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Issue 33, 2010
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Design, synthesis, characterisation and chemical reactivity of mixed-ligand platinum(II) oxadiazoline complexes with potential cytotoxic properties

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Abstract

A series of mixed ligand platinum(II) oxadiazoline complexes bearing 7-nitro-1,3,5-triazaadamantane (7-NO2TAA) as a labile and reactive nitrogen ligand has been synthesised from easily accessible starting materials. [2+3] cycloaddition of nitrones R1R2C–N+(Me)O to only one of the nitrile ligands in trans-[PtX2(PhCN)2] (X = Cl, Br) results in the selective formation of mono-oxadiazoline complexes trans-[PtX2(PhCN){N[double bond, length as m-dash]C(Ph)–O–N(Me)–CR1R2}] from which the remaining nitrile can be replaced by 7-NO2TAA. The resulting complexes trans-[PtX2(7-NO2TAA) {N[double bond, length as m-dash]C(Ph)–O–N(Me)–CR1R2}] and their precursors were characterised by elemental analysis, IR and multinuclear NMR spectroscopy.

The suitability of the target complexes as anticancer agents was extrapolated from their general chemical reactivity. They are stable in DMSO, but react with thiols and undergo aquation of a chloro ligand. In the absence of a competing ligand, the coordinated 7-NO2TAA ligand slowly hydrolyses in an aqueous medium under release of formaldehyde, and this could induce bioactivity independent of the one typically found with platinum compounds. With nitrogen heterocycles such as pyridine a slow exchange of the 7-NO2TAA ligand occurs. A combined DFT/AIM study confirms the reaction observed in the experiment and predicts that other nitrogen heterocycles such as DNA nucleobases should react in the same way. Moreover, the 7-NO2TAA should be even more labile in an aqueous medium where protonation of the remaining amines can occur. A PM6 molecular modelling study suggests that the PtCl(oxadiazoline) fragment formed after release of one chloro and the labile 7-NO2TAA ligand fits well into the DNA groove and is able to form d(GpG) intrastrand crosslinks similar to the ones observed with cisplatin.

Graphical abstract: Design, synthesis, characterisation and chemical reactivity of mixed-ligand platinum(ii) oxadiazoline complexes with potential cytotoxic properties

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Publication details

The article was received on 22 Apr 2010, accepted on 07 Jun 2010 and first published on 26 Jul 2010


Article type: Paper
DOI: 10.1039/C0DT00360C
Citation: Dalton Trans., 2010,39, 7747-7759
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    Design, synthesis, characterisation and chemical reactivity of mixed-ligand platinum(II) oxadiazoline complexes with potential cytotoxic properties

    G. Wagner, A. Marchant and J. Sayer, Dalton Trans., 2010, 39, 7747
    DOI: 10.1039/C0DT00360C

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