The structurally unique macrochelate [{Pt(en)}(2)-mu-{H2N(CH2)(6)-NH2}-mu-(SG)] (I) is the principal product of the reaction of the dinuclear compound [{PtCl(en)}(2)-mu-{H2N(CH2)(6)NH2}]Cl-2 (1) with reduced glutathione (GSH) in a stoichiometric 1:1 ratio in phosphate buffered saline (PBS) (pH 7.35). The macrochelate is formed through simultaneous bridging of the hexanediamine linker and glutathione thiolate. This represents a novel structure for glutathione adducts of platinum. At higher (1:4) ratios of Pt complex to GSH, an interesting interchange between bridged Pt-(SG)-Pt and terminal Pt-SG species is observed with the diamine linker still remaining intact in all cases. The integrity of I is further evident when reaction ratios are increased to 1:4 (Pt complex/GSH), and additional minor products are identified as [{Pt(en)SG}(2)-mu-{NH2(CH2)(6)NH2}] (II), which transforms to [{Pt{NH2(CH2)(2)NH2}-(SG)}(2)-mu-{ H2N(CH2)(6)NH2}-mu-(SG)] (III), where the chelate ring is broken to produce a dangling monodentate ethylenediamine. The chemical shifts of the Pt-NH2 linker in all compounds are explained by consideration of the enhanced rigidity of the macrochelate (I) leading to shielding in comparison to the "open" monodentate structures (II, III). The remarkable stability of I is discussed in terms of possible biological implications.