Two novel sterically hindered cisplatin derivatives with the ligand L=NH 2 C(CH 2 CH 2 COOH) 3 were prepared: cis-PtCl 2 L 2 and cis-PtCl 2 L(NH 3 ). The starting compound for the syntheses was NH 2 C(CH 2 CH 2 COOtBu) 3 , also known as a building block for dendrimers. cis-PtCl 2 L 2 was prepared from K 2 PtCl 4 in an unusual two-phase reaction in water–chloroform, followed by deprotection of the tert-butyl protective groups with formic acid to yield a water-soluble complex. The mixed-ligand compound cis-PtCl 2 L(NH 3 ) was prepared from [PPh 4 ][PtCl 3 (NH 3 )] in methanol, with subsequent deprotection in formic acid. DNA-binding properties of the two compounds were investigated using the model base guanosine-5′-monophosphate (5′-GMP) and pBR322 plasmid DNA. While cisplatin [cis-PtCl 2 (NH 3 ) 2 ] induced an unwinding of 12° in pBR322 plasmid DNA, cis-PtCl 2 L(NH 3 ) induced only 3° unwinding, which is indicative of a monofunctional binding mode. Remarkably, cis-PtCl 2 L 2 did not induce any distortion in plasmid DNA, which strongly suggests that the compound does not bind to DNA. Test reactions with 5′-GMP, monitored by 1 H and 195 Pt NMR, confirmed that cis-PtCl 2 L 2 is unable to bind to DNA, whereas cis-PtCl 2 L(NH 3 ) binds only one nucleotide. Apparently, binding of platinum to nucleotides at the coordination site cis with respect to the ligand L is prevented by steric crowding. Thus, cis-PtCl 2 L(NH 3 ) must bind DNA monofunctionally at the trans position. Besides, both compounds have a chloride replaced by one of the carboxylate arms, forming a a seven-membered chelate ring. In theory, cis-PtCl 2 L 2 could also form a second chelate ring, but this was not observed.