Orthogonal Linking of Gemcitabine by Acyclovir and Bortezomib: A Rational Chemistry Laboratory Introduction of Both Noncovalent and Covalent Dynamics

Abstract

Constitutional dynamic chemistry (CDC), as defined by Lehn ( Chem. Soc. Rev. 2007, 36, 151−160), covers both supramolecular science and dynamic covalent chemistry to process components recombination toward the chemistry of complex matter. While CDC has increasingly guided active research decisions during the past decades, undergraduate chemistry curricula do not reflect the prevalence of such concepts and knowledge; this article seeks to introduce such ideas to laboratory practice. Incorporation of CDC and its characterization techniques, such as ¹H NMR and mass spectrometry (MS), into chemistry education is warranted to support CDC-relevant learning experiences, understanding of spectroscopy instrumentation, and student motivation to pursue a professional career. Herein, we develop an experimental design by combining supramolecular forces, i.e., H-bonding interaction, and dynamic covalent linkage, i.e., borate ester bond, toward orthogonal linking of the chemotherapeutic agent gemcitabine (GEM) by the antiviral drug acyclovir (ACV) and proteasome inhibitor bortezomib (BTZ). Such design enables a “double dynamic” process, which leverages both noncovalent and covalent dynamics. Moreover, this laboratory program outlines how NMR and MS technologies are employed to characterize H-bonding association and boronic ester bonds. Such a lab experiment provides the prospect for instructors to illustrate to undergraduates with a basic background in chemistry and medical science the state-of-the-art H-bonding interaction and boronic ester bond, modern characterization instruments, and broad impacts of CDC.