Cisplatin
Properties
| State | Solid |
| Color | Yellow |
| Solubility | Slightly soluble in water (2.5 g/L); soluble in DMF and DMSO |
| Melting Point | 270 °C (decomposes) |
About Cisplatin
Cisplatin is a square-planar Pt(II) d⁸ complex where the geometry of two ammine and two chloride ligands at 90° to each other is the entire reason the molecule cures testicular cancer and the trans isomer doesn't. Inside a cell, the chloride ligands hydrolyze (the cytoplasmic [Cl⁻] of ~4 mM is far below the 100 mM blood plasma level that keeps the prodrug intact in the bloodstream) to give cis-[Pt(NH3)2(H2O)2]²⁺, which then reacts with N7 of guanine in DNA. Because the two reactive Pt sites are cis, the platinum bridges two adjacent guanines on the same strand, almost always in 5'-GG-3' or 5'-AG-3' contexts — the 1,2-intrastrand crosslink kinks the helix by about 35–40°, displaces the minor groove, and recruits HMG-domain proteins that block lesion bypass and trigger apoptosis. Transplatin can't form the same lesion because its leaving groups are 180° apart. Barnett Rosenberg discovered the activity in 1965 by accident: he was running an experiment with platinum electrodes in NH4Cl-buffered E. coli culture and noticed the bacteria stopped dividing but kept elongating into filaments. The platinum was etching off the electrodes and forming cis-[Pt(NH3)2Cl2] in situ — a tiny amount, but enough to inhibit cell division. FDA approval came in 1978, and cisplatin combination therapy still cures over 95% of testicular cancer cases that have not metastasized to brain. Carboplatin (1989) and oxaliplatin (2002) are second- and third-generation analogs designed to reduce the nephrotoxicity that limits cisplatin dosing.
Where you'll encounter it
If you walk into an oncology pharmacy compounding room, cisplatin is one of the cytotoxics you'll see being prepared in a Class II Type B2 biosafety cabinet, because aerosolized platinum compounds cross skin and trigger severe sensitization. Bench biochemists use it as the standard 'kink-the-DNA' tool for studying nucleotide-excision-repair machinery, XPA recognition, and HMGB1 binding. In coordination-chemistry labs it's still the textbook example for explaining the trans effect — the chloride ligands have a much higher trans-influence than ammonia, which is why the synthesis from K2[PtCl4] proceeds cleanly to the cis isomer if you start by adding NH3 first.
Common Uses
- First-line chemotherapy for non-seminomatous testicular germ-cell tumors via BEP regimen (bleomycin/etoposide/cisplatin)
- Induction therapy for advanced ovarian, bladder, and head-and-neck squamous-cell carcinomas in combination protocols
- Concurrent chemoradiotherapy for cervical and nasopharyngeal carcinoma to enhance radiosensitization
- Reference compound for benchmarking new platinum-based antitumor agent development in medicinal inorganic chemistry
- Mechanistic probe for studying nucleotide-excision-repair (NER) pathway recognition of bulky DNA adducts
- Substrate for HMGB1 and XPA protein-binding assays that probe lesion-recognition specificity
- Teaching example for the trans-effect ordering and isomer-selective synthesis from K2[PtCl4]
- Component of intraperitoneal chemotherapy regimens for ovarian cancer following cytoreductive surgery
Safety Information
Cytotoxic chemotherapy drug — handle only in negative-pressure compounding pharmacies with HEPA-filtered Class II BSCs and chemo-rated PPE per USP 800. NIOSH lists it on the Hazardous Drug List (Group 1: antineoplastic). GHS H300+H310+H330 (fatal by oral, dermal, and inhalation routes), H340 (mutagenic), H350 (carcinogenic, IARC Group 2A 'probably carcinogenic to humans'), H360 (reproductive toxicity), H372 (kidney damage). Dose-limiting clinical toxicities are nephrotoxicity (proximal-tubule damage starting around 50 mg/m²), peripheral neuropathy (cumulative-dose-dependent above 300 mg/m²), and ototoxicity (irreversible high-frequency hearing loss). Spill response: use chemo-spill kit; chlorine-bleach inactivation is contraindicated because bleach can release toxic platinum species. Standard protocol is sodium thiosulfate decontamination, which reduces Pt(II) to less reactive thiosulfate complexes.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.