Time is money. Research is expensive. You are faced with the alternatives of setting up a laboratory (or utilizing an expensive laboratory already set up) to discover new…
The process of discovery is often unpredictable. Even the very best laid plans and the best work force are often faced with problems for which there is no known solution. Occasionally, it is possible to follow leads (not covered in patents belonging to others) and devise new solutions to your particular problems. In other cases it is not.
Among the current paradigms adopted in many industries is that of modeling compounds and systems that might lead to appropriate solutions to the problems noted above. For example, in the health/welfare industry, what pesticide is best used to spray for mosquitoes or what medication is best to fight asthma or how do we find a new drug for AIDS. Alternatively, in the transportation industry, what mixture of combustible materials is best (cheapest) used for propelling automobiles equipped with internal combustion engines or is it possible to design new and better batteries.
In many such cases, information about the system at hand will drive research. Usually, it is in the best interests to have an idea about the direction in which to go before heading into the laboratory to try the idea.
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An Introduction to Molecular Modeling |
Computational methods are now available which allow the simulation of the structures of molecules and prediction of some of their properties. In many cases, where measurements have been made subsequent to the predictions, these computational methods have proven their worth.
The broad and growing number of such methods has derived strength from the speed at which new computer hardware and software is introduced and developed. Indeed, it is now clear that quality calculations can be carried out on widely available desk-top equipment such as that available to us in this course.
Broadly, the current tools can be described as [a] ab initio (first principles) methods, [b] semi-empirical methods, and [c] empirical methods. Ab initio type calculations require some constants (such as the speed of light, etc.) and the use of quantum mechanics (the application of sets of equations that successfully describe the motion of electrons in atoms) alone. Generally, ab initio calculations are time consuming and applicable to only the smallest molecular systems. Semi-empirical methods use some experimental data to approach approximate solutions to the more exact quantum mechanical equations and, depending upon the desired outcome and the particular approximations (their level), can be valuable for comparing properties of sets of molecules. Empirical methods, which have become very popular, utilize; (a) predefined atom "types" such as the "different" carbons resulting from known atomic locations in molecules (from, e.g., x-ray crystallography of related systems) and the connectivity and bond angles resulting from geometric measurements; (b) equations derived from classical physics that predict interactions among nuclei as if they were "hard spheres" and; (c) sets of parameters to fit the equations and atom types to experimental data.
With regard to the latter, while it might seem that such empiricism would lead to results of limited utility, the methods have established their value (as very good approximations) by their successes. Among the more successful empirical methods is the Molecular Mechanics (MM) force field whose creation and establishment is due largely to the efforts of Professor Lou Allinger (Allinger, N.L., Professor of Chemistry, University of Georgia) and coworkers. The MM method will be used here with the ALCHEMY III program (Tripos Software Inc.).
Additional material can be found at
http://www.ch.ic.ac.uk/local/organic/mod/.
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Using the PC to run ALCHEMY III |
Alchemy III
(1) Using the mouse, direct the pointer to the box and, with the head of the arrow pointing at ALCHEMY III, click the LEFT mouse button twice in rapid succession. On the first click, the color of the Tripos Desktop header will change and, on the second click, the figure of the "hour glass" will appear while the program loads.
(2) Successful loading of the program results in the Windows screen being replaced by the Alchemy III screen. The Alchemy III screen is shown below.
A picture of the ALCHEMY III screen. NOTE that the region across the top containing the words File, Edit, Display, Build, Atoms, Help is called the "MENU BAR".
Note that the screen is divided into four (4) major areas
(a) The Auxiliary window at the upper right,
(b) The Gadget Box at the lower right,
(c) The Messages windows at the lower left. and
(d) The main window, labelled ALCHEMY III, holding the menu bar...
THE MENU BAR
ALCHEMY III works through interaction of the information contained in the MENU BAR and the various screens. The MENU BAR is accessed with the mouse. When the arrow controlled by the mouse is pointed at any of the items in the MENU BAR and the left mouse button is clicked, that item becomes active, and a pull-down menu appears. The choices in the pull-down menu can be accessed by pointing the mouse to the choice and clicking on it or by using the arrows at the lower right of the computer keyboard to reach the choice.
Exercise 1. Point the arrow at each of the items in the MENU BAR
File Edit Display Build Atoms Help
Exercise 2. Point the arrow to the MENU BAR item labelled File. Using either the mouse or the down arrow move the highlighted bar to the last item, labelled Quit.
The function of this item is to enable you to leave ALCHEMY. This Exercise will cause you to quit the ALCHEMY program. You should then begin again from wherever the computer leaves you and return again to this point.
NOTE...It is always most important to learn how to get out of any program. Try it!
Click the left most mouse button while pointing to the word Quit and exit ALCHEMY. Restart the Program and get to the beginning of Exercise 2. Do not (unless you have had trouble) repeat Exercise 2. However, you will need to Quit the program at the end of the period.
EXCEPT FOR THE ITEM Quit you will not be using any of the other commands under the File menu at this stage. Later you may use others.
The Edit menu is the second item (from the left) in the MENU BAR. Most of the items in the Edit menu are not implemented in this version of ALCHEMY III and thus are not active when you go to Edit.
The Help menu is the last item (from the left) in the MENU BAR. The Help menu has only two items under that heading. Therefore, if you click the left most mouse button while the arrow is on Help you will find the Help Index and information About ALCHEMY III which gives the version number of the program. The Help Index contains information specific to ALCHEMY III and will not help you with general computer questions. In the Help Index you will find help on what the help menu does and how to use it as well as specific information about each of the commands in other portions of the MENU BAR. You should feel free to explore the Help menu at your leisure. TO LEAVE THE HELP INDEX, point the mouse to the word "FILE" at the left most part of the "Help" MENU BAR, depress the left most mouse button, and move down the pulldown menu to Quit. Highlight ON Quit and you will be returned to the main program.
Today you will be working with the center three headings in the MENU BAR.
Immediately to the left of the Help item in the MENU BAR, you will find the heading for the Atoms menu.
Point to the Atoms heading of the MENU BAR and "click" the left mouse button. Notice that an entire menu of abbreviations appears. These are not only for certain elements, but they are also for atoms in various oxidation states. In the left most column, fourth from the bottom, you will see the item "C3". It is immediately below "C2". Point to the item "C3" with the mouse arrow and click on the left mouse button.
Notice that the menu disappears and that the Auxiliary screen (upper right) contains some object.
The object contained in the Auxiliary window corresponds to a carbon atom with four identically spaced ligands. It is called an sp3 hybridized carbon.
Point the mouse arrow into the Main Screen (or window) of ALCHEMY III and click the left mouse button. Note that the fragment now has moved into the Main Screen (and a copy remains in the Auxiliary window too).
A carbon atom bearing four hydrogens (CH4) is called "methane". In order to "build" methane from the fragment seen in the Main window, you must add hydrogens to each of the four "open" ligand positions on the carbon atom. To do that...
Point the mouse arrow to the MENU BAR and click (the left mouse button) on the item labelled "Build". When the menu appears, move to the first item, labelled "Add" and, holding the left mouse button down, slide the mouse to the right (in the direction of the arrow after "Add") until the first item "Hydrogens" is highlighted. THEN RELEASE THE MOUSE BUTTON.
Notice that the "unfilled" valences around the sp3 hybridized carbon are now "filled". That is, the color at the end of each line has changed to blue.
This is a representation of methane (CH4).
The rest of this indroduction involves manipulating methane using the "Gadget Box" and the "Display" option of the MENU BAR.
Point the arrow of the mouse to the item in the MENU BAR labelled Display and click the left mouse button.
There are four different Display modes. The first (and default) mode is the simple line (wire-frame or stick) drawing which already exists on the screen. The other three, Space Fill, Ball and Stick, and Cylinders may be seen by pointing to any one of these items and clicking the left mouse button. To return to the line drawing simply click again on which ever of the three display modes bears a check mark (to de-select it).
Exercise 3. Switch between the various display modes available and then back to the line drawing.
It is now time to explore the Gadget Box.
The tools in the Gadget Box allow you to control the movement of the object(s) in the Main Screen. The movement is controlled by using the mouse (and the left mouse button) and the X,Y Grid, the Z slider, and the 90o flip buttons. In addition, the size of the object(s) in the Main Screen are controlled by the scale slider (S).
You should explore the use of the gadget box with methane (CH4) until you understand what is accomplished with the various tools in it.
Exercise 4. Explore the tools in the gadget box and the various display modes available together. Remember that when the "hour glass" appears, it means that the operation is being carried out and that you should WAIT.
NOTICE how long each function in the Gadget Box takes when any but the line drawing (wire-frame model) is displayed.
Exercise for CIS 55
When hydrocarbons (compounds of hydrogen and carbon) are burned in the presence of an excess of oxygen the products are carbon dioxide and water, i.e.,
hydrocarbon + O2 ® CO2 + H2O + heat.
The amount of carbon dioxide and water produced is a function of the number of carbons and hydrogens with which one begins. However, the amount of heat produced is a function of the initial "heat content" (called the "enthalpy" and abbreviated as "D H") of the hydrocarbon. The enthalpy, in turn, is a function of a number of molecular constraints which include; (1) the molecular weight of the hydrocarbon, and; (2) the arrangement of atoms within the hydrocarbon.
Since each carbon (in hydrocarbons) is required to coordinate (form bonds) to four other nuclei (carbon or hydrogen) and each hydrogen is required to coordinate (bond) to only one other nucleus, it follows that each hydrogen is bonded to only one carbon but each carbon has three other bonds…
The next exercise today will be to create networks of such bonded carbon and hydrogen atoms. The single criterion to be applied is that there must be eight (8) carbon atoms in each structure drawn. If there are eight (8) carbon atoms then the structures produced will be constitutional isomers (from the Greek "isos" + "meros" meaning "of the same parts") of the hydrocarbon family of "octanes". The drawings must then be (1) minimized and the corresponding energy recorded, (2) the drawings matched with those shown below and the appropriate names (given with the drawings) assigned, and (3) the relative enthalpies obtained from the NIST database. A comparison of relative energies obtained from the minimizer in Alchemy III with the actual experimental enthalpies (from the NIST database at http://webbook.nist.gov/) should be made. What conclusion do you draw?
