PtNH32Cl2

Pt(NH3)2Cl2, commonly known as cisplatin, is a square‑planar platinum(II) complex. The molecule features a platinum center coordinated to two ammine ligands (NH3) and two chloride ligands (Cl−) in a cis arrangement. The complex is neutral and belongs to the class of square-planar d8 Pt(II) coordination compounds.

Synthesis and isomerism: Cisplatin is typically prepared by reacting a platinum(II) chloride source, such as K2PtCl6 or K2PtCl4, with ammonia under controlled conditions to promote the cis configuration. The trans isomer, trans-[Pt(NH3)2Cl2], can form under certain conditions but exhibits little anticancer activity, highlighting the importance of geometry for biological effect.

Reactivity and speciation: In aqueous environments, chloride ligands can be displaced by water, forming aquated species that are more reactive toward DNA nucleophiles. This aquation is a key step enabling covalent binding to DNA bases, particularly the N7 position of guanine.

Biological activity and mechanism: Cisplatin is used to treat a range of solid tumors, including testicular, ovarian, bladder, lung, and head and neck cancers. Its cytotoxic effect arises from covalent binding of platinum to DNA, forming intra‑ and interstrand crosslinks (notably 1,2‑intrastrand crosslinks between adjacent guanines), which disrupt replication and transcription and trigger apoptosis. Drug resistance and toxicity limit its effectiveness.

Clinical considerations: Common adverse effects include nephrotoxicity, neurotoxicity, ototoxicity, nausea, and electrolyte disturbances. Hydration and dosing adjustments help mitigate kidney toxicity; protective agents may be employed in certain regimens. Cisplatin’s success spurred the development of later platinum drugs such as carboplatin and oxaliplatin, expanding the platinum-based chemotherapy era.

History: Cisplatin was discovered in the 1960s by Barnett Rosenberg and colleagues, with clinical approval in the late 1970s, marking a milestone in cancer therapy.