While we wait for everyone to arrive, please jot down your syntheses numbers for weeks 1 and 2. Your protocols can be pi

1. While we wait for everyone to arrive, please jot down your syntheses numbers for weeks 1 and 2. Your protocols can be picked up from the lab before you leave.

2. While we wait for everyone to arrive, please jot down your syntheses numbers for weeks 1 and 2. Your protocols can be picked up from the lab before you leave.

3. Introduction to Molecular Modeling

4. The 1998 Nobel Prize in Chemistry Walter Kohn, UC Santa Barbara "for his development of the density-functional theory“ John Pople, Northwestern "for his development of computational methods in quantum chemistry" “Chemistry is not only test tubes and chemicals. In quantum chemistry, quantum mechanics is used to compute the properties of molecules and their interaction. This year's laureates have made it possible to use the complex equations of quantum mechanics to study molecules and chemical processes with the help of computers.” - from the Nobel Press Release http://nobelprize.org/nobel_prizes/chemistry/laureates/1998/illpres/computers.html

5. Applications • Academic Research • models to explain chemical phenomena at the molecular level • Protein folding • Active sites of enzymes • Industry/Pharmaceuticals • drug mechanism and/or metabolism • product improvement Avoid costly experiments ($, time, safety)

6. Objectives for today…what kind of information can you obtain from molecular modelling? Stick Space filling Tube Ball & Stick (Simple Pictures/Not realistic representations) • • Structure (bond lengths, bond angles, & molecular geometry) • • Energy (enthalpy of formation & MOs) • • Reactivity (electron rich or poor parts of the molecule & dipoles) • • Spectroscopic properties: Vibrational (IR) • *(UV-Vis) & (NMR) also possible, but not done today

7. More realistic picture with electrons from all occupied molecular orbitals

8. Where you start. Hartree-Fock models useful for predicting structure, energy and property calculations, in particular for organic molecules

9. ĤΨ = εΨ Two energy forms must be accounted for: 1) Potential energy • Electrostatic attraction b/w electrons & nucleus (usual view of bonding) • Electrostatic repulsion b/w nuclei • minimize by finding equilibrium bond length 2) Kinetic energy • e- movement • minimize by allowing for delocalization in a larger space (i.e. create an MO larger than the AO) Total energy is the heat of a hypothetical reaction that creates a molecule from a collection of separated nuclei and electrons.

10. 3-21G ab initio Hartree- Fock calculation Schrodinger equation ĤΨ = εΨ describes molecules in terms of motions and interactions of nuclei and electrons solvable for a 1-electron atom only use approximations to simplify the equations to be solved Born-Oppenheimer Approximation nuclei >>> electrons nuclear kinetic energy = 0 Hartree-Fock Approximation electrons move independently of each other In the calculation, one electron is selected and the Schrodinger equation is solved in the presence of a field (replacing individual e-e interactions) containing the remaining electrons. This is repeated for each electron until convergence. Ab Initio from the beginning, without empirical data

11. MO-LCAO: Molecular Orbital – Linear Combination of Atomic Orbitals Atomic Orbitals just mathematical functions {e.g., Ψ1s = 1s = ce-Zr/a◦} Basis Set: Atomic orbitals approximated by Gaussian functions (easier to  ) 3-21G basis set 3 represents the number of functions used to construct core atomic orbitals. The basis set is divided into core and valence sets of Gaussian functions describing all of the electrons. {These two functions are different because they have different exponent arguments (ζ).} f(r) = ae-ζr2/a◦2 “Two – one” describes the number of functions summed to construct the valence atomic orbitals.

12. HOMO & LUMOelectron pair donor/acceptor orbitals The exercise will ask you to analyze the HOMO of two ligands and determine the preferential site of attack.

13. Highest Occupied Molecular Orbital Lowest Unoccupied Molecular Orbital HOMO & LUMOelectron pair donor/acceptor orbitals“frontier orbitals,” important for chemical reactions What sort of orbital is this? + – – – + + Delocalized π* LUMO of formamide

14. What are the limits of your chosen model? • Hartree-Fock models tend to overestimate energies and underestimate bond lengths. Methods exist to correct HF calculations. • IR frequencies tend to be 12% higher than experimental values. • No single method is ideal for all applications. • Models and basis sets are chosen based on the properties, problems, level of confidence, and practicality. • Improved technology allow for advances in modeling.

15. Some final reminders… Do the examples in pairs and then individually do the exercises to be turned in. The updated Spartan ’08 info is on the course website. It remains largely the same as what is in your manual for ‘06. The online info contains a copy of the report to be completed. Info can be cut and pasted into the document, printed, and turned in. The department has 15 licenses, so if your calculation fails at first, try again. Pick up protocol for first synthesis before leaving!