Shakespeare on Acid: To ionize or not to ionize?

This lesson, created by Graciela Unguez, Erika Abel, Vanessa Castleberry, Rizalia Klausmeyer, Aaron Snead, Martina Rosenberg, William S. Garver, and Marcy Osgood for the National Academies Summer Institute for Undergraduate Education in Biology uses clickers, pair and share, and other exercises to help students "understand the effect of environmental pH on the ionization status of weak acids and weak bases."   This activity addresses "some of the most common misconceptions related to pH, pKa, and the behavior of weak acids in aqueous solutions. It begins with a medically relevant example (absorption of a commonly used drug, aspirin); it then addresses definitions of pH, pKa, ionization, acids and bases; it compares and contrasts pH and pKa; illustrates the effect of environmental pH on ionization state of a weak acid; and returns to the initial medical example, which the students now address in terms of the tidbit topic."  

The authors note, "Understanding and using the relationship between pH and pKa is difficult for all levels of students, from those in freshman introductory chemistry classes, through medical school courses. It is also one of the most important concepts for understanding how certain drugs and other substances can enter cells, and effect change."

 (Text from the Yale Center for Scientific Teaching's Teachable Tidbits).

Below is a sample lesson sequence:

Time (min)

Learning Outcome(s)


Explanation, notes, suggestions, tips

1 hour

Students should be able to:

Recall the definition of pH and pKa

Explain that pKa is a measure of how easy it is to remove a proton from a molecule


Before Class:

Read related textbook chapter portion and take publisher’s prepared online quiz

Online quiz should be targeted to determine whether students have corrected any misconception that high pH is associated with high [H+]

Online quiz should identify similar misconceptions about pKa values

5 minutes

Apply in medical context

Intro of aspirin example (the hook)

Other interesting things may come up here...what if you have food in your stomach, etc.

5 minutes


Rank weak acids with known pKa according to willingness to donate a proton

Clicker question and discussion

It may be necessary to review Le Chatelier’s Principle if students struggle with this preparatory information

10 minutes

Predict ionization of a weak acid in aqueous environment where pH<pKa, pH=pKa, and pH>pKa

Stickie note activity and group comparison/discussion

Depending on class size this activity can be adjusted.  It is visually stimulating to actually have the students come to the white board and affix their sticky notes to drawn beakers of aqueous solutions at different pHs.  The pH 7 beaker is critical as pH=pKa and this situation is not discussed in preparatory material

10 minutes

Predict ionization status of a drug with ionizable groups in stomach versus small intestine


Relate ionization status to a health endpoint: permeability of membrane to ionizable drugs under variable pH conditions


Using aspirin as an example, have students determine whether the drug is charged or uncharged in the stomach and small intestine


Ask students to consider the characteristics of the cell membrane and determine absorption in the two compartments

It may be helpful to have students identify the ionizable group on aspirin.  Some have difficulty identifying ionizable functional groups, initially.


Ask students what questions this brings to mind.  Perhaps stimulate discussion by asking what the effect of taking aspirin plus an antacid might be


The powerpoint below provides detailed notes to the instructor and can be implemented along with the lesson.
Additional handouts and materials are below.

This activity was contributed by Yale University.

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