ArgusLab Molecular Modeling Program 3.

1 (Mark Thompson)
Programm's Author: Mark Thompson,

ArgusLab 3.1 main features:

Powerful 3D interactive molecule builder:

• 3D manipulator, Fragment Library,

• Automatically Add/Hide/Delete Hydrogens,
• Periodic table tool for selecting new or modifying existing atoms,
• Automatic and manual assignment of atom hybridization and bond orders,
• Support for automatically finding rings and assigning aromatic rings,
• Automatic and manual assignment of force field atom types.

Calculation Types:

• Single-Point Energies
• Optimize Geometries
• Electronic Excitation Spectra
• Improved interface to Self Consistent Reaction Field (SCRF) Solvent Model with convenient
solvent selector to automatically set solvent parameters

Quantum Mechanics:

• Extended Huckel with parameters for the entire periodic table (supports fractional orbital
occupations),
• Semi-empirical Hamiltonians: ZINDO, MNDO, AM1, PM3,
• Restricted and Unrestricted Hartree-Fock SCF,
• ZINDO parameters stored in a user-modifiable external file,
• MNDO, AM1, PM3 parameters stored in a user-modifiable external file,
• Heats of formation for MNDO, AM1, and PM3.

Support for surfaces

• Generate Surfaces using any grid data

• Support for surfaces: simple, difference, mapped, and mapped difference.
• Generate grid files for surfaces: orbitals, electron density,electrostatic potential, and spin
density.

Support for spectroscopy, geometry optimizations, energies, and many properties:

• Ground and excited state dipole moments

• Transition moments
• Ground and excited state Mulliken and ZDO charges
 • Rotary strengths for excited states
• Calculates Charge-Equilibration charges from the Rappe' & Goddard model
• Import Gaussian cube files for surfaces.
• Read molecule structure from Gaussian .log files
• Universal Force Field (UFF) for the entire periodic table
• Build and optimize structures for the entire periodic table

• Working with Argus Lab

Argus Lab is a molecular modeling program that runs on Windows 98, NT and 2000s. Argus
Lab consist of user interface that supports OpenGL graphics display of molecule structures and
runs quantum mechanical calculations using Argus Compute Server. The Argus compute server
is constructed using Microsoft Component Object Model.

At the end of this tutorial, you will come to know

• How to build a molecule

• How to change bond length, bond angle, torsion, etc.
• How to minimize a structure
• How to calculate single point energy

Starting with Argus Lab

• Open the Argus Lab window.

• Click File -> New to open a new window. The resulting screen will look like this.
• You can build your own model using the builder tool, which is available under Tools -> Builder
Tool or using an icon in the toolbar.

• Select an atom or Ring or Amino Acid from the builder tool of your choice and right click on the
workspace.
• For building polypeptides, click on the check box Polypeptide Builder under Amino acid tab.
• To link the atoms in the workspace with the bonds, click on the icon Automatic Bond icon in the
toolbar.
• You can add Hydrogen by clicking on the Add Hydrogen icon in the toolbar.
• You can also Remove or Hide Hydrogen using the icons.
• To label the atoms, click on Label -> All Atoms.

Here is an example to construct a simple ethane molecule.

• After constructing the molecule, you can also change atoms. Right click on a particular atom
and Change atom and choose your desired atom type.

WORKING WITH BOND LENGTH AND ANGLES

• You can measure the bond length using the Display the Distance between two atoms icon in the
toolbar. Clicking on two atoms and then this icon will give you the bond length between those
atoms.
• You can also measure the bond angles and torsion angles by clicking the icons in the toolbar.
Select three atoms for bond angle and four for torsion angles.
• To change these parameters, right click on the respective values and change the values.
 MINIMIZING THE STRUCTURE

Minimizing the structure means to get the stable and lower energy conformation. Argus Lab
helps in minimizing the structure. Here are the steps to be followed

• Construct a molecule.
• We must first make sure that the atoms have proper bond length and bond angles. For this, we
must clean the geometry using the Clean Geometry icon in the toolbar. Clicking on this icon, the
molecule will be re-arranged in proper bond lengths and angles.
• Then optimize the geometry using Calculation -> Optimize geometry. The optimize geometry
dialog box will get open.

• You can work with the default values, the default option selected is MM, and you can also
change it to QM. Select the force fields. If Net charge is not 0, then you can neutralize the
charge by adding ions.
• There are two methods for minimization. You can work with either of the two.
1. Steepest Descent
2. BFGS
• While using QM, you can calculate other properties such as,
1. Dipole moment
2. Mulliken charges
3. ZDO charges
4. Wiberg bond order
• Then give start, your structure will be minimized.
• You can check the results from the View Latest Calculations Result icon.

Screenshot for MM:

Screenshot for QM- Mulliken charges:

SINGLE POINT ENERGY CALCULATION

Single point energy is the potential energy of the molecule for the particular arrangement of the
atoms in the molecule. This calculates the wave function and charge density. To calculate the
single point energy, follow these steps

• Construct the molecule and give clean geometry.

• Under Calculation, give Energy.
• Similar to minimization, various options are available for single point energy calculation under
QM and MM.
 VIEWING SOLVENT ACCESSIBLE SURFACE

The path traced by the centre of the probe around the molecule is called as solvent accessible
surface. We can view this surface using Argus Lab.

• Click Surfaces
• Solvent accessible surface.
Exercise on modeling, using Arguslab

This exercise is intended primarily to be used in a three-hour drylab session, with active teaching
by demonstrators. After that, it should be very useful for private study as a revision
aid. Arguslab is available directly on Campus cluster PCs.

Arguslab offers quite good on-screen molecule-building facilities, with a moderate library of
useful molecules. The viewer is mouse-controlled quite similarly to Rasmol/Chime. Arguslab
can do geometry optimisations using the UFF force field. This covers all elements of the
Periodic Table because it is not restricted to known atom types in its parameterisation, though it
does use some common ones. The resulting energies are distinctly different from those obtained
using some of the more conventional force fields, and wherever possible one needs to reoptimise
at a higher level. For this, Arguslab offers geometry optimisation using the MNDO, AM1 or
PM3 semiempirical levels, as well as single point calculations using these, though the range of
elements covered is much less. There are also single point semiempirical calculations using
Extended Huckel (for a bigger element coverage) or ZINDO (for excited states for UV/visible
absorption prediction). Version 3.1 of Arguslab has good facilities for calculating electron
density or orbital surfaces at the semiempirical levels, and displaying them. It can also map
another property, e.g. electrostatic potential, onto a surface, similarly to the display facilities of
Chime (see Notes: An electronic model of methyl thiirane). This will be the subject of a further
document: Drylab: Calculating Surfaces using Arguslab

File storage

Arguslab writes its own format of molecule file, .agl, but it can also write .xyz, .mol, and .pdb
files for input to other programs.

Starting and Stopping in Arguslab

• To start work, you should either press the 'New' button (top left) to get a new molecule
screen, or you should press the 'Open' button to read in a molecule which you have saved
previously in the your Argus directory.
• In Arguslab, you need to save your molecule with whatever name you want before doing
a geometry optimisation as well as afterwards. This is so that all the ancillary files will
have the right names. If you forget to change the file name before modifying a molecule,
files will be saved automatically with the name you used previously, possibly destroying
data which you wanted to keep.
• It is best not to maximise the molecule window, because then its title bar will display the
name by which you are currently saving the files. Just drag its bottom right corner so that
it fills most of the Arguslab worktop.

• To stop using Arguslab, click File Exit. You will find that if you have molecule windows
open, this will just close one of these. You need to do it repeatedly to close all the
windows (if you have several open) and then stop the program.
Assignment 1: Conformations of cyclohexane and methylcyclohexane

Chair cyclohexane

• Press 'New' button (top left) to get a new molecule screen

• Read chair cyclohexane from the fragment library by pressing the 'Add fragment' button
(pencil pointing to benzene ring), Fragment Library, ..., then when you have found the
right file, right click in the window
• Click the select button (diagonal yellow arrow) then click anywhere on the black
background to get rid of the manipulator frame
• Save in your Argus directory as cc6_c_uff
o BWT advice: keep names to 8 characters or less, so they will be compatible with
any programs. cc6 is the petroleum industry shorthand for cyclohexane: any
ideas, which help you to make up file names self-evident to you, are useful. The
middle c stands for chair conformation.
o Include the method which will produce the files in the file name: here the uff
ending says that you are about to do a UFF geometry optimisation.
• On the Calculation menu, set up to do a UFF geometry optimisation. OK the dialogue
box, then do the calculation by pressing the calculate button (Bunsen burner?)
• Save (this will overwrite your previous .agl file with the optimised version)
• Read the output using the list output button (looks like a sheet with writing on it) and
note down the energy onto paper (a small positive number of Hartree units to high
precision: you need all the digits!) from the end of the output file. This is the UFF
energy of chair cyclohexane. [If you were doing this in real research, you might have a
Notepad window open (available from the PC desktop) and copy and paste the numbers
with suitable annotations, so as to avoid the possibility of copying errors, which are only
too easy with these tedious long numbers. You could then save from Notepad to a text
file afterwards.] Close the output viewing window
• Save as cc6_c_pm3 ready to do a PM3 optimisation
• Set up Calculation, Optimise geometry, to do PM3. OK Bunsen
o You will see this goes more slowly than the force field method, but is still very
fast for this size of molecule
• Save
• List the output as before: you can see that Arguslab tells you a lot about the molecule
before optimisation, but nothing about it afterwards. It appears that you are intended to
run a single point calculation after the geometry optimisation to obtain the properties,
including the final energy.
• Set this up by Calculation, Energy: notice that you have to click PM3 again: it does not
remember from last time. Bunsen
• Now you can list the new (single point) output, and note down the energy in Hartrees
(negative: this is electronic energy) from the last page of the output

Twist boat cyclohexane

• Open your model cc6_c_uff

• Save as cc6_tb_uff
• Remove hydrogens with the Delete Hydrogens button (H with an eraser)
• View as sticks (View, Display settings, Cylinder Normal)
• Turn the molecule so that you are looking at the ring approximately edge-ways on, so that
you can see it as a chair, with the head atom on the left and the foot atom on the right,
and so that you can see all the atoms separately
o The button with an arrow with a red ring around its shaft switches left drag to
rotate the molecule around the z axis
o The intersecting elipses button switches back to x or y rotate
• In select mode, click on the atom at the foot of the chair. It should highlight
yellow. Then press the delete button on the keyboard, to remove that carbon. (In this
program, for this molecule, it is easiest to remove it altogether, rather than breaking just
one ring bond and trying to rotate singly attached carbon to the right position for boat.)
• Change to Add atoms mode (button to right of select mode button)
• Click on the 4-coordinate C button
• Make sure the Automatic bond button (red bond joining blue atoms) is not lit
o If Automatic bond mode is not on, you will not accidently join atoms together by
clicking on them
o You can intentionally make a bond between two atoms by holding down the Shift
key while clicking the two atoms in succession
• With the left mouse button, select one of the currently terminal carbon atoms
• Place the mouse cursor as carefully as possible where you judge the missing carbon of
the boat conformation should be, hold down the shift key, and right click to put a carbon
there
• Hold down shift, and click on the other terminal carbon atom, so as to close the ring
• Change to Select mode
• Press the add hydrogens button (H)
• Save
• To do a UFF geometry optimisation you could press the pincers button (for pulling things
roughly into shape?) but you might as well use Calculation Optimize geometry to set it
up, so that you can change the maximum number of steps from 100 to 200 before you
start. Otherwise you may find the optimisation routine stops before it finds the minimum
(in which case you can press Bunsen to continue with another bout)
• Save
• View the result by rotating the molecule
o You should not have landed back in the chair form. If you have, you did not get
your built geometry close enough to that of the required conformer, and you need
to do this experiment again
o You will not have found a boat conformer (C2v symmetry) because this is not
stable for this molecule: it is a saddle point between two twist-boat enantiomers
o You should have found one of these twist-boat conformers. As they are of equal
energy by symmetry, it does not matter for present purposes which one you have
found.
• Find the UFF energy as for the chair conformer, then do a PM3 geometry optimisation
(file name cc6_tb_pm3), as before, and find the PM3 energy of the result.
Energy comparison of the cyclohexane conformers

• Remembering that one gives positive energies and the other negative, you should have
found that the UFF and PM3 methods have given the same order of stabilities for the two
conformers. Which is the more stable?
• By careful use of hand calculator, find the energy of the less stable conformer relative to
the energy of the more stable, for each method, converting the energies to kJ mol-1. To
convert from Hartrees to J mol-1, multiply by 2625515. If you have spare storage in your
calculator, this is a useful number to store for present purposes
• Convert each of the two energy differences to an equilibrium constant, using the
Boltzman distribution:
K = exp (-∆E / RT )
Remember that ∆E has to be in J mol-1, not kJ mol-1. Use T = 294 K. R is the gas
constant, 8.3145 J K-1 mol-1 (another good constant to store!)
• According to Goodman, the experimental energy difference is 23 kJ mol-1, which on the
present basis (ignoring entropy), would convert to K = [more stable]/[less stable] = 12198
o What is your assessment of the UFF and PM3 methods for finding energies for
this molecule?

Symmetry of twist-boat cyclohexane

• To know where you are in modelling methylcyclohexane conformers, you need to find
the symmetry elements in twist-boat cyclohexane. The molecule has D2 symmetry,
which means that it has (only) three mutually perpendicular C2 axes: one threading the
centre of the ring, one through two opposite carbons, and one through the middles of two
opposite bonds
• Display sticks, and rotate the model so that you look down each of these axes in turn, and
convince yourself that they are indeed C2 axes. Leave the model so that you are looking
down the axis which passes through the bonds
• Because there are no improper axes (including planes or centres of inversion) in D2, the
molecule is chiral, i.e. this is one enantiomer
o Turn the model carefully about the x axis (i.e. downward left drag) until you are
looking down the axis which threads the ring.
o The top two carbons on your screen should now come towards you from back left
to front right, or vice-versa. If you turn the ring through 180° in either direction,
you always get back to the same sense. The other enantiomer has the bond going
the other way

The five conformers of methylcyclohexane

In this part of the exercise, you use the models of the two conformers of cyclohexane, which you
have saved, to create models of the five conformers of methylcyclohexane. For each, do a
preliminary UFF optimisation, then a PM3 geometry optimisation, then a PM3 single point
calculation to get relative energies. Write these down, and calculate energies relative to that of
the most stable of the five conformers.
• Be very careful to use Save as.. to save each model with a different name, before you
start to construct it from the cyclohexane model, otherwise you are very likely to
overwrite the cyclohexane model by accident, which will be a nuisance because you will
need to use it again for constructing the next conformer of methylcyclohexane
• Start with twist boat cyclohexane, while its symmetry is fresh in your mind
• Look down the axis which passes through carbon atoms
o The two H atoms on the near carbon are related by the symmetry axis, so
replacing either by CH3 will give the same conformer
o The two H atoms on the distant carbon are related to the first two by the C2 axis
which passes through bonds, so replacing any of these four H's will give the same
conformer
o Possible filename: mecc6tbonuff (difficult to keep this short! the 'on' means
attached to C on a C2 axis)
• Look down the axis which passes through the bonds
o On each C nearest to the axis, there are two kinds of H: one approximately
parallel to the axis, and one approximately perpendicular to it. These will give
two different conformers of methylcyclohexane
o Possible filenames: mecc6tbparuff and mecc6tbperpuff
• To substitute the methyl group, in select mode, right click on the H to be replaced. On
the drop-down menu which results, left click on Change atom. Select C sp3
• Add hydrogens to the new carbon, using the Add H button
• Save, then do UFF optimisation. Make sure the job has converged, rather than reaching
the number of cycles limit. Save and go on to the PM3 optimisation, etc.
• When you have done the three twist boat conformers, go on to the chair conformer of
cyclohexane
• This has D3d symmetry, so it has a S6 axis threading the ring
• Look down this S6 axis, i.e. so that you see the ring as a regular hexagon
o On every carbon there is a hydrogen pointing outwards, i.e. not directly towards
you
o These H's are called 'equatorial' and are related by the S6 axis, so they are all
equivalent
o Possible filename for the methyl derivative: mecc6cequuff
o In the same view, there are three H atoms pointing directly towards you, parallel
to the S6 axis
o There are another three, related to these by the S6 axis, pointing directly away
from you, so you should not be able to see them
o These six H's are called 'axial'
o Possible filename for the methyl derivative: mecc6caxuff

• When you have all five conformers, see which has the lowest energy
o Calculate the PM3 energy of each of the others relative to it, in kJ mol-1
o According to Goodman, the MM2 relative energies are:
0, 7.44, 24.61, 26.68, and 30.02 kJ mol-1
o How do the differences between these compare with yours? It is not completely
clear from his pictures, which is which. When you have the book to hand, try
comparing it with your notes from these exercises.
Assignment 2: N,N'-Diadamantyl-imidazol-2-ylidene

First you have to pick a nice molecule that caught your interest. I'll stick with ligands. N,N'-
Diadamantyl-imidazol-2-ylidene looks kind of cool and I am wondering if modeling
carbenes works well. To start out you can do the same things that I am doing with any
smaller molecule.

For drawing the basic structure, a typical chemical structure drawing program works best. I
like ChemSketch. Other people like ISIS/draw. In there you draw the structure. In my case it
looks something like this (the c-hexane rings are 3D-rotated):

As a next step you should add the hydrogens in ChemSketch (this works better than adding
them in ArgusLab). For quick qualitative results ChemSketch has an optimisation function.

For molecular modeling with more options you can use ArgusLab. To do that you have to
export the structure as a molecule file (.mol, .pdb, or .xyz) and open this file in ArgusLab.

Next you should go for "clean hybridisation" (Ctrl+B). The ring becomes aromatic. After
that you set up a geometry optimisation (benzene ring button). For a first optimisation
molecular mechanics work best. UFF (universal force field) works, AMBER doesn't for some
reason. This is the molecule after UFF.
As a next step ArgusLab offers semiempirical QM for structure optimisation. AM1 (Austin
model 1) and PM3 (parametrised method 3) are supposed to be the best ones. In this case I
used AM1. If you use a molecule this size optimisation takes quite a while. But that is ok
because ArgusLab perfectly works in the background.

At first glance the optimisation doesn't make much of a difference. In the following two
pictures it can be seen that bondlengths did change a little bit. An interesting fact is that the
second structure which was optimised with QM works better with the resonance structures.
The bond in the imidazole that is a single bond in every resonance structure really is longer
than the other ones.