Clickable Contents:
1. Why?
1a. McBride's Computational Chemistry Philosophy
2. What Chem3D does
3. Where it is Available
4. Viewing and Measuring
5. Calculating and Minimizing Energy
6. Creating Models
7. Problems

First we would like to learn about molecules, or more properly about one type of model of molecules. There are many other types of models: quantum mechanical calculations, 3-dimensional plastic or ball-and-stick models, the 2- (or 3-!) dimensional pictures we draw on paper or see in books, and the picture we conjure up in our heads when we think about molecules. Computer-based "molecular mechanics" models, closely analogous to Chem3D are among the prettiest and most dramatic. They have become widely available and are key elements in much current research - particularly in computational biophysics and biochemistry.

Second, we need to get a feeling for the basis and reliability of this kind of computer model, its origins, its assumptions, how it works (at least vaguely), and how well it works both

- for organizing and reproducing the data it was derived from and
- for predicting new independent data.

This is a tall order, and we will only barely scratch the surface.

Click here for some Philosophy on the roles of Computation, Experiment, and History in Organic Chemistry.

Chem3D is a program with many parts. The two most relevant functions for our present purposes are the following:

(1) to create and display images of molecular models in ways that communicate the arrangement of atoms in space to the user

(2) to calculate their energy and minimize it by adjusting the atomic positions using "Molecular Mechanics" (not quantum mechanics).

Later on we may use it to study the motion of atoms in molecules (one can also do this with MacSpartanPlus).

There are three versions of Chem3D : fully configured Chem3D Pro (an old version for Macs available on Yale Mac clusters), Chem3D Ultra 8.0 (a free trial version that expires two weeks after you install it on your PC), and Chem3D ActiveX Net 8.0, which is free but won't do everything. The last two versions for Windows only can be installed on your own PC from the Camsoft commercial web site:

One disadvantabe of the Net freebie is that it cannot calculate energies for molecules with more than 6 non-hydrogen atoms.

When you want to do things that the Net version won't allow, you can use the Pro version from a networked Mac or the Ultra version. Yale owns 5 licenses for the use of Chem3D Pro, meaning that 5 individuals may use the program simultaneously.

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The following instructions are a couple years old. I haven't tried them on the Windows versions of the program, but I hope they are easily adapted. I hope to have time soon to modify the instructions. If there is something you and your friends are unable to do with the version you are using, let me know and I'll send a help message

First familiarize yourself with the viewing and measuring features of the program by examining several structures with the Net vesion. It is not hard to build your own molecule, but you mightbegin by examining anti-butane (You have to download it to your machine, it might be as easy to just build your own. Other prebuilt structure are in the Materials portion of the course web site after you've logged in as student. I'm working on making more files available).

Launch Chem3D Net

Open the desired structure (File, Open, anti butane)

When the structure comes up, observe it by dragging the cursor (hand) up and down in the right margin and back and forth in the bottom margin. Try the trackball (chosen by clicking on its icon below the arrow at the top left of the screen). Move the hand around within and outside the circle to get a feel for this tool. If the structure goes off the screen, choose Size All Views under the View menu to shrink it. Use the tool to get views along different bonds (these are related to the "Newman Projection", text p. 76).

Under the Windows menu choose preferences and experiment with different Model Types (after clicking the button to indicate a particular model type, click the main screen to see the model). Try out the other options under Preferences.

Ulitmately the highlight of your tour will be to choose Stereo Views under Preferences and watch in stereo as you maneuver the model with the trackball. We will soon issue stereo glasses, but you might be able to shrink the screen so the images aren't too far apart to preclude viewing in stereo without glasses. If you have difficulty, as you probably will at this point, just turn off Display Stereo Views.

An alternative to stereo viewing is to make a rotating molecule movie as follows. Under the View menu choose Spin (about the y axis - or another axis). After the image has spun a bit click the stop sign in the little Spin window. Then go back to the View menu and select Jiggle. The program calculates a number of frames between the last two orientations shown and then smoothly rotates back and forth through them. You'll like this.

PROBLEM 1: NOTE WHAT METHODS CAN BE USED TO SHOW THREE- DIMENSIONAL INFORMATION, THINK OF AS MANY AS YOU CAN.

Choose the selector tool by clicking on it at the top left of the screen and use it to identify atoms just by pointing to them. Point to a bond to identify its atoms, display its bond type, and measure the distance. Highlight one atom by clicking on it and use the arrow to measure distances to other atoms. Then highlight a bond by clicking on it and use the arrow to measure angles to other atoms. You can also select a pair of atoms, or bonds, by shift-clicking on them sequentially. Select two successive bonds and use the pointer to measure angles of twist (torsional angles) to other atoms.

Try orienting the model by the following techniques. Choose a bond (click on it) and under the View menu move it to different axes. Choose a pair of bonds (shift click) and under the View menu move them to different planes.

Choose a bond and move the cursor (hand) back and forth in the top margin and up and down in the left margin.

Look at the Newman projection of the central bond as you change the conformation about this bond.

PROBLEM 2: WHAT IS THE CLOSEST APPROACH OF HYDROGENS DURING 360° ROTATION ABOUT THE CENTRAL BOND OF BUTANE. CAN YOU INCREASE THIS DISTANCE BY SIMULTANEOUS ROTATION ABOUT THE TERMINAL BONDS?

Go on to energy-minimized cyclopentane ("cyclopentane min"). Examine each of the torsional angles in Newman projection. Measure a torsional (or dihedral) angle by highlighting three successive bonds and pointing to one of them. Choose Dihedral Angles under the Analysis Menu to do Problem 3.

PROBLEM 3: FIND ALL OF THE C-C-C-C TORSIONAL ANGLES IN THE LOWEST ENERGY CONFORMATION OF CYCLOPENTANE. COMMENT ON THEIR VALUES.

[Early free version of Chem3D did not allow any energy calculations. Now you can do most of the tests below with the free Net version. I believe that looking at the tables still requires Chem3D Pro maybe the Ultra version will work.]

"Steric Energy" is the program's name for the energy due to the arrangement of atoms in space in excess of what would be expected for this constitutional isomer with ideal bond distances, angles, and torsional angles (dihedral angles). That is to say, like "correlation energy" in MO calculations, it is an estimate of error. This time it is the error that one would make by assuming that the energy can be inferred by adding up contributions from each of the bonds knowing the constitution only (having made a suitably detailed correction for the differences among bonds between different elements, and with different multiplicity).

This computational model, an example of Molecular Mechanics, assumes that contributions to the steric energy come from bond STRETCH (extension or compression from the "ideal" values, which you can see in Bond Stretching Parameters under the Tables menu); bond angle BEND (see Angle Bending Parameters under the Tables menu); STRETCH-BEND interaction (to account for change in bond bending difficulty when bonds are stretched a certain amount, values in MM2 Constants window under the Tables Menu); TORSION (see Torsional Parameters window - V1, V2, and V3 multiply cos(t), cos(2t) and cos(3t), where t is the torsional angle), and VDW, van der Waals attraction or repulsion, which is separated into interactions between atoms that are bonded to bonded atoms (1,4 VDW) and more distantly connected atoms (non-1,4 VDW) (these are derived from van der Waals radii and "epsilon" values presented in the MM2 Atom Type Parameters window). Note that additional parameters are necessary for special cases in 3- and 4-membered rings, which require more windows. Note that there is nothing quantum mechanical about this model, it is a lineal descendent of Baeyer's Strain Theory.

PROBLEM 4: WHY DO YOU THINK SO MANY TABLES OF PARAMETERS ARE NECESSARY?

For the model under consideration you can calculate the steric energy by clicking Steric Energy in the Analyze window. Try this for the Planar Cyclopentane data ("cyclopentane planar"), and note the value of the various energy components and the total. Then select Mimimize Energy in the Analyze menu and choose Minimize Energy from the resulting menu (if Minimize Energy is not highlighted in the window, you're not using an adequate computer and must try on another one). You may want to drag the "Messages" and "Model" windows apart so you can watch the model change during minimization. The Mac will adjust the structure in a number of steps to lower the energy. Note the final results and analyze what has happened. (The original structure was created by minimizing "Structural Error" rather than energy; in some versions of Chem3D this function is under Tools --> Clean Up Structure..)

Click in the Model window to activate it and rotate the model about the x-axis by 90°, then click and drag a rectangular box around one of the CH2 groups (or shift-click the two CH bonds). Then click on any one of the selected three atoms and drag it down a little to get it out of the common plane of the other four C (or H) atoms, thus breaking the molecular symmetry. Now minimize the energy again and watch the structure as its energy falls. When minimization is complete, analyze the change in the total steric energy and its components.

PROBLEM 5: COMPARE WITH YOUR COMMENTS IN QUESTION 3 ABOUT THE TORSIONAL ANGLES IN ENERGY-MINIMIZED CYCLOPENTANE. WHY IS THE TORSIONAL STRAIN NOT MINIMIZED?

Now you should learn to make your own models and minimize their energy so you can ask and answer your own questions about steric energy. When you start up Chem3D Pro you get a model window called "Untitled-1:Model" in which you can construct your own molecule.

In the little box just beneath the title bar (and to the left of the View # box) you can type the name of an atom or substructure that you want to include (for example H, Cl, CH2, C-alkane, Cyclopentyl, c-C5H9, etc. Note: these names require proper use of upper and lower case letters). If you want to see the atoms that are available, look under Elements and under Atom Types in the Tables menu. For this empirical scheme to work well, different parameters are required for the same element in different surroundings, as you can see for 14 different types of carbon in the Atom Types window. For the available preassembled substructures (like Cyclopentyl), open up Substructures under the Tables menu.

When you press return, the substructure appears in the window, with its atoms highlighted and an extra hydrogen that is not highlighted which satisfies the dangling valence of the radical substructure (if you have have not deselected the Automatically Rectify option under Building, under Model Display Settings in the View menu).

You can then modify this initial structure by selecting a particular atom and replacing it with some other group that you have specified at the top left. The replacing is done by pressing the return key. You can also use the eraser tool at the left to delete atoms, or use the single, double, or triple bond tools to create new bonds.

As you go along you can select particular bonds and adjust their conformation by double clicking in the left margin of the model window to tell how many degrees to rotate by.

As an exercise you could use the following procedure to generate cycloheptane. Start by specifying the c-C₆H₁₁ fragment (with the Rectify option on to create the 12th H). Erase a C-C bond. Use the single bond tool to attach a new carbon to one of the dangling carbons. Then simply attach that new carbon to one of the existing carbons to make the seven-membered ring. Obviously the resulting structure will be seriously strained and must be minimized in energy. You could also try simply drawing "free hand" a seven-membered ring and minimizing that structure.

Problems 1-5 are inserted within the instructions above (click for 1 2 3 4 5)

Use your new-found skills to answer the following questions. Get together to decide who will do which question and then to discuss your answers before turning them in as a group by Wednesday. Teach each other.

[Note that for the remaining problems you will need energy calculations with more than 6 non-hydrogen atoms, and thus access to Chem3D Pro or Ultra]

6) Do different individuals in your group find the same structure and energy for cycloheptane? For cyclopentane?

7) Where does the strain energy in cycloheptane come from? (compare with cyclohexane)

8) How well does Chem3D do at calculating the relative energy of variously monosubstituted cyclohexanes (e.g. axial vs. equatorial methyl, i-propyl, chloro, or iodo). See the table of A-values (Table 7.1 p. 141) in the textbook.

9) Analyze and compare the minimum-energy conformations of cis and of trans 1,3-dimethylcyclohexane.

10) What do one or two t-butyl groups do to cyclohexane?