Platinum(II) complexes containing long-chain hydrophobic N-alkyl-diamine ligands: Synthesis, characterization, molecular modeling, and cytotoxic activity

A series of novel platinum(II) complexes derived from N-alkyl-ethanediamine and N-alkyl-propanediamine ligands were prepared and characterized. These complexes contain a long chain aliphatic diamine where the carbon length is variable and present a hydroxyl group in two different positions. The complexes with the ethanediamine derivatives were prepared from K2PtCl4. Interestingly, the propanediamine derivatives did not react well with this platinum salt under the experimental conditions normally employed and could only be obtained from the more reactive K2PtI4. A theoretical molecular modeling study was performed to understand this difference in reactivity and it showed that the conformation around the diamine plays an important role in the ring closure step of complex formation. The complexes had their cytotoxicity investigated in B16F1, CT26, B16F10, and MDA cell lines. Some of them demonstrated superior activity when compared to cisplatin and carboplatin. We were also able to confirm a structure–activity relationship between cytotoxicity and carbon chain length. Hydrophobic complexes of ethanodiamine derivatives were prepared from K2PtCl4. Interestingly, the propanediamine derivatives did not react well with this platinum salt and could only be obtained from the more reactive K2PtI4. A theoretical molecular modeling study was performed to help understand this difference in reactivity. [Display omitted] ► Platinum diammine complexes containing long chain, hydroxy alkanes were prepared. ► Cytotoxicity has been examined in four cell lines. ► Molecular modeling study was performed to explain differences in ligand reactivity. ► Structure activity relationships are addressed.