Lab1: Introduction to Computational Chemistry

Primary Learning Objectives By the end of this lab, students should be able to:

Give a general overview of computational chemistry. Understand the difference between Molecular Mechanics, Semi-Empirical, and Ab Initio

methods. Understand the difference between a local minimum and a global minimum. Understand that large molecules can have different potential energies depending on bond

rotations. Use Spartan software to construct simple organic molecules.

Background Computational chemistry is the use of mathematical formulas and methods to calculate the properties of chemical compounds and systems. Computational chemistry has been around for many decades, but in the past few years, computers have advanced to the point where computational chemistry is widely accessible. Pharmaceutical companies have especially taken advantage of the benefits of computational chemistry. A pharmaceutical company evaluates many chemical structures. The cost of developing a new medicine can exceed 1.5 billion US dollars. The ability to predict the properties of many compounds quickly without running lab trials can save time and money. Computational chemistry makes approximations based on formulas and/or experimental data. There are many methods used that vary in their accuracy and computational cost (processing power needed to perform the calculations). However, most fall within three main categories.

Molecular Mechanics treats atoms in molecules like balls attached by springs. This

method uses physics based formulas and calculations. It has the lowest computational cost and is often used for very large molecules or systems of molecules. Molecular mechanics is not useful for calculating electronic properties.

Semi-empirical methods use a combination of quantum physics calculations and

experimental data. This method is more rigorous than molecular mechanics, but also requires more computational processing. It is useful for medium sized systems and is capable of producing electronic data as well. Semi-empirical methods use data from a group of molecules called a basis set. The more similarities between the system being measured and the basis set, the more accurate the calculations will be.

Computational Cost – A measure of the quantity and complexity of the calculations performed. Higher computational cost usually means a need for more computing power (bigger faster computer processor) and/or more time to complete calculations.

Ab Initio methods use only quantum physics calculations. It is the most rigorous type of

method, but also has the highest computational cost. This type of method is most useful for smaller systems that require the best available accuracy.

Local vs. Global Minimums – Optimizing the geometry of a molecule (finding the

position of atoms in a molecule that give the lowest potential energy) is one of the many functions of computational chemistry. The software will slightly adjust the bond angles, lengths, and rotations until adjustments in any direction results in a higher calculated potential energy. One thing that anyone working with computational chemistry must realize is that what the software actually predicts what is called a local minimum. There can be several local minimums, but there is only one global minimum.

Figure 1 - Consider a ball in the system represented above. The ball will roll to the low spot nearest to where it starts. However, this may not be the lowest possible spot.

Dihedral Angles A dihedral angle is the relative position of groups of atoms within a molecule as they rotate around a single bond (see Figure 2). If you will remember from General Chemistry, atoms can rotate around single bonds, but not around double or triple bonds. The concept can be illustrated with something called a Newman Projection (see Figure 3). Larger molecules can have many dihedral angles.

Figure 2: For the butane pictured above, the dihedral angle is the relationship of the two -CH3 groups when the observer looks

along the -CH2-CH2- bond.

Figure 3: Newman projections of butane. The projection on the left represents a dihedral angle of 0˚ and the projection on the right (middle image) represents a dihedral angle of 180˚.

Procedure Before you start the first lab, you should have completed the Spartan tutorial. If you have not, open Spartan Student and then click on the Activities menu selection on the upper right hand side of the screen. Under activities, click Tutorials. A tutorials screen will come up. You should complete the Walking Through Spartan and Building Organic Molecules in 3D tutorials.

Part 1: Local and Global Minimums for Acetic Acid In this section, you will be calculating the comparative energy levels of various configurations of acetic acid. Although the bond angles of a compound will stay relatively the same, molecules with several or more atoms can have different configurations (shapes) because of the ability of single bonds to rotate (see figure 2).

Figure 4 - Acetic acid can take on different conformations as the -OH group rotates around the C-O

bond. The C-C bond can rotate as well, but is shown stationary for simplicity.

Different conformations of a molecule will have a different total energy. The variation in energy comes from steric interactions (molecules pushing away from each other as the electron clouds overlap) and attractions or repulsions caused by intramolecular dipole interactions. The purpose of this portion of the lab is to graph the relative energy of acetic acid as the –OH group rotates similar to what is depicted in Figure 4.

Open Spartan Student and in the menu options, click File – New Build in the menu. 1. Build an acetic acid molecule as shown below.

CH3C

O

OH

2. In the menu options, click Build – View and then Build – Minimize.

3. In the menu options, click Geometry- Constrain Dihedral. 4. Click the O-C-O-H atoms as highlighted in blue below.

CH3C

O

OH

5. After the four atoms are highlighted, a lock button will become available at the bottom right of the screen. Press the Lock button and then click the Profile checkbox that is to the right of the Lock button.

6. Once the lock button is pressed, three boxes will be available in-between the Lock button and the Profile checkbox. Use the two left boxes to set the range from 90˚ to 450˚. Type 90 in the left side box and then type 450 in the middle box. Finally, type 37 in the right side box and press Enter. You have just completed setting up a profile. In this particular case, the OH-C bond is set up to rotate from 90˚ to 450˚ at 10˚ intervals.

7. In the menu options, click Setup – Calculations. A Calculations dialog box should appear.

8. In the Calculate section, choose Energy Profile in Gas with PM3. 9. At the bottom of the Calculations dialog box, uncheck Global Calculation and the press

Submit. 10. Spartan Student will prompt you to save your file. Name and save your file on your

own flash drive. Do not leave your files on the lab computer. 11. Once you press save, a dialog box will confirm that the calculations have started. The

calculations are complex and can take a few minutes to complete. You will be notified when the calculations are complete.

12. Once the calculations are complete, you will be asked if you would like to open the new document. Click Yes.

13. Once the new file opens, you will be able to see at the bottom left of the screen two tabs indicating that you have two files open. You will also see what looks like play, forward, and reverse buttons. If you press the forward button, you will notice that you actually have 37 different molecules, each with a slightly different rotation of the OH-C bond.

14. In the menu options, click Geometry – Constrain Dihedral. Pick the same four H-O-C-O atoms as before. At the bottom right of the screen, you will see a down arrow next to the Lock button. Press the down arrow. This loads all of the angles into a spreadsheet that you can access.

15. In the menu options, click Display – Spreadsheet. A spreadsheet should come up with all of the angles you loaded in the left column.

16. Click on the top row to select the 90˚ constraint. Click the Add button at the bottom. A dialog box will come up. Choose the Molecule List tab at the top and then press the Relative Energy button.

17. You should now see two columns of data in your spreadsheet. Select and copy the data from the spreadsheet into Excel.

18. Look through the data in Spartan Student. Find any minimums (places where the energy is higher before and after). When you see a minimum, click on that row in the spreadsheet. After you click on the row, the conformation that goes with that row should show in the background. Save a picture of all of the minimums, there should

be two. To save a picture in the menu options, click File – Save Image As. Name your image and click OK for the image size. Before you save the image, make sure your molecule is positioned for good viewing. If the spreadsheet is blocking the molecule, you can move the spreadsheet to the side. Include images of the two minimum energy configurations.

19. At the bottom left of the screen, click on the tab for the original acetic acid molecule that you built.

20. Also at the bottom middle of the screen, there is a dropdown box that should say “acetic acid.” Click in the dropdown box and then click Replace. This switches out your molecule for a fully optimized molecule from the Spartan library. It is not necessary to do this, but it will make the next step quicker.

21. In the menu options, click Display – Surfaces. 22. In the Surfaces dialog box, click Add – electrostatic potential map. Spartan will

calculate for a few seconds and then a check box will appear beside electrostatic potential map in the list. Click the checkbox and close the Surfaces dialog box.

23. Save a picture of the electrostatic potential map for acetic acid for your report. If you want to see the atoms under the surface, follow these steps:

a. Click anywhere on the Electrostatic Potential Surface b. In the menu options, click Display – Properties. c. In the upper right of the Properties window, you will see a label called Style

with a drop-down box below that says Solid. Click the dropdown box and choose Transparent.

d. Close the Properties window. You should now be able to see the molecule beneath the surface.

24. Be sure to save your work before exiting Spartan Student. 25. In Excel create a graph from your data with the dihedral angle on the x-axis and the

relative energy on the y-axis. Use the correct units for energy. The graph should be included in the lab report with proper labeling and a caption.

Part 2: Find the Local and Global Minimums for Ethanedial

C CO

H

O

H

Using a procedure similar to what you did in part 1, create a graph of relative potential energy vs. dihedral angle for ethanedial (pictured above). Include your graph in your lab report along with a picture of your lowest and highest potential energy conformations. Use the line of atoms highlighted in blue for the dihedral angle.

Questions for Understanding 1. List all of the angles that are minimums for acetic acid. Which angle is the global

minimum and which one is just a local minimum? 2. Based on what you have learned, how can the starting configuration of your molecule

impact the optimized geometry? For example, with acetic acid, if you started at an H-

O-C-O dihedral angle of 120˚ and then started at a dihedral angle of 320˚, would you expect the software to calculate a different optimum geometry? Look back at your graph and Figure 1 caption to help you understand.

3. Research the advantages and disadvantages of computational chemistry and compare the two.

4. Look at the picture of the electrostatic potential map for acetic acid. This surface indicates the electron density around the various atoms in acetic acid. Blue areas have lower electron density (more positive) and red areas have higher electron density (more negative). You have probably learned about intermolecular attraction, but it is also common for larger molecules to experience intramolecular attraction (atoms within a molecule attracted to each other). Using the electrostatic potential surface (ESP), explain why the global minimum for acetic acid has the hydrogen positioned next to the C=O oxygen. Include a picture of your ESP as an illustration for your answer.

5. For ethanedial, explain the results of your energy profile calculations. You should reference you graph and figures. Your explanation should include information regarding how steric interactions (atoms getting close enough to overlap their orbitals) and intramolecular attractions and repulsions affect the relative energies of the various conformations.