Page 23 - Medicinal Chemistry Self Assessment

1. Shown below are the structures of cefotaxime, nitrofurantoin, atenolol, and ezetimibe. Each of these drug
molecules contains one ionizable functional group. The pK a values have been provided.
for cefotaxime at a plasma pH of 7.4, nitrofurantoin at a urinary pH of 6.1, a stomach pH of 1.8.

Nitrofurantion
Cefotaxime
pK = 3.4
pK = 7.1
a
a
12 b. For each functional group indicate whether it would be primarily ionized or primarily unionized at a
Medicinal Chemistry Self Assessment
Atenolol
pK = 9.6 Ezetimibe
a
pK = 10.2
a
2. In the previous question, we examined four pK values in three different environments for a total
a
of 12 different scenarios. Which of these 12 scenarios allow you to use the Rule of Nines to calculate
the percent of ionization of the functional group in the specific environment? Identify the specific
scenarios and use the Rule of Nines to calculate the percent of the functional group that would be
ionized.
3. Shown below is the structure of natamycin. It contains two functional groups that could be potentially ionized.
The pK a values for natamycin are 4.6 and 8.4.
3. Shown below is the structure of natamycin. It contains two functional groups that could be poten-
tially ionized. The pK values for natamycin are 4.6 and 8.4.
a
O OH
O OH

H 3 C O OH O COOH

O O CH 3

Natamycin
H O OH
NH 2

a. Match the pK values provided to the appropriate functional groups and identify if the functional
a
group is acidic or basic.
b. Using the Henderson-Hasselbalch equation, calculate the percent ionization that occurs for each
of these functional groups at an intestinal pH=6.2.
4. The most basic functional group present within the structure of ranitidine has a pK a value of 8.2. Identify this
Page 1 of 2
functional group and calculate the pH that is necessary for this functional group to be 70% ionized.
4. The most basic functional group present within the structure of ranitidine has a pK =8.2. Identify this
a
functional group and calculate the pH that is necessary for this functional group to be 70% ionized.

Ranitidine

Answers can be found in Section 2.3 [this will be linked to section 2.3 title]
Note: The questions in this chapter are related to Chapter 4 in Harrold MW and Zavod RM, Basic Concepts in
Medicinal Chemistry, American Society of Health-System Pharmacists, ©2013.

Page 2 of 2