Building Structures and Habits

Building a molecule...............................................................1-2ab

Building ions.........................................................................2

Building radicals....................................................................2

Changing Chirality.................................................................2

Changing from E-Z................................................................2

Changing from chair to boat...................................................3

Building complicated structures..............................................3

Build small chiral pieces..............................................3

Assemble small units into macrosystems......................3-4

Molecular Mechanics

Theory....................................................................................4

Components............................................................................5

Force field options...................................................................5-6

Default settings........................................................................6-7

Further readings or references....................................................7

Illustration................................................................................7

Semi-Empirical

Theory.....................................................................................8

Background.............................................................................8

Simplifications.........................................................................8

Force fields..............................................................................8-10

Options...................................................................................10-11

Log File..................................................................................11

When to use............................................................................11

Illustration...............................................................................11

Further readings or references..................................................12

AbInitio

Theory.....................................................................................12

Calculations.............................................................................12

Molecular Dynamics.........................................................................12

Theory.....................................................................................12

Information..............................................................................13

Running and Parameters...........................................................13-14

Orbitals and Contour Plots...............................................................14

UV/Vis Spectra...................................................................................15-16

IR Spectra

Theory......................................................................................16

Calculations..............................................................................16-17

Using Excel Macro.............................................................................17

Trouble Shooting................................................................................18-19
 
 

To build a molecule

Suggestion: To get an in-depth overview of building in Hyperchem see Lessons 1-8 in Getting Started Manual

I. Double Click on the upper left icon (draw icon)

I. Go to the display menu.

Building an ion

· First, go to the Build menu and make sure the allow ions command has been selected.

· Next, draw the compound of interest in the same way you would draw any other compound, but include all hydrogens in the structure.

· Select whichever atom you wish to make the ionic atom using the select icon, and set the charge using the Set charge command under the Build menu.

· Go to the Build menu. If add H and model build is an option, click on explicit hydrogens.

· Click on model build to finish your molecule.

To build a radical

· Build in the same manner as an ion, but do not set any atom charges.

To change the chirality of a molecule

· Make sure Multiple Selections is on

· Select the stereocenter and the adjacent atoms of the second and third priority groups

· Click on Name Selection from the Select menu and select PLANE

·Deselect the entire workspace

· Now select all of the atoms associated with the first and fourth priority groups

· On the Edit menu, choose Reflect

· The chirality should be changed

To change an E-Z isomer

· Make sure Multiple Selections is on

· Select the atoms in the double bond and an atom adjacent to each side

· On the Edit menu, select Set Bond Torsion

· If the angle reads 0, set it to 180, if it is 180, set to 0

· The isomer should be changed

To change from chair to boat conformations

· See pp. 125-128 of the GS Manual

To build a more complicated structure

One of the most difficult thing to do on Hyperchem is assign proper symmetry to chiral centers. The best way to build a more complicated structure is to divide it into smaller, pre-formed pieces. This way, one can easily determine if the right stereochemistry is present in these smaller pieces before putting them together to make a larger piece.

Building small, chiral pieces

In establishing chiral centers, one of the best things to do is simply put in one carbon atom, add H and model build, and then replace the H’s with other substituents. This way, you can put the substituents in either an R or S manner, and the chirality is immediately present. In order to ensure that you have the correct chirality, choose chirality from the Label menu to illustrate whether the chiral center is R or S. Add H and model build each of these subunits separately. Once you get something to work, save it immediately. That way, if the next step goes awry, there is a place to start.

ex. Make a molecule of methane. Replace 3 H’s with a Cl, a OH, and a CN. Make the R and the S isomer.

Assembling small subunits onto macrosystems

One problem with Hyperchem is trying to get structures to look accurate. When assembling a large structure from smaller pieces, it is best to try and put the pieces together so they look somewhat like what you expect.

· first, open one of the small pieces you have saved.

· next, go to the merge command from the file menu, and use it to open another piece.

· go to the select menu, and click on molecules. Then select one of the pieces using the select icon, and drag it towards the other piece using the fifth icon (drag icon) and the right mouse button.

· Note: position this piece in a manner such that when connected, the two pieces resemble your preconceived idea of the molecule’s shape.

· now, join the two pieces together. DO NOT add H and model build, as this will likely cause your molecule to do some unpleasant things.

· connect all your remaining pieces in this manner, and then minimize the structure.

When you do save Hyperchem structures, you may not necessarily be saving all of the information you have entered into the molecule. For example, if you set the torsion angle of a certain molecule, upon saving it, you will lose the value you set. Be sure to keep a careful record of all changes you make to your molecules, so that you can re-enter these values if necessary. Also, Hyperchem does not generally reset its parameters to defaults. In all uses of Hyperchem, it is important to make sure that the program is set up EXACTLY the way you want it. Do not assume that because it was set up right one time it will be set up that same way the next time.
 
 

I. Theory

· Bond angles

· Torsion angles

· Nonbonded Interactions

· van der Waals forces

· electrostatic interactions

· hydrogen bonds

· Optimization of your system before a semi-empirical calculation

· Comparison to literature MM2 values

In these calculations, the forces on atoms are functions of atomic position.. A molecule is described as a collection of atoms that interact with each other by simple analytical functions. This description is called a force field, many of which arise as a harmonic oscillator using Hooke’s law. Ultimately, molecular mechanics is used to describe the physical properties of the molecules

The potential energy of a molecular system in a force filed is the sum of individual components of the potential. Molecular mechanics methods calculations cannot describe bond formation and bond breakage, or systems in which electronic delocalization or molecular orbital interactions occur.
 
 

II. Components

The molecular mechanics force field dialogue box can be obtained under the setup menu. There are four different methods that can be chosen:

Choose a Force field that has been paramaterized on a system similar to the one that you are using.

· MM+

This force field was developed for organic molecules. This supplements MM2 by providing additional parameters(force constants) using two alternative schemes. MM+, for this reason can handle a wide variety of molecules. It also provides cutoffs for calculating non-bonded electrons. Hyperchem chooses this option as the default option.

· AMBER

This method was developed for proteins and nucleic acids

Can be used as an all-atom option or united option(treats certain groups as one atom).

· BIO +

Developed for biological macromolecules. Can be used as an all-atom option or united option(treats certain groups as one atom).

· OPLS

Developed, like AMBER, for proteins and nucleic acids. Unlike AMBER, it treats more accurately non-bonded interactions. This option only provides a united-atom simulation.

III. MM+ Force Field Options

The MM+ force field option dialogue box can be obtained by clicking options in the Molecular Mechanics Dialogue box. Two options are presented:

· Electrostatics:

You can choose between:

· Bond Dipoles- Uses bond dipoles to calculate non bonded electrostatic interactions.

· Atomic Charges- Uses partial atomic charges to calculate nonbonded electrostatic interactions.

· Cutoffs:

You can choose between:

· None- Calculates all nonbonded interactions

· Switched- Smoothing function, applied from the inner radius to the outer radius, gradually reduces nonbonded interactions to zero.

· Shifted- Smoothing function, applied over the whole nonbonded distance from zero to the outer radius, gradually reduces nonbonded interactions to zero.

· Outer Radius- This is the minimum distance at which nonbonded interactions are set to zero(switched and shifted).

· Inner Radius- This is the maximum interatomic distance for full nonbonded interactions.

IV. Default Settings

Although Hyperchem does not reset the default settings, it may be useful to know the defaults.

MM+

· Electrostatic- Bond dipoles

· Cutoffs- None

Amber

· Dielectric (epsilon)- constant

· Scale Factors- 1.0

· 1-4 Scale factors

· Electrostatic- 0.5

· van der Waals- 0.5

· Cutoffs- none

BIO+

· Dielectric (epsilon)- constant

· Scale Factors- 1.0

· 1-4 Scale factors

· Electrostatic- 1.0

· van der Waals- 1.0

· Cutoffs- none
 
 
 
 

OPLS

· Dielectric (epsilon)- constant

· Scale Factors- 1.0

· 1-4 Scale factors

· Electrostatic- 0.5

· van der Waals- 0.125

· Cutoffs- none

5. Further Readings or References

· Kolossvary, I and Guida, W.C. J. Am. Chem. Soc., 1993, 115, 2107.

· Allinger, N.L. J. Am. Chem. Soc., 1977, 99, 8127.

· Engler, E. M.; et al. J. Am. Chem. Soc., 1973, 95, 8005.

· Kollman, P. A.; J. Am. Chem. Soc., 1985, 107, 2212.

Illustration:

Consider the Structure Naphthalene

Construct the system shown above in Hyperchem and invoke the Model Builder and Add Hydrogens. Once this is completed, select MM+ under the molecular mechanics dialogue box in the setup menu. Do not adjust any of the options, as default values will be fine for the purposes of this example.

Under compute, choose Geometry Optimization that will find an optimal confirmation.

What is the energy of the optimized structure: _____________

Provide some dimensional information on the molecule presented. Number the carbons in the molecule and investigate at least 5 different angles and 5 different bond lengths:

Angles:

__________ __________ __________ __________ __________
 
 

Bond lengths:

__________ __________ __________ __________ __________

I. Theory

Semi Empirical methods are used to perform a quantum mechanical calculation rather than a molecular mechanics method. Semi empirical is selected as a default in the set-up menu. You can use semi empirical methods to perform the following:

· Single Point Calculation

· Molecular Dynamics

· Geometry Optimization

· Vibrations

· Coutour Plots

· Orbitals

· IR Spectrum

· UV/Visible Spectrum

II. Background

• Describes bond breaking
• Can be performed on any molecule
• Parameters are independent of chemical environment
• Interprets results with LCAO-MO theory
• Interprets stereochemistry and rates of many reactions involving "soft" electrophiles and nucleophiles in terms of the properties of Frontier orbitals
• Can be used on inorganics
• Can calculate heats of formations, dipole moments and electrostatic potentials

• Calculates only for valence electrons
• Neglects integrals for certain interactions
• Uses standard, non-optimized, electron orbital basis functions
• Uses parameters derived form experiment

• Extended Huckel
• "one electron" simplification that assumes no explicit interactions between electrons

• molecular orbitals
• most first and second row transition elements

• geometry optimization or molecular dynamics

• CNDO – Complete Neglect of Differential Overlap
• ground state electronic property of open and closed shell systems

• geometry optimization
• total energy calculations

• transition elements

• INDO – Intermediate Neglect of Differential Overlap
• same as CNDO but accounts for certain one-center repulsions between electrons in the same atom

• MINDO3
• better than INDO

• large organics
• calculations of electronic properties
• geometry optimizations
• total energy calculations

• transition elements

• MNDO
• same as MNDO3 but calculates heats of formations

• various organics

• transition elements

• AM1
• very accurate and the same as MINDO

• molecules with N and O

• transition elements

• PM3
• better made parameters than the other force fields

• IR and UV/Vis spectra
• organics

• ZINDO/1

• transition elements
• calculations of energy states and geometries of molecules

• ZINDO/S

• UV/Vis spectra with CI calculations

Not Good For:

· Anything else

V. Semi-empirical options

These options provide settings for any semi-empirical, quantum mechanical method that is chosen except for Extended Huckel. The semi empirical options dialogue box is split into various sections with sub categories associated with each section:

· Charge and Spin

· Total Charge

· Spin multiplicity

· SCF Controls

· Convergence limit

· Iteration limit

· Overlap weighting factors

· Sigma-Sigma

· Pi-Pi

· State

· Lowest

· Next Lowest

· Spin Pairing

· UHF

· RHF

There is also another option highlighted in the Semi-empirical Options Dialogue box. Above the OK option there is a key marked CI, which stands for configuration interactions. This option activates and sets options for a configuration interaction calculation in the CI dialogue box. This method is crucial in determining the UV visible spectra.

VI. CI dialogue box options

· CI Method

· None

· Singly Excited

· Microscale

· Orbital Criterion

· Occupied

· Unoccupied

· Energy Criterion

· Maximum Excitation Energy

VII. Log File

· Before running the semi-empirical calculations, go to the File menu and select Start Log.

· Name your log file as you would a word processing document (e.g., log.doc)

· Run the semi-empirical calculations, go back to the File menu and select Stop Log

· Exit Hyperchem and open the log file in Microsoft Word. This will give you the physical constants, as well as data on the minimizations

VIII. To use Semi-Empirical, or Not to use Semi-Empirical

· Make sure to run a Molecular Mechanics Geometry Optimization before running a semi-empirical calculation. This will decrease time of the

semi-empirical calculation.

· Semi-empirical is an advanced calculation tool. Unless you are specifically looking for something that requires semi-quantitative data, semi-empirical calculations are frivolous and time consuming.

· If you are using IR, UV-Vis, contour plots, or need physical constants, semi-empirical calculations are necessary

VIII. Illustration

Practical applications of CI calculations:

· Calculate UV spectra

· Calculate the energy of excited states

· Study the making or breaking of bonds, and change spin of couplings

· Capture the effects of London dispersion forces

· Describe a nearly degenerate state

· Study singlet-triplet states more accurately

IX. Further Readings or References

• Balevicius, M.; Lithuanian J. of Physics 1995, 35, 20 – UV/Vis
• Seeger, D. M., et.al.; J. Phys. Chem. 1991, 95, 6871 - IR
• Dewer, M. J. S.; J. Am. Chem. Soc. 1985, 107, 3902 – AM1
• Bingham, R. C.; J. Am. Chem. Soc. 1975, 97, 1285 – MINDO/3

I. Theory

• Generally more accurate than semi-empirical but will take longer
• Characterized by the introduction of an arbitrary basis set for expanding the molecular orbitals
• Characterized by the explicit calculation of all required integrals involving this basis set
• Calculations solve the Roothaan equations without any further approximation apart from the use of a specific finite basis set
• All the integrals over atomic orbital basis functions are computed and the Fock matrix of the SCF computation is formed from the integrals

2. Calculations

• Single Point Calculations and Configuration Interaction
• Optimization Methods
• Molecular Dynamics
• Vibrations
• Contour Plots and Orbitals
• IR spectrum
• UV/Vis spectrum

1. Theory

• Samples phase space by integrating numerically Newton’s equations of motion
• Accounts for thermal motion
• Molecules may contain enough thermal energy to cross potential barriers
• Simulations which calculate the future positions and velocities of atoms based upon their current values
• Classical total energy is conserved and the motion is faster (large K) near minima in the potential surface (small P)

• Possible conformations
• Thermodynamic properties
• Dynamic behavior of molecules
• Simulates bond breaking and forming

To run a molecular dynamic simulation:

· Geometrically Optimize in the preferred force field. If someone wants to go from a transition state to a stable molecule, optimizing may include manipulating the molecule, see BUILDING above.

· Choose Molecular Dynamics on the Compute menu. A menu will come up to select molecular dynamics parameters

Molecular Dynamics Parameters

· Times

· Heat time- 0ps

· Run time- 0ps

· Cool time- 0ps

· Step size- .001ps

· Options

· In vacuo- checked

· Periodic boundary conditions

· Constant Temperature- checked

· Bath relaxation time- .1ps

· Temperature

· Starting temperature- not checked- 0K

· Simulation temperature- 300K

· Final temperature- not checked- 0K

· Temperature step- not checked- 0K

· Data Collection period- 1 time steps

· Screen refreshment period- 1 data steps
 
 

· To monitor a value throughout the simulation, click on Averages...

· Select the parameter to monitor- you can monitor up to four

· Select Add -> This moves the parameters to average only.

· Use the same procedure to move them to Avg. & graph

· To monitor a parameter within the molecule (e.g. bond length)

· Select the portion of the molecule to be monitored

· Go to Name Selection, and create a name

· Go into Averages... on the Molecular Dynamics menu and

NOTE 2: It is unfortunate that Hyperchem’s molecular dynamics program does not work better than it does. The temperatures given do not relate in any predictable way to real temperatures, and it is offer difficult to reproduce any results. To try and produce any reproducible results, it is advised to use a macro through Excel, using very simple systems.

NOTE 3: It is possible that with a great deal of fine tuning, meaningful results could be obtained from of molecular dynamics, but let the reader be forewarned.
 
 

Also note that semi-empirical single point calculation will provide information regarding orbitals and contour plots of molecules. The orbital dialogue box allows the following to be seen:

· degeneracies and near gap degenericies

· HOMO-LUMO gaps

· orbital occupation scheme

· d-d splitting for transition metals

Selecting plot on the orbitals dialogue box will display a contour plot of the selected orbital with the options specified in the Grid option.

Contour plots will display electrostatic potential, total spin density, or total charge density. These can be computed by performing a single point calculation.

· Total spin density-- This plots the probability of finding more spin-up electrons than spin-down electrons at any point in space.

· Total charge density -- Plots the electron density function for molecular valence orbitals.

· Electrostatic potential -- Plots the electrostatic potential field due to the electronic charge distribution and nuclear charges. This is not available for Extended Huckel.

· Balevicius, M.; et.al; Lithuanian J. of Phys., 1995, 35, 20

I. Theory

Vibrational analysis graphically displays the normal modes associated with individual vibrations, as well as the IR vibrational spectrum. Vibrations of a molecule correspond to motions of atoms relative to each other. The trajectories of the nuclei involved are extensive, but can be generalized into the following categories:

· Stretching

· Bending

· Rocking

· Wagging

When performing a vibrational analysis it is important to keep in mind the structure of the compound of interest. Recall that there exist 3N-6 vibrational modes in any non-linear molecule (3N-5 for linear systems); where N is the number of atoms. Recall also that compounds, depending on their various modes of symmetry, can be Raman active, IR active, or Raman and IR inactive. From the vibrations calculated, it is possible to obtain the complete vibrational spectra.

In order to perform a vibrational calculation, the system of interest must be geometrically optimized using a semi-empirical force field. Refer to the Reference Manual for Hyperchem for a mathematical description of the vibrational calculations. Vibrational analysis performs the following tasks:

· Provides insight into the rigidity of the molecular framework

· Visualize normal modes corresponding to lines in the IR spectrum

· Helps identify unknown compounds by correlating predicted versus experimental vibrational frequencies.

· Differentiate minima from saddle points on a potential energy hyper-surface

II. Calculations to Obtain IR Spectra

• Draw your molecule and add H and model build
• Choose Molecular Mechanics and MM+
• Choose Geometry Optimization and a .01 gradient
• Choose Semi-Empirical and PM3 - make sure that CI is turned off

Do not choose Extended Huckel.

• Choose Geometry Optimization and a .01 gradient
• Choose Vibrations
• Choose Vibrational Spectra and find the wavelength you need

· L-click on the frequency of interest.

· L-click on animate vibration and click OK

• NOTE The spectra obtained through Hyperchem differ from actual recorded spectra. Hyperchem is best used as a tool to follow trends in a series of related molecules. For example, a series of 3-8 membered cycloketone rings were built and the frequencies of the carbonyl stretches were determined. In each case, the calculated frequency was about 400 cm^-1 larger than the literature values. By establishing a relationship such as this, you could make a similar uncharacterized molecule, and be able to predict with some accuracy the spectrum of this molecule.

• Further Readings or Referencs
• Seeger, D. M.; et.al.; J. Phys. Chem. 1991, 95, 6871

This can be used as an alternative to molecular dynamics. The bond angles, bond distances, torsion angles, the energy, and other parameters can be changed and monitored. Also, point charge or geometric optimization can be utilized within a macro. Overall, any function within Hyperchem can be monitored and manipulated through Excel.

· Writing a Macro

· To begin writing a macro, see Lesson 14 from the Getting Started Manual.

· To write an original macro, see commands on pp. 288-332 of the Reference Manual.

· When writing an original macro, it is easier to call up an existing macro, like plot.xlm, and change the lines of code to fit your needs. Do not edit the lines concerning the New Channel. These are standard for allowing Excel to communicate with Hyperchem. Also do not edit the lines from Compute.Results to =EXECUTE(channel "[query-response-has-tag(no)]").

· Examples included in Hyperchem are butane1.xlm and eascal.xlm which are different macros. The file butane1.xlm was used to monitor the energy output of the butane molecule at different torsion angles. The file eascal.xlm gets the point charge of each carbon in an aromatic ring using different semi-empirical force fields.

1) If I build two molecules in the workspace, why can’t I move one without moving the other?

If you want to move a molecule in the presence of others, make sure that multiple selection is on. Then hold the R-click down on the selected molecule. That molecule will move while the other remains stationary.

2) When I run a vibrations calculation and obtain the vibrational spectra, the corresponding frequencies do not correspond to those that would be expected on traditional IR data.

Hyperchem vibrational spectra only exhibit relative trends for the vibrational spectra. While the numbers obtained for each peak are, in some cases, drastically different from their expected value, they do follow consistent trends with each other. By animating the peaks, you can see what peak corresponds to which functional group in the molecule of interest.

3) When I obtain the UV/Vis spectra, the result does not produce a maximum wavelength near the expected value.

Make sure that when performing a single point calculation you are specifying the correct semi empirical method. For example, PM3 is best for organic systems, so it would be useless to use this on a compound like aluminum triiodide.

4) Hyperchem will not let me geometrically optimize my molecule.

Make sure that you add H and model build. Most functions will not be possible until this is done.

5) Hyperchem will not let me add additional atoms to a structure that has already been optimized or I get an error message stating that the valence limit has been reached.

Under the build menu select allow atoms. Go back to the workspace and make any additions necessary. Then add H and model build.

6) When I go to perform a single point calculation using semi empirical methods, I get an error message about spin pairing.

When this happens open up the Semi-empirical options dialogue box. Make sure that RHF is selected as the default. Run the single point calculation just as before you ran into the problem.

7) I put my system into a periodic box and I cannot remove it.

Choose the select molecules option. Highlight the molecules not associated with the periodic box. Now select complement selection, which will highlight all of the water molecules. Open the Edit menu and select clear. The dimensions of the box will still remain.

8) When looking at the vibrational spectrum, I cannot click on all of the peaks because they are too condensed.

In this case, use the zoom out bar at the top of the spectrum by moving it toward the right of the dialogue box. This will zoom in on a narrower frequency range to make it easier to select and animate those peaks which are difficult to see.

9) If I want to select a bond, I cannot because the entire molecule becomes highlighted.

Check the selection mode. If you are trying to select a bond and you end up selecting a molecule, then molecules is the selection mode activated.

10) I cannot see the stereochemical relationships in the structure of interest.

In this case, it would be advantageous to insert the internal axis for the molecule under the display menu. The internal axis only appears for sticks and dots rendering. Also, you can click on chirality.

11) I obtained an error message due to an unknown parameter.

There are two options: (1) ignore the error and continue with the calculation.

(2) Obtain the exact parameters from experimental data.

12) I obtained an error message to a half electron approximation or node equaling zero.

Refer to reference manual.