Lesson 7: MOLECULES
A synthetic drug is usually thought of as being a PURE. While this is generally the goal in
the pharmaceutical industry, a small amount of contamination is expected. Generally the
contaminants result from having a small amount of material needed for the synthesis remain
in the completed recipe. For instance, aspirin is made using vinegar (acetic acid) and a small
amount of acetic acid is therefore present in the final product. 1 Oddly enough, in the late
1950s, one drug impurity led to thousands of babies being born with birth defects. The drug
thalidomide was used as a sedative for pregnant women. The birth defects arose because in
the synthesis of the desired molecule, large amounts of a molecule with the identical
chemical structure, but with mirror opposite symmetry, was formed. Molecules with the
same formula but different symmetry are called ISOMERS. This mirror opposite of the
sedative molecule ISOMER had very dire consequences to the development of limbs in
unborn children.
Image Citation - blogs.nature.com
This is the first lesson in Unit 2 - a unit
relating to pharmacology. Pharmacology is a
branch of biology and medicine that studies
the mechanism of drug action. Drug action
depends upon the drug molecule itself. It also
depends upon how the subject who has taken
the drug uses the drug and how it is
metabolized in the body. In this first lesson,
you will revisit the basics necessary to discuss
these molecules. If the term "atom" is
unfamiliar to you, it would be wise to give
yourself a brief reminder of what atoms are and how they are built into molecules via chemical
bonds.
Objectives
After successfully completing this lesson you will be able to:
 name biologically relevant molecules and their functions
 recognize different versions of a molecular structure
 recognize functional groups (methyl, acetyl, hydroxyl, amine)
 understand the importance of proteins in our study of mood-altering drugs
Before you begin!
o Your ideas
 What is the difference between caffeine and chocolate?

Caffeine is a stimulant, but chocolate is not

Caffeine is a molecule, chocolate is not
1
http://www.aapspharmscitech.org/view.asp?art=pt030206
1
Lesson 7: MOLECULES


Caffeine and chocolate are highly related molecules, differing by a single
functional group
Caffeine is a drug, but chocolate is not
o Previously learned material
 One group of neurotransmitters is classified by the fact that all members have the
same functional group. What is that functional group?
 You previously learned that the membranes surrounding cells are made up of lipids.
In what way is that lipid covering helpful to cells?
 What role do proteins have in biological membranes?
 If you eat a mushroom, and ingredients in that mushroom acts upon serotonin
receptors in a way that is a lot like serotonin but there are important differences, you
would characterize the ingredients in the mushroom as being:

serotonin agonists

serotonin antagonists

partial serotonin agonists

partial serotonin receptors
Lesson 7: Molecules
Guiding Questions
1.
2.
3.
4.
5.
What is the relationship between atoms and molecules?
What are the biologically relevant molecules?
What types of molecules to drugs bind to?
How do related molecules compare to each other, how do they differ?
How does one read and interpret a molecular diagram?
Key Terms
 Atom
 Molecule
 Bond, covalent bond
 Carbon, hydrogen, oxygen, and
nitrogen
 Lipid
 Carbohydrate
 Protein
 Enzyme, catalyst
 Agonist, antagonist






Nucleic Acid
Hydrophobic
Functional group
Methyl, hydroxyl, amine, acetyl,
aldehyde
Receptor
Recycling transporter
2
Lesson 7: MOLECULES
Activity One: Video and Web Review
To reacquaint you with the periodic table, atoms, and why atoms are often found joined together into
molecules, watch this video: http://www.youtube.com/watch?v=hEFeLYWTKX0&feature=related As
you watch, keep in mind these guiding questions.
what is the relationship between atoms and molecules?
why will to hydrogen atoms be more stable when together in a di-hydrogen molecule?
what type of chemical bond forms when atoms share electrons?
what are the lines representing when you look at a molecule such as water?
O
H
H
What do "C", "N", "H", and "O" stand for on the periodic table?
One thing this video does not cover is the special affection we biologist have for the carbon atom. On
many a science-fiction show, earths species are often referred to as "carbon-based life forms". The
molecules of living things, or organic molecules, are almost all based on the versatile carbon atom.
Versatile describes something (or someone) with many capabilities. Visit two pages from Dr.
MaMahon's web site from the University of Wisconsin. The two pages to visit are the page on
"versatile carbon" and the one named "carbon usually forms four bonds".
http://www.chemeddl.org/resources/TSTS/McMahon/McMahon9to12pg/Introduction9-12.html
Carbon's are so versatile and so common that they are often "implied" in molecular diagrams as we'll
see later.
Activity Two: Biological Molecules
Many, but not all, biological molecules feature carbon. Water is rightly considered a biological
molecule. But our attention will be focused on some of the larger biological molecules. Many of
these are so ubiquitous (present everywhere) that you are probably very familiar with them just from
reviewing the nutrients in the foods you eat. At this Food and Drug Administration web site, view
the Nutrition Panel found on a Macaroni and Cheese product (found in the overview).
http://www.fda.gov/food/labelingnutrition/consumerinformation/ucm078889.htm
These are all biological molecules.
Fat
Cholesterol
Carbohydrate
Protein
Vitamins
3
Lesson 7: MOLECULES
Sodium, Calcium, and Iron are important minerals (atoms) whose intake we should monitor.
While all of these biological molecules are deserving of attention, in our course, we will focus on two
from this list and one that is not on this list.
Fats and cholesterol belong to the LIPID category of biological molecules. These molecules are waterfearing and you learned about a very important lipid in unit 2 - the phospholipid.
Proteins are biological molecules that do the majority of cellular work. Some proteins are receptors
(which can bind to ligands). Some are transporters (such as pumps and channels). Some are
enzymes - molecular catalysts that speed up chemical reactions. Each of these subtypes of proteins
will be important in our study of mood-altering drugs.
One biological molecule that is NOT found on a nutrition label, but which IS found in almost every
food we eat (food that comes from living things) is nucleic acid. The most famous nucleic acid is
DNA - deoxyribonucleic acid. RNA is the other nucleic acid. The reasons these molecules do not
show on a nutrition label is NOT because they are removed from food when food crops are
processed, but because they are not nutrients. We have all the necessary information in our bodies to
make our own DNA. We do not need to consume it. Likewise, while vitamin C is a nutrient for us, it
is NOT a nutrient for dogs. Dogs have the ability to make their own vitamin C.
TEST OF CONTENT
What is special about lipids in our study of mood-altering drugs?
Their hydrophobicity.
Their carbon composition
Their covalent bonding
Their methyl groups
What is special about proteins in our study of mood-altering drugs?
They are not nutrients, like carbohydrates and lipids are.
They serve as hydrophobic barriers in membranes
All neurotransmitters are proteins
Drugs bind to a variety of protein types when influencing how cells work.
Activity Three: Molecular Diagrams
You will be shown many different molecular diagrams in your study of mood-altering drugs. Here
are a few to get you started.
The molecule to consider first is ethanol. Ethanol is an alcohol and the main one found in beer, wine,
and other beverages. Ethanol's chemical formula is C2H5OH.
4
Lesson 7: MOLECULES
A ball and stick model of ethanol can be used to represent each of the atoms in different colors and
connected by sticks representing the covalent bonds between these atoms. Here is a ball-and-stick
model of ethanol. The carbons are gray, and the oxygen is red.
Ethanol can also be represented by a molecular diagram that provides a little less information about
the geometry of the molecule. The molecular diagram of ethanol showing ALL its atoms is:
But because biological molecules mostly have carbon, and because each carbon can form four bonds,
and because many of the atoms carbon bonds to end up being hydrogen, the SHORT CUT diagram
that represents ethanol is
O
Each line represents a bond. Bonds form BETWEEN atoms. Thus the left line, having
NO other notations must be carbon - carbon is IMPLIED if no other symbol is offered.
Similarly, the right line, having nothing on its left and an oxygen (O) on its right, is
a bond between carbon and oxygen.
O
So, the diagram above, could be relabled to more closely resemble the ethanol molecule diagram in
which all atoms are shown by applying carbons to all line ends. THEN, to account for all of carbon's
four bonds (and oxygen's two bonds), hydrogens are placed wherever necessary as shown:
H
H
C
H
H
O H
C
H
Now look at the molecular diagram of acetaminophen (the generic name for the pain reliever
Tylenol).
Unlike ethanol, this molecule has a carbon ring and a nitrogen. But
like ethanol, there is an OH group - a hydroxyl group. More on this
type of functional group in the next activity.
5
Lesson 7: MOLECULES
TEST OF CONTENT
How many carbons are in acetaminophen?
How many hydrogens are in acetaminophen?
Activity Four: Functional Groups
The hydroxyl we previously described - OH - is an example of a functional group (sometimes called
moiety). Functional groups are submolecular groups of atoms that are often responsible for a
particular function in the molecule or are related in terms of synthesis or metabolism of the
molecule.
The functional groups you will be exposed to are:
methyl (CH3)
hydroxyl (OH)
aldehyde (CHO)
aceytl (COCH3)
Which of these groups do you see on the acetaminophen molecule? OH is off to the left, COCH3 is
on the very right. Note that CH3 is part of COCH3, so generally we call it an aldehyde - it "trumps"
the methyl being more complete. But notice also that the OH on the left (and it is the same as HO) is
attached to a carbon (in the ring). Since the carbon is in a ring, it is not considered an aldehyde.
Methyl groups will be very important. For instance, caffeine's chemical name is tri methyl xanthine
and chocolate is di methyl xanthine. What does this suggest about the chemical comparison
between caffeine and chocolate? It should suggest to you that the molecules are the same with the
exception of the fact that on caffeine there is an additional methyl group. Methyls will often tell us a
lot about the potency of a drug. Among the stimulants, the rule is that more methyls means more
potent.
Acetyl groups are important when we consider analgesics (pain relieving drugs). Heroin is
morphine plus two acetyls. This dramatically alters the properties of morphine because the acetyls
enable heroin to cross the blood brain barrier much more quickly.
6
Lesson 7: MOLECULES
You've already seen the importance of amines, at least in part. Many related neurotransmitters are
MONO amines and because of that similarity are metabolized and produced by similar pathways.
Aldehydes will be important in our study of alcohols. Ethanol (beer/ wine) is metabolized into
acetyl aldehyde, but methanol (found in industrial fluids such as copier ink) is metabolized into
formaldehyde. Both are aldehydes, and both are toxic to cells.
TEST OF CONTENT
The molecule to the right is theophylline (the stimulant
found in tea). Like chocolate and caffeine, it is a xanthine.
What kind of xanthine is it?
Dimethyl
Trimethyl
Monomethyl
Activity Five: Molecules that Drugs Bind To - Receptors
Technically, any molecule that another binds to is a receptor. But often the molecule a drug binds to
is a receptor for another molecule made by the body. Molecules made by the body are called
endogenous. Endogenous means made from within. For instance, we make endorphins. These are
chemically related to morphine. Endorphin means Endo Morphine. Both bind to the same receptors
- opiate receptors (morphine is found in opium or poppy).
Drugs can bind in a way that is LIKE the endogenous molecule. Review Unit 1, activity 4. If it does,
it is a receptor agonist. Morphine is an opiate receptor agonist. Like endorphins, when morphine
binds to opiate receptors, a neuron with these receptors is inhibited.
Drugs can also bind in a way that is DIFFERENT from the endogenous molecule. When someone
overdoses on heroin or morphine, the treatment for them is to give them enough of the antagonist
"antidote" so that their receptors will fill with something other than the drug, which will help them
avoid the toxic effects the drug has in high doses. One such opiate antagonist is called
buprenorphine.
TEST OF CONTENT
Methadone is given to people who become addicted to heroin. Using methadone instead
helps them to avoid the withdrawal symptoms that happen when they try to quit and also helps
them avoid acquiring diseases associated with the needle delivery of heroin. Not only does
methadone help minimize withdrawal symptoms, it also can make a person euphoric or high.
Based on this decide if methadone is:
a receptor agonist
a receptor antagonist
a endogenous ligand
Activity Six: Molecules that Drugs Bind To - Recycling Transporters
7
Lesson 7: MOLECULES
From Unit 1, lesson X, you'll recall that neurotransmitters can be recycled for later use by the
presynaptic neuron. Some drugs work by altering the function of those recycling transporters.
Generally, drugs affect recycling transporters by blocking neurotransmitter reuptake. Some drugs
alter the function of these recyclers as well by causing them to work in reverse and dump
neurotransmitter out of the cell instead of bring the molecules back into the cell.
In both of these scenarios, more neurotransmitter is available in the synapse and for longer when a
recycling transporter is altered by a drug. If the neurotransmitter is excitatory, such as dopamine,
then the post synaptic cell will experience more and more action potentials.
The antidepressant, prozac, works as a recycling transmitter blocker. Prozac is a drug that blocks
serotonin recycling specifically. An unrelated drug, doxepin, blocks recycling of all monoamines.
Activity Seven: Molecules that Drugs Bind To - Enzymes
Receptors and recycling transporters are proteins. The last type of protein that drugs often impact
are enzymes. These enzymes could be catalysts for metabolism of neurotransmitter or other moodinfluencing brain molecules. For the drugs we will consider, when they bind to the enzyme they will
reduce or completely inhibit that enzyme's ability to do its job.
Enzyme function is a very important process with regard to mood-altering drugs. For instance, we
have an enzyme that alters heroin and turns it into morphine. Recall that the acetyl groups on heroin
enable this drug to pass into the brain very efficiently. But the acetyls must be removed before the
drug can bind to opiate receptors. So, in most people, an enzyme attaches to the heroin and removes
the acetyl groups. Imagine what would happen to someone who lacked this enzyme.
Some mood altering drugs act on the enzymes that metabolize endogenous molecules, such as
neurotransmitters. One drug that blocks an enzyme is aspirin. Aspirin is a pain-relieving drug that
works by inhibiting cyclooxygenase (or COX). Without cyclooxygenase, our ability to feel pain is
greatly diminished.
Activity Eight: Reading
Required Reading

Liska - "Receptor-Site Theory (1.6 in 7th edition)
 Introductory Biology text book - on atoms, bonds, and molecules
Internet
 http://www.chemeddl.org/resources/TSTS/McMahon/McMahon9to12pg/Introduction912.html
Supplemental Reading
Internet
 http://www.nytimes.com/2010/03/16/science/16limb.html (article on 50 years after thalidomide
and what we have learned)
8