Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs
Jon T Njardarson1, Elisa Tomat1,2
1Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona85721, United States.
Journal of Medicinal Chemistry
|July 21, 2026
Summary
This study reviews FDA-approved drugs, identifying structural motifs that bind metal ions. It highlights common and emerging bidentate coordination sites in pharmaceuticals for drug discovery and development.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Metal ion coordination is crucial for many pharmaceuticals, including chelation therapy agents and metalloprotein inhibitors.
- Unrecognized interactions with endogenous metals can affect drug efficacy and safety.
Purpose of the Study:
- To survey US FDA-approved drugs for structural motifs capable of bidentate metal ion coordination.
- To identify common and emerging metal-binding structural features in pharmaceuticals.
Main Methods:
- Systematic review of small molecules approved by the US FDA.
- Focus on identifying bidentate coordination motifs involving nitrogen, oxygen, and sulfur donors.
- Analysis of chelate ring formation (five- or six-membered).
Main Results:
- Identified well-known motifs like hydroxamic acids, catechols, and salicylic acids.
- Highlighted drugs containing 1,3-dicarbonyl motifs and related oxygen donors.
- Observed a prominent role and growth in nitrogen heterocycles as bidentate motifs.
Conclusions:
- Numerous FDA-approved drugs possess structural features for bidentate metal coordination.
- Understanding these motifs is vital for predicting drug-metal interactions and designing new therapeutics.
- Nitrogen heterocycles represent a significant and growing class of metal-binding motifs in pharmaceuticals.
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