HOW TO PREPARE THE PROJECT

1. Define the question(s)

2. Choose appropriate methodology

What is known about the strengths & weaknesses of the chosen methodology?

3. Do a literature search

Has the technique been sucessfully applied to related systems?

Are there experimental data or accurate calculations available for the same or similar systems?

4. Relate the project to your research (if possible)

Poster should have the following format:

Objective (overall goal)

Specific Aims (the question(s) & how they will be answered)

Significance (importance & relevance)

Background (literature references on methodology, previous applications to related systems, experimental data)

Methodology (describe procedure & computational techniques)

Results (tables, graphs, figures)

Discussion (Were you able to answer the question(s)? How qualitative/quantitative are the results? How do they compare to experiment or chemical intuition? What are possible extensions of the work? How do your results compare to the calculations of others (if applicable)?)

References

EXAMPLE: Semiempirical Quantum Mechanical Calculation of the HCOC Torsional Barrier in Dimethyl Ether

Objective: To compare the HCOC torsional barrier in dimethyl ether calculated by semiempirical quantum mechanics to the ab initio torsional barrier of Venanzi and coworkers and to experiment

Specific Aims: To use the AM1, PM3, and MNDO methods to calculate the HCOC torsional barrier

Significance: The significance of this work is to test to see if the cheaper and faster semiempirical methods can give an accurate torsional barrier. If so, then these methods could be used for torsional studies on similar systems

Background: Halogenated ethers are an important class of inhalation anesthetic. There exists a considerable body of structure-activity data which relates the change in molecular formula to anesthetic potency, as measured by administration of the ether to a mouse in a jar [1]. It has been shown that halogenated ethers inhibit the firefly luciferase enzyme [2]. This gives some support to the idea that these compounds may bind to a specific protein site as part of their mechanism of action. In order to study the molecular recognition process at the molecular level, in the absence of knowledge of the protein receptor structure, it is useful to calculate the structure of the low energy conformers of these ethers, as well as molecular properties such as the electrostatic potential. Then it may be possible to determine a pharmacophore for anesthetic activity by relating the changes in molecular structure and properties of the anesthetic to the changes in its biological activity. Since there are over 150 compounds in the database, it would be relatively cheap and fast to carry out the conformational analysis using molecular mechanics. However, available molecular mechanics programs have not been parameterized for halogenated ethers. Therefore, Venanzi and coworkers have begun this parameterization study using a set of fluorinated dimethyl ethers. For example, Venanzi and coworkers [3] have used the 6-31G** basis set to calculate the HCOC torsional barrier in dimethyl ether. They found a barrier of 2.5 kcal/mol, which is close to the experimental barriers of 2.70 kcal/mol [4] and 2.72 kcal/mol [5]. However, since the AM1 [6], PM3 [7], and MNDO [8] semiempirical techniques are faster than ab initio calculations, it would be useful to see if they can give accurate results for this class of compounds. Fabian [9] found that the AM1 method often gave spurious results in torsional studies where the low energy conformers were influenced by lone pair-lone pair interactions. The purpose of this study is to test the AM1, PM3, and MNDO methods in calcilation of the HCOC torsional barrier for dimethyl ether.

Methodology: The SPARTAN program [10] was used to construct a starting structure of dimethyl ether and to carry out the semiempirical calculations. For dimethyl ether, C1H2H3H4O5C6H7H8H9, y and f were defined as: f = H2C1O5C6, y = C1O5C6H7. For each technique (MNDO, AM1, PM3), the geometry was optimized for fixed values of (y, f). The potential energy surface was explored by allowing y and f to vary in 30o increments. Plots were made of energy versus f for each y.

Results: The results of the MNDO, AM1, and PM3 calculations are shown in Figs. 1-3, respectively. The results show that......

(Graphs)

Discussion: Compared to the 6-31G** torsional barrier of 2.5 kcal/mol and the experimental barrier of 2.7 kcal/mol, the MNDO, PM3, and AM1 barriers...... (Also compare the semiempirical barriers to each other)

(Does the barrier agree with the ab initio and experimental results? Even if the semiempirical techniques do well in this case, they may not be accurate once fluorine substituents are added. Future work should investigate this.)

(Optional/additional studies could be: see the effect of solvent on the barrier by doing an AM1/SM2 calculation; calculate the electrostatic potential of different conformers--does it change much?)

References:

[1] F.G. Rudo and J.C. Krantz, Jr., Br. J. Anesthesia, 46, 181 (1974).

[2] N.P. Franks and W.R. Lieb, Nature, 310, 599 (1984).

[3] C.A. Venanzi, personal communication.

[4] P. Groner and J.R. Durig, J. Chem. Phys., 66, 1856 (1977).

[5] U. Blukis, P.H. Kasai, and R.J. Meyers, J. Phys. Chem., 38, 2753 (1963).

[6] M.J. S. Dewar, E.G. Zoebisch, E.F. Healy, and J.J.P Stewart, J. Am. Chem. Soc., 107, 3902 (1985).

[7] J.J.P. Stewart, J. Comput. Chem., 10, 209 (1989).

[8] M.J.S. Dewar and W. Thiel, J. Am. Chem. Soc., 99, 4899 (1977).

[9] W.M. F. Fabian, J. Comput. Chem., 9, 369 (1988).

[10] SPARTAN, available from Wavefunction, Inc., Irvine, CA