Molecular Modelling for Organic Chemistry

Importance of Molecular Modelling

The 1999 Nobel Chemistry Prize was awarded to Ahmed Zewail for his work in developing spectroscopic methods for studying reactions and in particular transition states, an essential aspect of molecular modelling.

Modelling is an essential component of the Grand challenge of Dial-a-Molecule.

Course Aims and synopsis

1. Molecular visualisation
2. Methods for Equilibrium and transition state geometry location
3. Introduction to Molecular mechanics methods
4. Applications of Semi-empirical, ab initio and density functional molecular orbital methods
5. Methods for topological analysis of wavefunctions

The course does NOT deal with: excited states and photochemistry, hybrid (layer) models and inorganics.

The use of these tools is illustrated via the following case studies:

• Molecular visualisation: Using known nuclear positions or templates to construct a model.
• 1. The helical structure of DNA
  2. Environmentally Friendly Herbicides.
  3. Chiral Resolution using the Pirkle Reagent
  4. Nanotechnology and Molecular cavities: Molecular self-assembly of Nanobiotics, Dihydrogen bonding
• Molecular Mechanics and Conformational analysis: Calculating the Nuclear positions
• • 3 revisited: Where IS the H-bond in the Pirkle Reagent?
  5. The mechanism and stereochemistry of Carbocation rearrangements
  6. Design of organic crystals: A molecular anvil
• Reactivity using Quantum Mechanics: Calculating where the electrons are
• • 3 revisited: Where ARE the electrons in the Pirkle Reagent?
  • 2 revisited: How do orbitals interact within a molecule?
  • 4 revisited: The structure of DNA
  • 5 revisited: Non-classical Carbocations
• Mechanism determined using Quantum Mechanics
• 7. Regiospecificity: The mechanism of electrophilic aromatic substitutions
     • Nitration of Pyridine
     • Aryl C-C bond formation using a metal catalyst
  • 6 revisited: The Diels Alder reaction
  8. Stereospecificity: Asymmetric C-C bond formation via Enol Borinates.
  9. Stereospecificity in the Strecker amino acid synthesis.
  10. Stereospecificity in Catalytic polymerisation: The Ziegler-Natta mechanism and the role of agostic interactions

2011 Exam Paper and outline answer

Background texts and workbooks:

1. Wikipedia entry
2. Computational Organic Chemistry, Steven Bachrach, Wiley, 2007, ISBN 978-0-471-71342-5.
   • This book also has a very interesting Blog, where the latest news and interesting publications in the area are discussed.
   • Another blog on Computational Chemistry
3. Computational Chemistry Workbook: Learning Through Examples Thomas Heine, Jan-Ole Joswig, Achim Gelessus ISBN: 978-3-527-32442-2, 2009.
4. Essentials of Computational Chemistry, Chris Cramer, Wiley, 2002.
5. Chemical Applications of Molecular Modelling, Jonathan Goodman, RSC, 1999. (ISBN 0-85404-579-1)
6. Molecular Modelling Workbook for Organic Chemistry, W. J. Hehre, A. J. Shusterman and J. E. Nelson, 1998.
7. Brief Guide to Molecular Mechanics and Quantum Chemical Calculations, W. J. Hehre, J. Yu, P. E. Klunzinger and L. Lou, 1998.
8. Laboratory Book of Computational Organic Chemistry, W. J. Hehre, A. J. Shusterman, W. Wayne Huang, 1996.
9. Laboratory Exercises using HyperChem from Hypercube Educational Publications, M. L. Caffery, Caffery, Dobosh and Richardson. (ISBN 1-896164-30-7)
10. Molecular Mechanics across Chemistry. Anthony Rappe and Carla Casewit (ISBN: 0-935702-77-6).
11. Molecular Modelling. Principles and Applications, A. R. Leach, Longman, 1996. ISBN 0-582-23933-8
12. Introduction to Computational Chemistry, by Frank Jensen, Wiley, 1999 (ISBN 0-471-98425-6).
13. Introduction to Theoretical Organic Chemistry and Molecular Modelling by William B. Smith. ISBN: 978-0-471-18643-4
14. Encyclopaedia of Computational Chemistry, the definitive reference work for Computational Chemistry.
15. WATOC Congress, 1999, 2002, 2005, 2008, 2011.