Non‐Medical Applications of Inorganic Medicines. A Switch Based on Mechanistic Knowledge

• Published in: Chemistry : a European journal Vol. 30; no. 60; pp. e202402647 - n/a
• Main Authors: Cirri, Damiano, Di Leo, Riccardo, Chiaverini, Lorenzo, Tolbatov, Iogann, Marrone, Alessandro, Messori, Luigi, Pratesi, Alessandro, La Mendola, Diego, Marzo, Tiziano
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 28.10.2024
• Subjects: Amino acids; Arsenic; Arsenic compounds; Biological effects; Cancer; Catalytic converters; Crystallography; Drug interaction; Drug repurposing; Drugs; Heavy metals; Lysozyme; Mass spectrometry; Metallodrugs; Molecular interactions; Palladium; Protein structure; Proteins; X-ray crystallography; X-ray crystallography; Drug repurposing; Mass spectrometry; Metallodrugs; Cancer
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202402647

Metals have been used in medicine for centuries. However, it was not until much later that the effects of inorganic drugs could be rationalized from a mechanistic point of view. Today, thanks to the technologies available, this approach has been functionally developed and implemented. It has been found that there is probably no single biological target for the pharmacological effects of most inorganic drugs. Herein, we present an overview of some integrated and multi‐technique approaches to elucidate the molecular interactions underlying the biological effects of metallodrugs. On this premise, selected examples are used to illustrate how the information obtained on metal‐based drugs and their respective mechanisms can become relevant for applications in fields other than medicine. For example, some well‐known metallodrugs, which have been shown to bind specific amino acid residues of proteins, can be used to solve problems related to protein structure elucidation in crystallographic studies. Diruthenium tetraacetate can be used to catalyze the conversion of hydroxylamines to nitrones with a high selectivity when bound to lysozyme. Finally, a case study is presented in which an unprecedented palladium/arsenic‐mediated catalytic cycle for nitrile hydration was discovered thanks to previous studies on the solution chemistry of the anticancer compound arsenoplatin‐1 (AP‐1). Starting from the description of integrated approaches for unveiling the molecular interactions underlying the biological effects of metallodrugs, through selected examples, it is highlighted how the obtained mechanistic information may turn relevant for the application of inorganic drugs in fields different from medicine.