4-H Club 1
“The many faces of oxygen”
In this activity, the candidate will explore this concept by examining the structures of several
pharmaceutical compounds that contain oxygen. Candidates will apply background knowledge
to explore how the structural context of the oxygen atom affects its properties which, in turn,
will determine its function. For this module, candidates will download and apply a no-fee
chemical structure drawing software package called Symyx Draw (formerly called ISIS Draw).
Problems:
1. Shown below is the structural formula of tramadol which is used for treating moderate to
severe pain and is available in oral dosages or as an injection. The structure has several Ocontaining groups. One group is labeled with a 1.
a. Look at the O-containing group labeled #1.
Name this group, identify it is not acidic,
weakly acidic, or strongly acidic and why you
1
identified it as such. The functional group at
location #1 is a hydroxyl group. Since the bond
has no double bound one single bond away
from it, there is no aromatic ring and it stays
localized, therefore it is not acidic.
b. Is the structure shown here the one that would
predominate in an aqueous solution at pH 7.4
(blood)? If not, then explain how the structure would need to be modified. Since the
pKa of tramadol is 9.41 and is not acidic, it will accept the protons therefore making it a
+ charge. The pH of the solution is 7. Comparing the pH and pKa the pH is less than the
pKa which shifts it towards the acidic side. Since the protons will bind the pH will shift
more towards the acid in favor of the + charge.
2. Shown below is the structural formula of morphine. Morphine is used to treat moderate to
severe pain. The structure has several O-containing groups. One group is labeled with a 1.
1
a. Look at the O-containing group labeled #1.
Name this group, identify it is not acidic, weakly
acidic, or strongly acidic and why you identified
it as such. The functional group at location # 1 is
called a phenoxyl group. It is an O-H group with
a double bond located one single bond away;
however that is part of an aromatic ring with 6 e-.
This situation exhibits weak delocalization. The
pKa is typically in the 8 – 11 range. This group
is considered to be weakly acidic.
4-H Club 2
b. The phenoxyl group (#1) has a pKa of 9.4. Assuming no interaction between groups,
what percentage of the base form of phenoxyl group would be present in blood (pH =
7.4)?
pH = pKa + log10 (base/acid)
7.4=9.4 + log 10 (b/a)
-2 = log 10 (base/acid)
100 = ( base/acid)
100 = x/100-x
100 (100 – x) = x
10,000 – 100x = x
10,000 = x + 100x
10,000/101 = x
99.09 = x
The percentage of the base form of the phenoxyl group in blood plasma is 99%.
c. Connection to Module B: Identify if morphine is a chiral compound. Why or why not?
Morphine is a chiral compound. There are multiple carbon atoms that have four
different substituents bonded to them. There are five chiral centers around Carbon
atoms in morphine. The chiral centers at carbons 3, 9 and 14 are designated as ‘R’
while those at 6 and 13 are ‘S’.
3. Below is the structural formula of aspirin, a pharmaceutical drug used as an analgesic to
relieve minor aches and pains, with a carboxyl group attached to it.
a. The pKa of the carboxyl group, labeled 1, in aspirin is
3.5. Is the structure shown here the one that would
1
predominate in an aqueous solution at pH 5.5
(approximate pH in the small intestine)? If not, then
explain how the structure would need to be modified.
Since the pKa of the carboxyl group, #1, in aspirin is
3.5 it will dissociate in the small intestine which will
give it a negative charge. The pH of the small
intestine is 5.5. Comparing the pH and the pKa, the
pH is greater than the pKa, which shifts it towards the
basic side. Since the proton will dissociate at pH 5.5
the base form of the carboxyl group will predominate therefore the negative form will
dominate.
b. Connection to Module B: Identify if aspirin is a chiral compound. Why or why not?
Aspirin is an achiral compound since there is no carbon atom bonded to four different
chemical groups.
4-H Club 3
c. Illustrate the relevant acid-base reaction for the carboxyl group of asprin.
Asprin
neutral acid
negative base
d. Aspirin has a pKa of 3.5. The pH of the stomach is about 1, while the pH of the intestines
is about 5.5 Apply the Henderson-Hasselbalch equation to calculate the percentages of
the aspirin is in the base form in the stomach (pH 1.0). Calculate the percentage in the
base form in the intestines (pH 5.5).
Stomach pH – 1 intestine pH – 5.5
pH = pKa + log10 (base/acid)
aspirin pKa 3.5
1 = 3.5 + log 10 (base/acid)
2.5 = log 10 (base/acid)
0.0032 = ( base/acid)
0.0032 = x/100-x
0.0032 (100 – x) = x
0.32 – .0032x = x
0.32 = x + .0032x
0.32/.9968 = x
0.32 = x
5.5 = 3.5 + log 10 (base/acid)
2 = log 10 (base/acid)
100 = ( base/acid)
100 = x/100-x
100 (100 – x) = x
10,000 – 100x = x
10,000 = x + 100x
10,000/101 = x
99.09 = x
The percentage of aspirin in the negative base form in the stomach is 0.32%. The percentage of
aspirin in the negative base form in the intestines is 99%.
4-H Club 4
4. Find an online reference to view the structures of the 20 DNA-encoded -amino acids.
a. Identify, by name, the 5 amino acids that contain an oxygen group in the side chain
(excluding carboxyl groups), and list the 3-letter and 1-letter codes for each.
Important: Look only at the side chain.
Name of amino
acid
Asparagine
Glutamine
Tyrosine
Serine
Threonine
3-letter code
Asn
Gln
Tyr
Ser
Thr
1-letter code
N
Q
Y
S
T
b. For the 5 amino acids you listed in the above table, identify the organic name of the
O-containing group that is found in the side-chain.
Name of amino acid
Asparagine
Glutamine
Tyrosine
Serine
Threonine
Organic Name
amide
amide
Hydroxyl
Hydroxyl
Hydroxyl
c. Identify the side chains that will confer positive charge in biological systems. Are
there any groups within the side chains of these amino acids that will confer negative
charge? Asparagine, Glutamine, Tyrosine, Serine, and Threonine WILL all have a
positive charge in biological systems. Asparagine and glutamine are POLAR
molecules and will have both negative and positive charges associated with it.