CHEM2203: Reaction Mechanisms in Chemical and Biological Systems

Course Organizer: Dr M J Porter

Lecturers: Dr M J Porter, Dr T Sheppard, Dr S Howorka

Normal prerequisite: CHEM1201

Units: 1/2

Moodle page:


The aims of this course are to give students an insight into the methods by which organic reaction mechanisms are studied, and 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. Kinetic vs Thermodynamic control

Kinetic studies
Molecularity and order of reaction. Rate equations.

Acids and bases
The pKa scale and its meaning; pKas of common acids; the Henderson-Hasselbalch equation. Factors determining acid strength. 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.

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.