Expt ME 1

Molecular Energy (ME) Comparisons using Molecular Mechanics

Objective The purpose of this experiment is to use CAChe (Computer Aided Chemistry) molecular modeling software to compare the steric energies for groups of isomers. Note the software in use changed in 2008 to Scigress. Scigress is a new version of CAChe with slight modifications so as you read directions if a step doesn’t work exactly as written then you will need to try a logical alternative or alternatives - please record any variations on these pages and share with instructor. Please consider any trial and error as part of the fun and challenge of the experiment.

In this computational chemistry experiment, you will learn more about molecular mechanics and the contributions to steric energy in groups of isomers. Based on your chemical experience in organic chemistry, you may have an intuitive feel for which isomer has lower energy due to less steric strain. For each group of isomers, you will make a prediction and then test it with a molecular mechanics calculation. Since the isomers are very similar, the steric energy that is calculated from mechanics can be used to compare the energies of the structures. It would not be appropriate to try to compare the steric energy values for two rather different molecules because there is no absolute meaning to the number. However, by comparing similar molecules you can explore the contributions to molecular energy.

Report Instructions

Prior to starting your CAChe (Scigress) work, draw the isomers in each group side by side on a page. Put them in same order (left and right) as they were presented, and draw a circle around the isomer you expect to have the lower steric energy. Show your instructor that you have made a prediction for each group before you start your calculations. Your prediction doesn't have to be correct, but you must make a prediction. You must do this before you proceed with your CAChe calculations.

Below the structure of each molecule write the total steric energy from the Mechanics calculation. Below this write a side-by-side summary (vertical list) of the individual force field Expt ME 2 components in the same order as they are given in the CAChe Mechanics calculation. These include such factors as: stretch, stretch bend, improper torsion, bend-bend, electrostatics, angle, dihedral, torsion stretch, van der Waals, and hydrogen bond. At the bottom of the page, in a few sentences, clearly indicate the primary sources of high steric energy or strain (distortions from idealized parameters) for the higher energy isomer. In other words, indicate that portion or portions of the molecule where bond distances, bond angles, or torsional angles are strained and contribute to the higher total steric energy of the molecule. Discuss specific sources of strain in a molecule and why one molecular structure would be at lower energy than another.

Each partner will do all the work individually. Do your work separately. Your report will include a cover page and four additional pages–one page for each group of molecules with a summary of the main differences in energy at the bottom of each page.

CAChe Instructions You will work with four groups of molecules (groups 1, 2, 3, and 4) shown on a separate page. In the style used in the molecular drawings, when a line ends or two lines meet it represents a carbon atom unless labeled otherwise. And each carbon has the appropriate number of hydrogen atoms attached.

Getting Started If using a computer in the chemistry computer lab, move the mouse to start. The computer should already be turned on. Enter your Username and password for your OneNet Account and click OK. When you are done at the end of the lab, be sure to choose Log Off option from Shut Down, but do not turn off computer.

Open My Documents Folder (located on the desktop) and create a new folder with your name. Under File choose Open and choose New Folder. Anything you save must be placed in your folder only. Do not save any CAChe file in any other place than in your named folder!

Expect files to be purged at the end of each semester. If you need a permanent copy beyond that time you need to save to your MocsNet account or on a flashdrive. Expt ME 3

You can think of CAChe as a three-step process that includes: drawing a molecule, carrying out a calculation experiment, and observing the results of the calculation experiment.

Double click on the CAChe Workspace to open it. Enlarge workspace window.

Drawing a Molecule Make sure that you select not only appropriate atom, but also correct hybridization, charge, and bond. The box with charge specified for a neutral atom will be 0 or simply blank. For details of how to use the CAChe software to draw the structures, you will need to refer back to the CAChe tutorial or other CAChe experiments in this lab manual. Keep in mind that you should go to the fragment library to pick up structures like a benzene ring or cyclohexane ring. Don't try to draw those structures atom by atom. Do not to save any molecule into the Fragment Library folder! Only save into your own named folder. Also, atoms not shown in the list of atoms after Atom Tool is selected can be obtained from the Periodic Table option.

With each new molecule drawn, you always need to center and size molecule by pressing Control and f key. Every time you draw a new molecule you should make this selection and then you should rotate and observe the structure from different angles to make sure it is draw correctly. If you don’t rotate the molecule to look at in three-dimensions, you cannot really be certain what structure you are observing.

You can use Select Tool to draw a box around items or click on item to highlight. You can then remove the highlighted item by use of delete key on keyboard. You can immediately correct mistakes by choosing Undo under Edit on menu bar. The Select Tool (on Tool palette) can be used to click on a single atom or bond or to draw a box around a collection of atoms that can then be removed by striking the delete key or using the Cut or Clear choices under Edit menu.

Draw your first molecule of interest as you learned to do in the tutorial and save molecule by appropriate name in your named folder you created. Now click once on the background behind Expt ME 4 your molecule. At this point the molecule without hydrogen atoms should appear as a highlighted solid ball and stick model on the screen. Under Beautify on the menu bar, choose Valence to add hydrogens and any unpaired electrons. If you wish you can view electrons (from menu bar choose View – Show Electrons).

Hold down Ctrl key and strike f key to center and size molecule. Choose Rotate from Tool palette and rotate molecule to observe from various angles. Every time you draw a new molecule you should do Ctrl f and rotate to carefully observe the three-dimensional structure of the molecule. Select views: Lines Only, Lines, Ball and Cylinder, and Space Filling to see how the molecule looks in different views. Rotate each view. Then return to normal ball and cylinder (or ball and stick) view. You don't need to print a copy of the molecule.

To save the molecular structure, under the File Menu select Save. When box of places to save appears, go to the desktop and open My Documents folder and then open your named folder. You must save your files only in your own named folder. CAChe will use this file in later calculations. You can use the full name of molecules for their files but not more than 31 characters.

Keep in mind that although the comprehensive Beautify–Comprehensive option is appropriate for many structures, there are times when Beautify might change your structure such as converting a cis to trans so that you may need to lock a portion of the molecule (highlight atoms with Select Tool and then Adjust – Lock). The locked atoms will not move so that the arrangement of atoms in that portion is not changed. After beautifying the molecule with a portion locked, then you can unlock the atoms and go to mechanics to optimize structure. For example, to lock atoms across a double bond in place, choose Tool–Select Tool. Click on atom 1 and you should see it become darker. With the shift key held down, click on atoms 2, 3, and 4 in sequence. The four atoms should all become darker. Let up on the shift key and select Adjust – Lock. You have now locked the geometry so the structure will stay in its current geometry with respect to the double bond. Now you can Beautify–Comprehensive structure and save it. You will need to unlock prior to running mechanics so that optimal structure can be found from the Beautified starting point. When you run “New Experiment” it does not change the basic starting Expt ME 5 structure (for example, cis will remain cis) but it does move atoms by changing bond lengths and bond angles, for example.

Molecular Mechanics Calculation and Observing Results

Part I – Getting started Prior to starting the calculations for the groups of molecules, do the following to practice CAChe and help understand Molecular Mechanics. You should refer to the CAChe tutorial in the Appendix to help remind you of any details of how to use CAChe. Place a sp3 carbon atom on the screen and then select beautify. You should observe a methane molecule. Use control-f to center and size. Change to space filling view. Rotate molecule. Change to ball and stick view. Rotate molecule. Delete one of the hydrogen atoms. Draw it again but at a much greater distance. Place a bond length label on this C–H bond. Move the hydrogen atom to a distance of about 15 angstroms from the carbon. This distance is the nuclei separation.

Under Experiment on the Menu Bar, choose New. It will ask you to save the molecule if you have not already done so. Save into your folder with name methane. Once you have done so, an experiment window will open. Select the following choices. Property of: chemical sample, Property: optimize geometry, Using: MM3. Start the calculation. Observe results when calculation is done. Scroll through screen to observe how total energy changes with each iteration of atom positions. Observe the window with the methane. What has happened to the C–H bond distance? Mechanics does a series of calculations where the bond distance is changed and calculates a new energy at each new atom position. How has the total energy of the molecule changed as the C–H bond distance was changed.

The Mechanics calculation is a classical calculation. The program considers the molecule to be a collection of spherical atoms connected by spring-like forces. The program finds the minimum energy confirmation (optimal structure) by minimizing the energy associated with the stretching, bending, and twisting forces of the forces holding the atoms together. Beautify approximates the best bond distances and angles and then mechanics calculates the energy and changes positions Expt ME 6 to see if a lower energy can be found. Atom positions are continued to be changed until the lowest energy is found. If it is the absolute lowest possible energy, it is called the global minimum. If it is lower than nearby structural possibilities but not the absolute lowest, it is called a local minimum. To find the best structure of a molecule, it is desirable to achieve the global minimum.

Part II - Molecule groups Open a new window. Draw your first molecule. Size, rotate, etc. to make sure you have the three-dimensional structure you want. Save molecule with appropriate name such as “molecule1A” in your named folder. Under Experiment on the Menu Bar, choose New. It will ask you to save the molecule if you have not already done so. Once you have done so, an experiment window will open. Select the following choices. Property of: chemical sample, Property: optimize geometry, Using: MM3. Start the calculation. Observe results when calculation is done. Scroll through screen to observe how total energy changes with each iteration of atom positions.

At the bottom of the window, you should observe energy values for such factors as: stretch, stretch bend, improper torsion, bend-bend, electrostatics, angle, dihedral, torsion stretch, van der Waals, hydrogen bond, and the total energy of final structure. Record all these values under the structure you have drawn on the page. Continue the procedure above with other molecules.

Note that we are able to compare these steric energies for molecule groups only because we have two nearly identical molecules. The steric energy does not have any absolute meaning in comparing different molecules. So it would make no sense to for example compare the steric energies of methane and ethane. But we could compare different conformations of ethane as we rotated around the C–C single bond to see if the eclipsed or staggered form was lower energy.

Note: If the energy of any of these molecules is above 100kcal/mol then you probably made an error in the drawing or conformation and need to redo.

Expt ME 7

GROUPS OF ISOMERS TO BE COMPARED