recently as 15 years ago, using computers to model reactions, calculate
reaction energies and steric parameters, and calculate, with great
visualizations, the energetic minima for a structure, was mainly the
area of physical chemists and a few strange organic chemists with a
weird attraction for mathematics. During the intervening years,
though, many software packages have become available - from free to
quite expensive and sophisticated (but still running on a PC) - and any
synthetic or medicinal chemist who still doesn't utilize these tools is
seriously behind the times.
This short tutorial is designed to provide an introduction to
computational chemistry as applied to organic reactions, in two totally
different environments. Part 1 deals with PC-based calculations,
where you use a program installed on a PC to execute and display the
results of molecular calculations. Part 2 is an introduction to
server-based calculations, where you access a site where everything
is done on the site's computers; these services are generally free,
which are the only ones that will be discussed.
are a number of commercial software packages that are used for this
purpose; probably the best known are Spartan® Chem3D.
Spartan, supplied on many CDs that accompany organic chemistry texts,
is a standard energy minimization and energy calculation package;
Chem3D, however, is capable of much more diverse calculations,
algorithms, visualizations, and file formats supported. Thus, the
intention of Part 1 is to familiarize you a little with CambridgeSoft's
great Chem3D-Ultra program. Chem3D does things that, until very
recently, were thought to require the power of a mainframe; the great
increase in both hard disk size/speed and RAM, combined with elegant
algorithms reducing the complexity of the calculations, has enabled
virtually any required calculations, including ab initio (totally quantum mechanical)
programs. Depending on the complexity of the molecule being
studied, some calculations can take some time, but I've yet to run one
that required more than about 15min.
With Chem3D, the structure is best drawn
with a chemical drawing program, then copied/pasted into the modeling
program. The best free application is called ISIS Draw, by ACD
Labs, Inc. To get yours, just click the logo to the right.
Requires a (free) short registration, and they won't drown you with
spam or sell your address to a gazillion other vendors.
Look at ISIS/Draw
It's fairly self-explanatory, but a few comments
will save you some time. First, let's take a look
tool bars across the top. The shapes across the top are probably the
you'll need. Down the left column is a series of commands, but there's
than that. Any command with a small arrow in the lower right (the great
majority) is just one of a series, which can be visualized by
right-clicking on the icon. You'll be amazed at how much was crowded
into such a small, *free* program! (By the way, the icon at the bottom
of the list involves "AutoNom", ACD's nomenclature program. Just select
your structure (with the topmost icon) and click AutoNom, and within 3
seconds, you'll have the IUPAC name!
Pasting Into Chem3D following be a Quick Minimization
Once you're happy with your structure, just select
it and copy it to the clipboard, then go to Chem3D and paste it in.
Usually, it doesn't look too good at first, so it's common to do a
quick conformational minimization using the molecular mechanics
protocol. Take a look at the Chem3D
command bars. In the middle of the bottom row is an icon called MM2,
which stands for molecular mechanics, and is a shortcut to an energy
minimum. MM is the fastest of the computations, and is a great way to
start. As it's calculating, look at the "output" area (across the
bottom of the screen) - you can see the energy falling as the model
moves around, seeking the structure with the lowest energy.
Now that you've got
a decent-looking model, you can do whatever it is you came to do. To
get a better quality minimization, you can go to the "Calculations"
button, and choose from one of the other available methods, the most
typical of which are MOPAC (semi-empirical, i.e., a mixture
of MM and quantum mechanics), and GAMESS (totally ab initio,
or quantum mechanical).
A Hidden Hint
About Calculating Huckel Charges and Surfaces
The best way to get to know the program is just to
play around with it a lot, and use the great help files (F1). Some
things are not as well documented as they could be - for instance, if
you wanted to calculate Huckel charges and/or create Huckel surfaces,
you'd go to the "Surfaces" button, right? Wrong. First you go to
Calculations, where one of the pull-down options is "extended Huckel",
from which you can choose "charges" or "surfaces". You have to
calculate the parameters before you can show the result, see? It may be
documented somewhere, but it's escaped me so far.
The navigation buttons: The
bottom row begins
with several icons to govern what your mouse does. The arrow is for
selecting certain structures or atoms. The hand is for moving objects,
which needn't be selected - just get the hand near the structure. The
curved arrow, next, is the most common mode, which allows rotation of
the structure through all three dimensions simultaneously. The Up/Down
arrows make an object larger or smaller. The four-way arrow moves
individual pieces, like atoms, bonds, etc.
The upper row of icons is self-evident until you get to the purple
thermometer (it's actually a double bond, but it had me fooled..). From
here, you select the model type (lines, wireframe, ball&stick,
space-filling). After the background color icon, you can choose what
type of stereo you want - either the silly-looking red/blue goggles, or
the useless polarity filter. Then come two icons for 3D effects -
"perspective" and "depth fading". The former makes distant things
smaller than nearer ones; the latter dulls the light on more distant
things. The two can be combined to give a look that's unusually silly.
Then come two icons for showing two axes, two for atom labels or
numbers, and finally you can switch to full-screen mode or make the
The Output of Energy (and other) Calculations
calculations are done in the "Output" area right below the Chem3D
window (if you can't see it, it may be minimized, but it's definitely
there). Fortunately, it never discards any calculations until you leave
the program; by scrolling up you can retrieve any calculation done
during the whole session - even those leading to lousy results.
Structures as either Vector or Image Files
Chem3D's strengths is the incredible number of file formats it can both
read and write. I've never actually counted them, but there must be 50
formats - from common visualization formats like .pdb (Protein Data
Bank), .mol (MDL-generated images), and .cdx (ChemDraw); to more
obscure ones like .int (internal coordinates), .xyz (Tinker MM3 Input),
and .rdl (Rosdal). It can also save the actual images, in all the usual
formats (gif, jpg, bmp, png, tif). If you want to prepare an annotated
image (add writing or something else to it), the best thing is to save
the image in png format (it's the most general), and then use a
graphics program (FireWorks, PhotoShop, Paint, etc.) to add the text.
installed on most of
the computers in the computer lab, as well as the lab computer. I know
there's a certain energy of activation when deciding to learn a new
thing, but you'll have this program down in no time, and find yourself
playing with it for hours, so - about that Eact - get over it and have