cis-[PtCl2(NH3)2] is the anticancer drug cisplatin, but the iodide analogue cis-[PtI2(NH3)2] is inactive. This inactivity is usually attributed to the greater stability and lower reactivity of Pt−I bonds compared to Pt−Cl in aqueous solution. Interest in reactions of Pt(IV) complexes with thiols arises from the reductive activation of Pt(IV) anticancer drugs in blood plasma. Recently, we found (J. Am. Chem. Soc. 1998, 120, 8253−8254) that low M r thiols react with Pt(IV)−I bonds of trans,cis-[Pt(en)(OH)2I2] via attack on the coordinated iodo ligand giving rise to reactive chelate-ring-opened Pt(II) ethylenediamine species. Here we report reactions of the Pt(II) and Pt(IV) complexes [Pt(en)I2] and trans,cis-[Pt(en)(OH)2I2] with the major thiol in blood plasma, Cys34 of the protein albumin (66 kDa). Unexpectedly, [Pt(en)I2] reacted more rapidly with albumin than the cisplatin analogue, [Pt(en)Cl2], and did not give products with Pt bound to Cys34. The Pt(IV) chloro analogue, trans,cis-[Pt(en)(OH)2Cl2], did not react at all with albumin. Reactions of trans,cis-[Pt(en)(OH)2I2] with the protein, via direct attack of an iodo ligand on Cys34, gave rise to a relatively stable sulfenic acid derivative, in contrast to reactions with low M r thiols. Reactions of Pt complexes with thiols in proteins can therefore take a different course:  albumin can exert control over the reactivity of Cys34 and stabilize activated derivatives such as the sulfenyl iodide and sulfenic acid. The reactivity of iodide ligands in Pt complexes is much higher than has been previously recognized, and it may be possible to incorporate them into drug design strategies.

Both oxidized and reduced glutathione (gamma-L-Glu-L-Cys-Gly) react with the anticancer complex [Pt(en)Cl(2)] to form the bicyclic complex illustrated (en=ethylenediamine). This unprecedented structure, which was determined from extensive NMR experiments, contains a ten-membered macrochelate ring.

The determination of Pt by ICP-MS in environmental and biological samples is well documented and generally performed after dissolution in dilute HNO 3.On the other hand, I is poorly ionised in the plasma and, at low pH, memory effects and instability arise from the formation of potentially volatile species, such as I 2 and HI, depending on the oxidation state of I. In order to investigate the role of iodo ligands in the design of Pt anticancer complexes, we have optimised conditions for the simultaneous determination of Pt and I. Standards and samples were diluted in 10 mM KOH and improved ion extraction into the quadrupole was achieved by means of an additional pump (S-Option@), leading to about a 2-fold increased sensitivity. The limits of detection in water were 10 and 0.6 ng l−1 for I and Pt, respectively, but increased to 23 ng l−1 for I and 2.2 ng l−1for Pt in KOH (10 mM ). The analysis of certified reference materials yielded the following results: 0.84±0.05 mg g−1 I (certified value: 0.81±0.05 mg g−1) in BCR CRM 063R 'Skimmed Milk Powder', and 0.121±0.006 mg ml−1 Pt (indicative value: 0.12 mg ml−1) in NIST SRM 2670 'Toxic Metals in Urine'. Pt5I ratios ranging from 0.240 to 1.035 were measured with an accuracy of 101.3±2.4%. The determination of the Pt5I ratio in the low M r fraction of reaction mixtures of diiodo Pt complexes and human albumin provided evidence for the release of iodide and for different kinetics for the reactions of diiodo Pt() and Pt() complexes.

Sowohl oxidiertes als auch reduziertes Glutathion (γ‐L‐Glu‐L‐Cys‐Gly) reagiert mit dem gegen Krebs wirksamen Komplex [Pt(en)Cl2] unter Bildung des abgebildeten bicyclischen Komplexes (en=Ethylendiamin). Dessen einmalige Struktur mit einem zehngliedrigen Makrochelatring wurde durch eine Kombination zahlreicher NMR‐Experimente bestimmt.