Binuclear monofunctional platinum(II) complexes formed by hexaazamacrocyclic bisdien ligands: Crystal structure, DNA binding and cytotoxicity studies

Two binuclear 3N-chelated monofunctional PtII complexes, [Pt2L1Cl2]Cl2 (complex III) and [Pt2L2Cl2]Cl2 (complex IV) [L1 = 3,6,9,16,19,22-hexaazatricyclo[22.2.2.211,14]-triaconta-11,13,24,26(1),27,29-hexaene, L2 = 3,6,9,17,20,23-hexaazatricyclo[23.3.1.111,15]-triaconta-1(29),11(30),12,14,25,27-hexaene] have been synthesized and structurally characterized. Structural determination revealed that each PtII center was coordinated by one chloride anion and three N atoms from each diethylenediamine motif. The Pt–Cl bonds in complex III are shorter than those found in complex IV. The rigid para- and meta-xylylene groups make the two complexes adopt a rigid boat-like conformation and a flexible twisted chair-like conformation, respectively. Moreover, complex III has higher tendency to bind with each other than complex IV. DNA binding studies demonstrated that complex IV could bind effectively with calf thymus DNA, possibly via platination of N7 of guanine residue, while no obvious DNA binding was observed for complex III. However, complex III displays a comparable cytotoxicity to cisplatin against HeLa cell line, while compound IV does not show any effective cell inhibition at low concentration. Therefore, the rigid spacers in complexes III and IV play a determining role in their anti-cancer activity and DNA binding ability.

Graphical abstractBinuclear PtII complexes formed by para- and meta-xylylene spaced cyclic bisdiens display different cytotoxicity and DNA binding behavior. The rigid spacers in the complexes play a determining role in their anti-cancer activity and DNA binding ability.Figure optionsDownload full-size imageDownload as PowerPoint slide