4-H Club 1
Module C: Core Content Activity 1: Identity Crisis: The many faces of nitrogen
Corrections are in red
2. Shown below is a structural formula for the hallucinogenic drug, LSD. There are three
nitrogen-containing groups in this structure, labeled 1, 2, and 3.
a. As in problem 1, the N atom in each of these groups has a nonbonding electron pair.
Your friend is again insistent that each N must therefore be a relatively strong base
with pKa values in the 8 – 11 range. Evaluate your friend’s proposal. N-1 is not basic
because it is attached to a carbonyl group. N-2 has a non bonding electron pair that is
localized and no double bond on single bond away from the nitrogen, so it is strongly
basic. N-3 has a non-bonding electron pair; there is a double bond one single bond
away from the nitrogen, and the ring that is aromatic so the non-bonding pair is not
needed for the ring, so it is not basic.
b. The indole ring (group 3) includes an N-H bond. Another biologist friend suggests that
the N could act as an H+ donor. You know better. Explain. Acids are H+ donors and
this bond is weakly basic because the non-bonding electron pair is not needed to
complete the aromatic ring so, it would act more as an H acceptor. The N with –
charges are not normally observed.
3. Shown below is a structural formula of Losartan, a pharmaceutical drug used to treat high
blood pressure. It is marketed as a potassium salt. The structure has two nitrogencontaining groups, labeled 1 and 2..
c. Analysis of UV spectrophotometric titration data of losartan in aqueous solution is
able to resolve two pKa values, 3.6 and 4.8, corresponding to the tetrazole and
imidazole ring systems, respectively. Apply the Symyx Draw software to illustrate the
relevant acid-base reaction for the imidazole ring and for the tetrazole ring.
3.6
Tetrazole
Acid
Negative Base
4.8
Imidazole
Acid
Neutral Base
4-H Club 2
5. Find an online reference to view the structures of the 20 DNA-encoded -amino acids. For
example, you could try http://www.bio.davidson.edu/courses/genomics/jmol/aatable.html.
b. For the 6 amino acids you listed in the above table, identify the organic name of
the N-containing group that is found in the side-chain.
Name of amino acid
Lysine
Arginine
Histidine
Asparagine
Glutamine
Tryptophan
organic name
Amino group
Guanido group
Imidazole group
Amide group
Amide group
Indole ring
a. 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?
Lysine, Arginine, Histidine, WILL all have a positive charge in biological
systems. But Tryptophan is NONPOLAR so it does not have a charge associated
with it.
“The many faces of oxygen”
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 if 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 the OH group labeled 1, there is no
aromatic ring and the electron pair 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 of the amine group of tramadol
is 9.41 and is not acidic, the N will accept a proton therefore giving 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.
4-H Club 3
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.
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 of
the - charges. This situation exhibits weak
delocalization. The pKa is typically in the 8 – 11
range. This group is considered to be weakly
acidic.
b. The phenoxyl group (#1) has a pKa of 9.4.
Assuming no interaction between groups, what
percentage of the acid form of phenoxyl group
would be present in blood (pH = 7.4)?
pH = pKa + log10 (base/acid)
1
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 acid 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 5, 9 and 14 are designated as ‘R’
while those at 6 and 13 are ‘S’.
Structural diagram of morphine with chiral centers labeled.
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
and list the 3-letter and 1-letter codes for each.
Important: Look only at the side chain.
Name of amino
acid
Aspartole
Glutamole
Tyrosine
Serine
Threonine
3-letter code
Asp
Glu
Tyr
Ser
Thr
1-letter code
D
E
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 will have a negative charge and strongly acidic,
Tyrosine will have no charge and be weakly acidic, and Serine, and Threonine WILL
all have no charge and will not be acidic in biological systems.