High Speed Chemistry

From what is affectionately referred to as “the pit”—the basement level of the Roy and Diana Vagelos Laboratories—top Penn chemistry professors and administrators, alongside their Merck and Co., Inc. collaborators, recently announced the expansion of their state-of-the-art High Throughput Experimentation (HTE) laboratory. With the help of a grant from the National Institutes of Health, the chemistry department acquired two new pieces of instrumentation—a mass-directed liquid chromatograph and an ultra-performance liquid chromatograph—that will improve upon the lab’s already leading edge efficiency. 

“As far as we can tell, nobody in the world has this kind of technology at their disposal. It will enable us to continue a number of ongoing NIH-funded initiatives in the department and University, and with collaborators outside the University,” says Professor of Chemistry Marisa Kozlowski, one of four primary investigators attached to the lab. The other PIs are Gary Molander, Hirschmann-Makineni Professor of Chemistry and Department Chair; Professor of Chemistry Patrick Walsh; and Spencer Dreher, Head of the Process Chemistry Automation Lab at Merck. Postdoctoral fellow Simon Berritt is director of the facility.

The mass-directed liquid chromatograph is a glove box-entrained assembly that houses materials for purification with the absence of air and water. Its implementation will further improve the reaction efficiency the lab is renowned for by reducing the amount of time required for researchers to build large libraries of compounds. This will enable them to explore larger portions of chemical space with regard to biological problems. Additional ligands can also be examined more rapidly in order to invent reactions that were never before possible. The benefit of this is two-fold: The catalytic process is both more environmentally sustainable and more cost efficient, due to the fact that only one percent of a catalyst, versus 100 percent of a complex reagent, is depleted.

The second piece of equipment, the ultra-performance liquid chromatograph, is a system that will give researchers the ability to effect separations and identify the resulting compounds via mass spectrometry, which leads to superior resolving power.

The new technology facilitates improved research capabilities between the University and Merck scientists as well. “It starts with a visit to the chemists in the Merck lab to find out what kinds of deficiencies we have in our current chemistry methodologies, things that we know would be helpful in making drug-like molecules,” says Spencer Dreher. “I then feed that information back to Penn investigators, who utilize these kinds of high-tech equipment to expedite the academic research process. It’s a win-win.”