A new approach to the synthesis of novel bifunctional dinuclear platinum complexes with linear coordinating spermidine and spermine is reported. The synthetic pathway involves first the three-step selective protection of the polyamines, giving bis(trifluoroacetyl)polyamines (1, 4), (tert-butoxycarbonyl)bis(trifluoroacetyl)polyamines (2, 5), and (tert-butoxycarbonyl)polyamines (3, 6), respectively. The platination at desired sites with activated species of cis- or trans-[PtCl2(NH3)2] (CDDP or TDDP, respectively) produces the BOC-protected dinuclear species [{cis- or trans-PtCl(NH3)2}2(μ-L)]X (7, L = BOC-spermidine, X = (NO3)0.75Cl1.25; 9, L = (BOC)2-spermine, X = Cl2; cis spermine species not isolated). Through final deprotection, three different complexes were obtained and further investigated:  [{trans-PtCl(NH3)2}2{μ-spermidine-N 1,N 8}]Cl3 (8), [{trans-PtCl(NH3)2}2{μ-spermine-N 1,N 12}]Cl4 (10), and [{cis-PtCl(NH3)2}2{μ-spermine-N 1,N 12}]Cl4 (11). One- and two-dimensional NMR solution studies provided evidence that 11, at physiological pH, forms an inert bis((tetraamine)platinum) species in which each Pt is chelated by a central and a terminal amino group. In contrast, complexes 8 and 10 retain their reactivity, showing only reversible formation of hydroxo bridges. The comparison of in vitro cytotoxicity data for 8, 10, and 11 with data for previously described bifunctional dinuclear complexes shows the enhanced activity particularly of complex 8 in the CDDP-resistant L1210 cell line. The binding of 8 and 10 to poly(dG-dC)·poly(dG-dC) is further increased and also reflected by B → Z conformational changes at lower doses.

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The formation and X-ray structure of a cyclic, tetranuclear Ptll complex of composition [ { P t ( e n ) ( ~H ) ) -~] ( N 0 ~) ~ (uH = uracil monoanion) and its conversion into cyclic, octanuclear derivatives is reported.

The introduction of the malonate ligand as a leaving group in trifunctional dinuclear platinum complexes allows stepwise binding modes to be controlled, as shown using a small mononucleotides such as guanosine 5‘-monophosphate. Subtle changes in the metal coordination sphere can be used to produce specific and selective ternary DNA−DNA and DNA−protein interactions.

Je nach Konfiguration der Metalleinheit (cis oder trans) sowie in Abhängigkeit von der Reihenfolge der Koordination entstehen mit den Sechsring‐Heterocyclen Uracil, 1‐Methylcytosin und 2‐Aminopyridin Komplexe mit unterschiedlichen Topologien: offene Schachtel, Rechteck bzw. Sechseck (siehe unten). Diese Komplexe enthalten sechs oder acht Metalleinheiten (mit PtII, NiII, PdII, CuII, AgI; als Kugeln dargestellt) in ungewöhnlicher relativer Anordnung.