Catalyst: Systems chemistry links reactions to molecular function

Abstract

Andrew McGrath completed his PhD studies at the University of Michigan with Tim Cernak, studying amine-acid coupling reactions and their application in medicinal chemistry. Andrew was an undergraduate of the University of Colorado at Colorado Springs and is currently a postdoctoral researcher at Merck & Co., Inc. in Rahway, NJ. Haiyan Huang is currently a postdoctoral fellow in the Cernak Lab at the University of Michigan, where she studies amine-acid coupling reactions. She earned her BSc from Sun Yat-sen University and her PhD studying total synthesis at McGill University under the supervision of Prof. Lumb. Christopher O. Audu is currently a chief resident in vascular surgery at the University of Michigan. He studied at Purdue (BSc) and Dartmouth (MD and PhD) and performed postdoctoral research with Drs. Cernak and Gallagher at the University of Michigan. He will begin an assistant professorship of vascular surgery and chemical research at the University of Utah in the fall of 2024. Tim Cernak is an associate professor of medicinal chemistry at the University of Michigan, exploring the role of data science in chemistry and medicine in biodiversity conservation. Prior to working at the University of Michigan, he worked at Merck & Co., Inc. He is a co-founder of Iambic Therapeutics.

Figure 1.. Systems chemistry unites big data packages to link available chemical building blocks to function

The output would be a functional molecule, and the data can be generated with high-throughput experimentation, if not already available, and studied with cheminformatics. The complementary field of systems biology would generally propose a therapeutic target. We define a reaction as comprising both a transformation—to map the changing of atoms and bonds—and reaction conditions—to experimentally realize the transformation.

Figure 2.. The interconnection of relevant parameters and examples where all systems chemistry parameters are considered

(A) The interplay of available data packages can suggest the invention of new chemical transformations. (B–C) This interplay has been exploited with (B) diverse amine-acid coupling reactions to modulate physicochemical properties via reaction conditions and in (C) activity-directed synthesis to modulate bioactivity via choice of catalyst.