaction Mechanisms in Chemical and Biological Systems

Course Organizer: Dr M J Porter

Lecturers: Dr M J Porter, Dr T Sheppard, Prof A B Tabor

Normal prerequisite: CHEM1201

Units: 1/2

Moodle page:


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.

Course Structure

  • Lectures: 19 h
  • Tutorials: Workshops: 12 h
  • Labs: 0


  • Exam: 80 % (2 hours)
  • Lab: n/a %
  • Coursework: 20%

Recommended Texts

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

  • "A Guidebook to Mechanism in Organic Chemistry", P Sykes, Longman, 1986
  • “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.

Course Outline

(A) Organic Mechanisms (15 lectures, 5 x 2 h 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.

Kinetic studies
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. 

Ester Hydrolysis Mechanisms
Acid and base-mediated hydrolysis of esters; classification of different mechanisms.

Rearrangements and migrations
Cationic rearrangements; Baeyer-Villiger and Beckmann rearrangements; migratory aptitudes.

Crossover experiments
The basis of crossover experiments; examples in the Fries and Claisen rearrangements; ozonolysis.

Workshop 1: Rate Laws
Use of kinetic data to determine mechanism. 

Electronic Effects on Reaction Mechanisms
Electronic effects; linear free energy relationships; Hammett plots; the significance of σ, σ+ and ρ.

Isotopic labelling
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.

Solvent effects
Why the solvent can be important in determining rate; effect of solvent on nucleophilic substitution and other reactions.

Steric Effects
Steric effects on rate; steric acceleration and steric retardation. Reactions of substituted cyclohexanes.

Workshop 4: The Favorskii rearrangement

Use 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.

Radical reactions
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 x 1 h 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.