52nd International Chemistry Olympiad, Istanbul, TURKEY Preparatory problems: THEORETICAL Problem 14. Platinum Complexes as Anticancer Drugs Medicinal inorganic chemistry based on metal‐based drugs is broadly defined as the area of research related to metal ions and metal complexes and their clinical applications. It is a new research area that developed from the discovery of the anticancer agent cisplatin. Cisplatin, cisdiamminedichloroplatinum(II), is a yellow powder and an anticancer drug widely used in the treatment of a variety of tumors, especially those of the testes, ovaries, head, and neck. The synthesis of cisplatin starts with K2[PtCl4], but has undergone several improvements since it was published more than 100 years ago. The main problem is the occurrence of impurities and the formation of the by-product trans-platin. Nowadays, the synthetic routes are mostly based on a method published in the 1970s by Dhara. In the initial step, K2[PtCl4] is reacted with excess KI, and the platinum complex is converted into the iodo analogue (A). Subsequently, NH3 is added to the compound A and compound B is formed by ligand exchange in which two NH3 ligands are exchanged with two iodo ligands. B is a yellow solid that is filtered, dried, and mixed with the aqueous solution of AgNO3. The insoluble AgI can be filtered off and cisdiamminediaquaplatinum(II) nitrate (C) is formed; then excess KCl is added to the solution of C to yield cisplatin (D). The success of the synthesis relies on the strong trans effect of the iodo ligands. The spectator ligands T that are trans to the leaving group in square-planar complexes influence the rate of substitution. This phenomenon is called the trans effect. Key point is that a strong σ-donor ligand or π-acceptor ligand greatly accelerates substitution of a ligand situating in the trans position. Trans effects follow the order given below. - For a T σ -donor: OH < NH3 < Cl < Br < CN , CH3 < I < SCN < PR3, H - For a T π-acceptor: Br < I < NCS < NO2 < CN < CO, C2H4 96