The importance of molecular structure elucidation in medicinal inorganic chemistry drug development is discussed and illustrated using three vignettes on Ru-, Au-, and As-based drugs. An outlook on Sb-based drugs is provided. The development of three classes of medicinal inorganic compounds is reviewed, highlighting the important role of structure elucidation. The progress of Ru-, Au-, and As-based compounds provide a justification for working to understand the structures of clinically used Sb-containing antiparasitic drugs.

Abstract

Structure elucidation plays a critical role across the landscape of medicinal chemistry, including medicinal inorganic chemistry. Herein, we discuss the importance of structure elucidation in drug development and then provide three vignettes that capture key instances of its relevance in the development of biologically active inorganic compounds. In the first, we describe the exploration of the biological activity of the trinuclear Ru compound called ruthenium red and the realization that this activity derived from a dinuclear impurity. We next explore the development of Au-based antitubercular and antiarthritic drugs, which features a key step whereby ligands were discovered to bind to Au through S atoms. The third exposition traces the development of As-based antiparasitic drugs, a key step of which was the realization that the reaction of arsenic acid and aniline does not produce an anilide of arsenic acid, as originally thought, but rather an amino arsonic acid. These case studies provide the motivation for an outlook in which the development of Sb-based antiparasitic drugs is described. Although antileishmanial pentavalent antimonial drugs remain in widespread use to this day, their chemical structures remain unknown.