Boron-containing compounds have recently emerged as useful biologically active substances with unique mechanisms of action. This proposal describes a program in synthetic chemistry geared toward developing boron-nitrogen-containing heterocycles (BN heterocycles) for use in biomedical research. Specifically, we are interested in 1,2-azaborine heterocycles, which are aromatic compounds isosteric with arenes. The broad utility and fundamental importance of arenes combined with the unique elemental and chemical features of boron make 1,2-azaborines attractive targets for biomedical investigations. Potential benefits of research into boron-based drugs include discovery of novel boron-specific mechanisms of biological activity that are unattainable by conventional organic molecules and attenuated development of drug resistance by targeted pathogens. We outline a synthetic program for the preparation of 1,2-azaborine derivatives, a physical organic program that uses a combined synthetic, structural, spectroscopic, and computational approach to address the aromaticity and reactivity of 1,2-azaborines, and a chemical biology program to establish the reactivity and interactions of BN heterocycles in a biological environment. Our proposed studies will enhance the fundamental understanding of the structure, bonding, and aromaticity the 1,2-azaborine heterocycle and illuminate the changes in the properties of classic aromatic organic molecules (e.g., benzene and indole) upon the replacement of a C=C bond with the isostructural inorganic B-N unit. The basic science resulting from the proposed work will bring new impetus to the chemistry of novel aromatics while at the same time promote the design and development of new boron-derived biologically active compounds with improved pharmacological profiles and new mechanistic tools for chemical biology.