Discovery Based Research for Undergraduates: The Pencillin Lab

Overview: This discovery-based laboratory introduces students to combinatorial chemistry through the synthesis of new analogs of penicillin, the biological activities of which are then tested with a cell-based assay. Students first allow 6-APA (6-aminopenicillanic acid) to react with a variety of acyl chlorides. The reaction products are isolated as potassium salts and diluted to a range of concentrations. These solutions are then added to test tubes of bacterial broth to test the effects of the new penicillin analogs on bacterial growth. After all results are collected, the students share their findings, giving the class an opportunity to cooperatively analyze the structure-bioactivity relationship of their compounds.

Spring 2007: The first version of this experiment was incorporated into part of the Tufts University Organic Chemistry 54 Laboratory course during the spring of 2007. Students chose from eight acyl chlorides which were available in the chemistry stockroom.

Summer 2007: Using the feedback from Tufts students and the Teaching Assistants, Juniors Laura Truhlar (Tufts University) and Mark Williams (Morehouse College) revised the laboratory as part of their HHMI Summer Research Experience. They improved the synthesis process by carrying out the reaction at room temperature, and made the experiment safer by switching to a less toxic organic solvent. Mark and Laura also improved the biological assay by measuring optical density (OD), resulting in a more manageable dataset than the original biological assay. Additionally, the number of possible acyl chlorides was increased from the eight original to a total of 20 acyl chlorides, allowing for a greater variety of penicillin analogs.

Laura and Mark will have the opportunity to mentor other undergraduates in the spring of 2008, when the penicillin laboratory will be a part of Organic Chemistry 54 at Tufts. Additionally, we are contacting faculty at Morehouse College to see whether the chemistry department there would like to include the lab in their introductory organic course.