The article "Metals in Cancer Research: Beyond Platinum Metalloids" by Angela Casini and Alexander Pöthig explores the advancements in the design and synthesis of anticancer metalloids, particularly organometallic compounds. The authors highlight the unique modes of action (MoA) of these compounds, which often involve noncovalent interactions with pharmacological targets and catalytic reactions within cancer cells. They discuss the advantages of using organometallics to control the reactivity and stability of metallodrugs in physiological environments, enhancing their therapeutic efficacy and reducing side effects. Key points include: 1. **Noncovalent Organometallic Binders**: Organometallic compounds can bind to targets through noncovalent interactions, such as electrostatic, hydrophobic, π-π, and H-bonding, which are crucial for their anticancer properties. Examples include Ru(II) complexes as kinase inhibitors and Pt(II) complexes that bind to vimentin, a protein involved in epithelial-mesenchymal transition. 2. **Catalysis in Cells**: Organometallic compounds can catalyze various reactions, such as transfer hydrogenation (TH) and cross-coupling, which can be used to modulate cellular processes and enhance drug efficacy. Ru(II) and Au(III) complexes have been studied for their catalytic activities in cancer cells. 3. **Supramolecular approaches**: The use of supramolecular chemistry, such as self-assembly, to create nanostructures with diverse topologies and functionalizability is discussed. This approach can lead to controlled release of active species and enhanced targeting of cancer cells. 4. **Challenges and Future Directions**: The authors identify the importance of understanding the microenvironmental factors that influence the reactivity of metallodrugs, emphasizing the need for new chemical guidelines to predict and control their behavior in biological systems. Overall, the article provides a comprehensive overview of the latest trends and strategies in the development of anticancer metallodrugs, highlighting the potential of organometallic compounds to revolutionize cancer therapy.The article "Metals in Cancer Research: Beyond Platinum Metalloids" by Angela Casini and Alexander Pöthig explores the advancements in the design and synthesis of anticancer metalloids, particularly organometallic compounds. The authors highlight the unique modes of action (MoA) of these compounds, which often involve noncovalent interactions with pharmacological targets and catalytic reactions within cancer cells. They discuss the advantages of using organometallics to control the reactivity and stability of metallodrugs in physiological environments, enhancing their therapeutic efficacy and reducing side effects. Key points include: 1. **Noncovalent Organometallic Binders**: Organometallic compounds can bind to targets through noncovalent interactions, such as electrostatic, hydrophobic, π-π, and H-bonding, which are crucial for their anticancer properties. Examples include Ru(II) complexes as kinase inhibitors and Pt(II) complexes that bind to vimentin, a protein involved in epithelial-mesenchymal transition. 2. **Catalysis in Cells**: Organometallic compounds can catalyze various reactions, such as transfer hydrogenation (TH) and cross-coupling, which can be used to modulate cellular processes and enhance drug efficacy. Ru(II) and Au(III) complexes have been studied for their catalytic activities in cancer cells. 3. **Supramolecular approaches**: The use of supramolecular chemistry, such as self-assembly, to create nanostructures with diverse topologies and functionalizability is discussed. This approach can lead to controlled release of active species and enhanced targeting of cancer cells. 4. **Challenges and Future Directions**: The authors identify the importance of understanding the microenvironmental factors that influence the reactivity of metallodrugs, emphasizing the need for new chemical guidelines to predict and control their behavior in biological systems. Overall, the article provides a comprehensive overview of the latest trends and strategies in the development of anticancer metallodrugs, highlighting the potential of organometallic compounds to revolutionize cancer therapy.