Introduction to Molecular Modeling (Spartan)

NOTE: There are some Spartan04 manuals on the top of the bookshelf in S301 (ScienceCenter). You can borrow these, but they MUST BE RETURNED!!!!!

We will meet in S243 for the next 2 lab periods

Background Reading:

Introduction

This experiment will acquaint you with the use of the molecular modeling software that is on the NazarethCollege computer network. The program that you will be using is called Spartan 04, a product of Wavefunction, Inc. of Irvine, California. The ultimate purpose of this experiment is to familiarize you with the some of the physical properties of organic molecules. There are actually a variety of types of molecular model kits available to organic chemists. The simplest type is the kind that you have already purchased in the bookstore, the "ball and stick" type model. This type of model is adequate for a first course in organic chemistry, but it is not very accurate in terms of actual bond lengths and bond angles. For more accurate representations of the position of atomic nuclei and bond angles/lengths, the Dreiding models are useful. Perhaps the most realistic molecular representations are produced by "space filling" models. These models, which are primarily computer generated, show the volume of space occupied by nuclei and electrons. In fact, computer generated molecular simulations are the state of the art in terms of molecular modeling. Not only do they allow you to obtain the shape and general structural framework of the molecule, but you can also obtain far more sophisticated levels of physical data (e.g. molecular energies, electron density maps, dipole moments, etc.). During this experiment, you will get a good idea of the power of computer assisted molecular modeling.

The use of molecular models will be especially helpful in your study of stereochemistry: the actual and precise arrangement in space of atoms in molecules. An accurate understanding of stereochemistry will allow you to decipher the chemical consequences associated with atomic arrangements. Again, the computer has made the study of the stereochemical nature of organic molecules much easier to understand and visualize.

The total amount of information that can be generated from hand-held molecular models is really quite limited. We certainly can gain insight into the molecular connectivity and can visualize stereochemistry. In addition, hand-held models also give semi-accurate representations of molecular shape and dimensions. However, if we are interested in:

(a)determining precise three-dimensional molecular shape

(b)establishing intramolecular relationships (e.g. precise atomic positions, bond lengths, bond angles, etc.)

(c)computing molecular energies (e.g. steric energy, transition state energy, conformational energy)

(d)superimposing molecules (e.g. comparing stereoisomers, visualizing enzyme-substrate complex)

(e)storing and manipulating structural information

then, we will need to take advantage of computer-assisted molecular modeling (CAMM). CAMM allows us to use mathematical computation along with computer graphics programs to: (a) predict and visualize the shape of a molecule; (b) compare the shape with molecular properties; (c) examine how molecular interactions influence chemical reactions; and (d) investigate a system dynamically. The myriad of applications of CAMM includes the development of new drugs, enzymes, pesticides, chemical sensors, chemical microelectronics, and space age chemical materials. In summary, the advanced computational power and innovative software that has been recently developed has enabled CAMM to become an integral part of experimental design. In many cases, CAMM has accelerated the process of discovery and innovation.

Getting Started with CAMM:

CAMM involves a series of experimental steps. These steps include building the structure, refining the structure, displaying the structure, computation of selected properties, display of the properties, and storage of the information. The initial phase of any modeling experiment is the building phase. The second phase involves molecular modifications. The final phase involves computational optimization and analysis of your structure.

Modeling software normally includes programs that allow you to either build a molecule from scratch or to input molecular fragments from a structural library. The Spartan software that you will be using contains both of these options. In addition, Spartan contains a variety of functions that enable you to modify your molecule (e.g. changing the shape of the molecule and adjusting bond angles and atomic distances).

The final phase of molecular modeling is the optimization phase. A number of computational methods have been written to accomplish a variety of optimization goals. In general, the process of optimization involves the slight movement of atoms from their starting positions in conjunction with the simultaneous calculation of the structural (steric) energy. New structures are generated with lower energy. The process continues until no further adjustments lead to a lowering of energy. The end result is the "energy minimized structure". We generally refer to this process as geometry optimization.

The total steric energy associated with our optimized structure is the most widely used piece of information gathered from energy minimization routines. Its is derived by a computational method called molecular mechanics. Molecular mechanics is a force field method that is primarily used to calculate optimum molecular geometry. The molecule is considered to be a system of atoms that has a discrete set of ideal values for bond length, bond angle, torsional angle, and nonbonded interactions (steric). In order to optimize the structure, deviations from the ideal values are conducted. These deviations include bond stretching, angle deformation, and the introduction of torsional and steric strains. The total energy of the molecule is simply the sum of each of these influences:

Etotal = Estretch + Eangle + Etorsion + Esteric

The ultimate goal of optimizing a structure by molecular mechanics is to modify each energetic subset in order to find a molecular geometry that gives the lowest (minimum) value for Etotal.

One word of caution here -- It is important for us to realize that molecular mechanics algorithms are designed to locate the LOCAL energy minimum. The local minimum may or may not correspond to the lowest overall (GLOBAL) minimum. Molecular mechanics programs will not allow structural deviations that proceed through energy maxima. Therefore, it is useful for beginners to start with high energy structures and let the optimization proceed to the minimum on either side of the maximum (Figure 1).

Figure 1

For example, if we started at the star (energy maximum) the molecular mechanics algorithm would proceed downward to the left (to a LOCAL MINIMUM) or to the right (to a lower energy LCOAL MINIMUM). Notice that the global minimum may not be achievable in this case. Some software programs contain a dihedral driver that enables the user to proceed through high- energy structures during the optimization run.

Even with this limitation, molecular mechanics remains an ideal tool for examining the structure of molecules. Your experience in this experiment will be to introduce you to the "nuts and bolts" of running a modeling experiment and for you to gain an appreciation for the potential wealth of information that can be gained by such methods. The most important benefit gained will be a clearer understanding of the three dimensional nature of organic molecules and how that can influence the physical and chemical phenomena we will be observing throughout the year. The initial skills gained here will allow you to carry out more sophisticated modeling experiments in future courses.

Prelaboratory Preparation

You will want to get on a computer in Smyth 243 or 301, build a molecule of your choice (try something simple at first), and then manipulate it. Your manipulations should include the following:

  1. Build using the BUILD menu and the side template.
  2. Using the MODEL menu, visualize the different views of your molecule that are available (e.g. ball-and-spoke, space-filling, etc.).
  3. Manipulate the molecule -- rotate, enlarge, shrink, translate, etc. This can be performed by using the table below and is also summarized on the ColumbiaUniv. website (below).

keyboard / left mouse button / right mouse button
- / atom selection, X/Y rotate / X/Y translate
Shift / range selection, Z rotate / scaling
Ctrl / global X/Y rotate / global X/Y translate
Ctrl + Shift / multiple selection, global Z rotate / scaling
Ctrl (build mode) / fragment X/Y rotate / fragment X/Y translate
Ctrl + Shift (build mode) / fragment Z rotate / scaling
Alt / group selection, bond rotation / bond stretching
  1. Change colors and layouts.
  2. Measure and change parameters such as bond length, bond angle, dihedral angle, etc. using the GEOMETRY menu.
  3. View the SETUP menu to see how you will setup and submit calculations and surfaces -- try a couple out on your own.
  4. After you have submitted a job, visualize the results using the DISPLAY menu -- energies, surfaces, dipoles, orbitals, etc.

Details on using the SPARTAN software can be found at:

There are a number of companies (in addition to Wavefunction) who produce MM software including:

Chem3D (CambridgeSoft)
Cache Scientific (Fujitsu)
HyperChem (Hypercube)
ISIS (MDL Systems)
MacroModel (Schrodinger)
RasMol (academic)
SYBYL (Tripos)
VMD (Univ. of Illinois)

More general information on molecular modeling:

Part 1

Prelaboratory Questions

  1. Copy a table of accepted bond angles and bond lengths for the following -- Use your Jones text (or some other organic chemistry text from the science center, S301) or search for a website, but be sure to document:
  2. carbon-carbon single bond
  3. carbon-carbon double bond
  4. carbon-carbon triple bond
  5. carbon-oxygen single bond
  6. carbon-oxygen double bond
  7. carbon-hydrogen bond
  8. Draw a Lewis structure for each of the following alcohols and record the literature boiling point for each alcoholbelow. Are these polar molecules? How do you know?
  9. n-butanol
  10. sec-butyl alcohol
  11. isobutyl alcohol
  12. tert-butyl alcohol
  13. Provide a skeletal structure for the following compounds:
  14. 2-butanone
  15. butanal
  16. 2-bromobutane
  17. N-methylbutanamine
  18. Butanamide
  19. 1-butanol
  20. butanoic acid
  21. methylbutanoate
  22. Arrange the following alkene isomers in order of INCREASING stability according to the information presented in section 3.6 (page 115) of the Jones text.
  23. 1-hexene
  24. 2,3-dimethyl-2-butene
  25. 2-methyl-2-pentene
  26. (Z)-2-hexene
  27. (E)-2-hexene
  28. Draw all important resonance structures for the following molecules:
  29. NO3-
  30. CO32-

  32. Draw structures for cyclopropane, cyclobutane, cyclopentane, and cyclohexane.

Procedure

  1. Build and minimize each of the following hydrocarbons -- methane, ethane, ethylene, acetylene, 1-butanol, and 2-butanone.Obtain the equilibrium geometry at the AM1 level and tabulate bond lengths and bond angles.
  2. Build 2-bromopentane. LOCK the Br-C2-C3-C4 dihedral angle to a value of 0 (the large groups on the front and back of your Newman projection should be eclipsed -- verify before you proceed by rotational inspection of the molecule). DO NOT MINIMIZE. Instead, calculate a single-point energy at the AM1 level. Record the energy. Repeat the single point energy calculation for each of the following dihedral angles -- 60, 120, 180, 240, and 300 degrees. Tabulate energy for each dihedral angle.
  3. Build a hydrogen molecule. Perform an equilibrium geometry calculation at the AM1 level. Before performing any calculations, be sure to submit for determination of the HOMO and LUMO surfaces. Submit for calculation and surface determination. Upon completion, display the HOMO surface and then the LUMO surface. Examine the orbitals individually and together. Determine the energy difference between these two M.O.'s. Repeat the entire procedure for ethylene.
  4. Build and minimize each of the alcohols listed in prelaboratory question #2.Obtain the equilibrium geometry at the AM1 level. Before submitting your calculation, you should also request surface determination for an electron density and electrostatic potential map. Submit the job and, upon completion, display the electron density surface and then the electrostatic potential map. Identify regions of positive, negative, and neutral charge. Be sure to compare electron density surfaces with space-filling models for each alcohol. Also, record the dipole moments for each alcohol.
  5. Build and obtain the equilibrium geometryat the AM1 level for each of the molecules that you came up for prelaboratory question #3. Record the NET dipole moment for each. Also, observe any regions of the molecule that might be capable of either accepting or donating a hydrogen bond.
  6. Build models for each of the alkenes in prelaboratory question #4.Obtain the equilibrium geometry for each at the PM3 level. Record the energy of each isomer.
  7. Build models for the ions from prelaboratory question #5. Obtain the equilibrium geometry at the AM1 level. Before submitting your calculation, you should also request surface determination for an electron density and electrostatic potential map. Submit the job and, upon completion, display the electron density surface and then the electrostatic potential map. Identify regions of positive, negative, and neutral charge. Determine charges on each atom.
  8. Build each of the following cyclic hydrocarbons and calculate the heat of formation (semi-empirical PM3 level) for each: cyclopropane, cyclobutane, cyclopentane, and cyclohexane

Part 2

Prelaboratory Preparation

Draw each of the compounds that you'll be asked to model (see below) and look up/record the pKa value for the most acidic hydrogen in each molecule (you can use the tables on pages 18-22 of “SAM” and the table inside the back cover of Jones).

Procedure

(a) Acidity within a series of compounds

The acidity of a compound is typically measured by its pKa value. As we've seen in class, the smaller the value of the pKa, the more acidic that particular hydrogen will be. A number of factors are involved in determining the acidity of the hydrogen atom. However, it should be obvious that as we increase the positive charge character around a hydrogen atom, the more likely it is that the hydrogen can be donated (and, therefore, the more acidic that hydrogen is). The most effective way to view charge distribution is through an electrostatic potential map. That is exactly what you'll be doing in this part of the experiment.

In order to observe the change in acidity, you will need to BUILD, CALCULATE a wavefunction (energy), and produce each molecule’s electrostatic potential MAP. The procedure can be found in Chapter 4 of the On-line Tutorial and User’s Guide (pages 21-24) that is available through Spartan 04. Simply pull up an active Spartan window and all the way to the upper right-hand corner of the screen is the HELP menu. Select “On-Line Help” and then select the “Tutorial and User’s Guide” link. The first series is completely outline for you. The subsequent series will need to be acquired in a similar fashion.

(1)Series 1: formic acid, benzoic acid, acetic acid, trichloroacetic acid, dichloroacetic acid, chloroacetic acid, and pivalic acid

(2) Series 2: butanoic acid, 2-chlorobutanoic acid, 3-chlorobutanoic acid, and 4-chlorobutanoic acid

(3)Series 3: 1-butanol, cyclohexanol, phenol

(4)Series 4: ethane, ethylene, benzene, acetylene

(5) Series 5: propanal, 3,3-dimethyl-2-butanone, acetophenone, N,N-dimethylpropanamide, pivalic acid

(b) Energy of Dissociation

Build acetic acid and its corresponding conjugate base anion (acetate). Submit each for single point energy using a Hartree-Fock 3-21G* calculation. You may have to first submit for a semi-empirical AM1 calculation before acquiring the Hartree-Fock data. In either case, be sure to submit the TOTAL CHARGE for all conjugate bases as ANION.

Repeat the entire process for tricholoracetic acid/trichloroacetate anion and chloroacetic acid/chloroacetate anion.