HONR 210:  MEDICINE - EAST MEETS WEST

Lab 4:  Molecular Modeling 1 - Organic Molecules

Introduction

In this “dry” lab you will learn to build models of some simple organic compounds, learn to draw structural formulas from molecular formula, understand the concept of isomers, and become familiar with the important functional groups in organic molecules.  This lab will be a prelude to the next lab, in which you will examine computer models of large biological molecules like DNA and proteins.

Organic compounds, the kinds that are most abundant in life forms, are based on only one element (carbon - C) along with a few other small nonmetals (principally hydrogen - H, oxygen - O and nitrogen - N).  Carbon is unique among the elements because it has the ability to form an almost limitless number of compounds.  Organic compounds usually involve a large total number of atoms. 

First we must understand some simple chemistry.  There are many more elements than the 4-5 postulated by the early Greeks.  There are 92 naturally occurring elements – substances that can not be broken down into simpler substances by any physical (melting, boiling, evaporating, condensing, etc) or chemical techniques.  Different elements are composed of different types of atoms that differ in their mass.  The simplest element is hydrogen (H) composed of a nucleus with one proton (with a positive charge) and one electron (with a negative charge).  The mass of the proton is about 2000 times that of the electron, so for our purposes we can neglect electrons as a contributor to the mass of the atom.  The next heavier element is helium (He) which has a nucleus with 2 protons and two electrons.  In addition, He has two neutrons (think of them as neutral protons with the same mass as a proton) in the nucleus.  Chemists use an arbitrary mass scale where the mass of 1 neutron or proton is 1 atomic mass unit or 1 AMU.  Hence a hydrogen atom has a mass of 1 and He has a mass of 4 (two protons and two neutrons).  Our modern notion of the atom, that you studied in many high school science classes, is that the nucleus is small and densely packed with protons and neutrons, with electrons (negatively charged) moving around the nucleus.   Different elements have different atoms with a different numbers of protons and hence electrons.  Two or more atoms can come together to form a stable, polyatomic structure called a molecule (Example:  H₂O).  When two atoms approach each other, their outer electrons can be given, taken, or shared with the other element.  This give and take of electrons is the glue that holds the atoms of a molecule together.  Since an oxygen atoms has a mass of 16 and each hydrogen has a mass of 1, the molecular mass of one water molecule is 18.  

Organic molecules typically involve the sharing of electrons between two atoms.  This sharing of electrons leads to bonding of the atoms.  For our purposes, in an organic compound (that contains C, H, and O and/or N) a bond forms when the atoms share two electrons.  We represent the two shared electrons representing the bond as a line between the two participating atoms.  Chemical reactions involves making and breaking of these bonds to produce new combinations of bonded atoms.  The nucleus does not change in chemical reactions.  If it did, the changed atom would become a different element (with a different number of protons and neutrons) and the dreams of the alchemists (to change lead into gold) would be realized.  (The nucleus does change in thermonuclear reactions at high temperatures.  Hydrogen nuclei (1 proton) can fuse to form a Helium nucleus (2 protons) in a reaction that occurs in the hydrogen fusion bomb and in the sun.  The uranium nucleus (92 protons) can split by a fast moving neutron into barium (56 protons) and krypton (36 protons) nuclei in a fission bomb (the kind used in Hiroshima). The main elements we will study in lab are C, H, O and N.  These are the most ubiquitous in organic molecules.  Millions of different organic molecules can be made.  A few rules can simply the study of their structures.  Generally, different atoms can form different numbers of bonds, since they each require a different number to make them stable when they are found in molecules.   Carbon usually forms 4 bonds to other atoms, nitrogen 3, oxygen 2, and hydrogen 1.  Many organic molecules contain chains of C atoms bonded to each other with some many H's and a few O's and N's attached to some carbon atoms.  Carbon, N, and O can also form multiple bonds in which more than 1 bond (each with two electrons) can attached two atoms together.  

Probably the best way to introduce yourself to organic chemistry is to physically build some simple molecules using a set of models.  Working in groups of two, you will be building some models, using kits that contain different color balls representing atoms of different elements.  Each ball (atom) has the proper number of holes bored in it to represent the number of bonds it can form.  The holes are placed so that the bond angles are correct in the finished compound.  Double and triple bonds can be made using the longer bonds  

The model kits prove to be useful for only small molecules.   Large molecules, such as proteins or nucleic acids, contain 1000's of molecules bonded together.  To study these we must computer graphic models.  In addition to making physical models of atoms, you will also view computer simulations of the same molecules using a web-based program called Chime.

Part 1:  The Hydrocarbons  Draw your models for each structure in the chart below.

 1.      Using one of the carbon atoms, four hydrogens and four single bonds, make the molecule methane (CH₄).  Note its 3 dimensional  tetrahedral nature (angles 109^o) that make it so difficult to draw on paper.  Draw the molecule below in two ways by replacing the A, B, C, and D with Hs and placing a C at the point where the bonds meet.  The planar representation is easier to draw but suggest bond angles of 90 degrees.  In the tetrahedral form, the wedging represent bonds coming out of the plan of the paper (solid wedges) or into the plan (dotted wedge).

2.      Using two carbons make a model of ethane (C₂H₆).  Then draw its structure below showing the tetrahedral nature of the bonds to C.

3.      Make a model of the molecule propane (C₃H₈).  Hydrocarbons are often referred to as a straight chain compounds.  After observing the geometry of the three carbons in propane, is it truly a straight chain?  Draw propane's structure below..       

5.  Many hydrocarbons contain double  bonds.   Organic compounds containing a double bond are called alkenes and have an -ene ending.  Some molecules have a series of carbon atoms connected into a cyclic ring structure.  Make models of the following molecules and draw the structure of each.   Use the longer, flexible bonds when making each of the double bonds.

a)       ethene, C₂H₄                                          

b)       propene, C₃H₆ (note:  this contains only 1 double bond)    

c.      cyclobutane, C₅H₁₀                                 

Viewing Computer Models

When viewing large biological molecules like DNA or proteins, it is almost impossible to use physical models.  These structures are most easily viewed using computer graphics.  In the next lab, we will study DNA and proteins using web-based molecular graphics.  For the rest of this lab, you will continue study small organic molecules by building physical models AND by viewing the same molecules through the computer. 

The program used for viewing these molecules is Chime.  The advantage of using computer modeling is that the molecule can be rendered in a variety of ways with a simple click of a button.  A molecule can be rendered in a variety of ways, including:

• wire model:  bonds between the atoms are shown as lines, without showing the atoms.  Atoms are located at the ends of lines and at the bend point between two attached lines

• tube model:  same as wire model but the bonds are shown as tubes, not wires

• ball and stick:  the atoms are shown as balls, with the connecting bonds shown as tubes

• space filling:  no bonds are shown but the actual size of the atoms are shown. Bonds connect adjacent atoms

• wire plus dot surface:  the size of the atoms are shown by a sphere of dots representing the size of the atoms, with the bonds shown as lines visible within the dot sphere. 

These are illustrated by selecting the link below and clicking on a series of different command buttons to change the rendering of a small molecule, acetic acid.

Chime Model: Acetic Acid

You can manipulate the molecule with the following mouse commands.

To rotate the molecule

(a) around the x-, or y-axes: 

Hold down the left button and drag the arrow across the screen in whichever direction you wish the molecule to rotate (vertical rotates around x-axis, horizontal around y-axis);

(b) around the z-axis: 

Depressing the right mouse button while holding down the keyboard shift key and moving the arrow horizontally causes rotation around the z-axis.

To zoom in on the molecule:
depress the left button while holding the keyboard SHIFT key down; then drag the mouse arrow downwards. Moving the mouse in the opposite direction zooms out.

To reposition the molecule in the frame:
depress the right button while holding the keyboard CONTROL key down and drag with the mouse to move the molecule within the frame.

Now that you are familiar with the different rendering styles, you can go to any Chime model and render it in anyway you wish by selecting from a series of options available by right-clicking on the image of the model.  Some of the most useful commands are shown below:

To edit the molecule, click on the molecule with the right button to reveal a menu:

• Mouse gives a summary table of the actions described in more detail here.
• Rotation starts automatic rotation of the molecule from left to right; click again to stop the rotation;
• Display has 4 available options:
Wireframe - shows the bonds and basic skeleton of the molecule.
Stick - makes the bonds thicker and more visible.
Ball & Stick - shows the atoms as balls joined by stick bonds.
Spacefill - represent the atoms as solid spheres.
• Options sub-menu includes:
Dot surface - used to superimpose a semitransparent image of the surface of the molecule over its skeleton.
Slab mode - shows those parts of the molecule which are to the rear of a plane through it.
Specular - adjusts the 'shininess' of the atoms.
Shadows - adds shadows to give better definition.
Labels - adds labels to certain atoms and groups.
Stereo Display - gives a 2nd image for stereo viewing.
 

Use these mouse commands to manipulate the computer models of the remaining molecules in this lab exercise.

Part 2:  Functional Groups

Most biological organic molecules also contain atoms of oxygen (O) and nitrogen (N).  Groups that contains these atoms are called functional groups.  They are very important and common in organic and biochemistry.  You will build some of these below.  Also you will find interactive molecular graphics images of the same structures.  To view these interactive models, you must use a PC (not Mac)  in one of the public access lab.  Using your kits, build at least two of the following organic compounds which contain a functional group and write the molecular formulas (C_xH_yO....) of each below the structure. Then compare your built model with the molecular graphics displays.  For the rest, just view the molecular graphics displays on the computer, while changing the rendering of the display by right-clicking on the molecules, and selecting display and the appropriate form you wish.  Also select options, dot surface, van der Waals surface to see the dot surface of the atoms while still seeing the bonds underneath.  Remember the color scheme for the different atoms:

Functional Group	Generic Structure	Example	Structure	Computer Structure
alcohol		ethanol
aldehyde		ethanal
ketone		acetone
carboxylic acid		acetic acid
ester		methyl ethanoate
amine		ethyl amine
amide		acetamide
aromatic		benzene

Part 3:  Stereoisomers 

Stereoisomers are isomers of molecules that have the same molecular formula and the same connections between atoms but differ from each other in the way the atoms are pointing in space.  Some molecules are actually mirror images of each other.  Your left hand is the mirror image of your right hand.  The fingers are all connected in the same order, but clearly your hands are not superimposable on each other.  Any molecule or object that displays such a property is called chiral.  Pairs of mirror images isomers of molecules that can't be superimposed on each other are stereoisomers.  Build both stereisomers of the molecule below (bromochloroiodomethane) and demonstrate to yourself that they aren't superimposable on each other.  Hence they are different molecules.  Verify this by rotating the 3D models until you are convinced that they are different molecules.

Now build 2 apparently different models of CH₂BrCl.  Are they superimposable?  Is CH₂BrCl  chiral?

LABORATORY REPORT Lab 4:  Molecular Modeling 1 - Organic Molecules }

Names:  

Hand in the entire lab handout with your drawn structures for all the examples given.  In addition, draw line structures for each of the 3D molecules shown below, and indicate the functional group in each.  Do this by comparing these models to Part 2: Functional Groups above.