1083165-48-3Relevant academic research and scientific papers
Design, synthesis, characterisation and chemical reactivity of mixed-ligand platinum(ii) oxadiazoline complexes with potential cytotoxic properties
Wagner, Gabriele,Marchant, Anthony,Sayer, James
, p. 7747 - 7759 (2010/10/04)
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){NC(Ph)-O- N(Me)-CR1R2}] from which the remaining nitrile can be replaced by 7-NO2TAA. The resulting complexes trans-[PtX 2(7-NO2TAA) {NC(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-NO 2TAA 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. The Royal Society of Chemistry 2010.
Synthesis and characterisation of mixed ligand Pt(ii) and Pt(iv) oxadiazoline complexes
Sarju, Julien,Arbour, Jannine,Sayer, James,Rohrmoser, Benjamin,Scherer, Wolfgang,Wagner, Gabriele
, p. 5302 - 5312 (2009/02/06)
The nitrile ligands in trans-[PtX2(PhCN)2] (X = Cl, Br, I) undergo sequential 1,3 dipolar cycloadditions with nitrones R 1R2C=N+(Me)-O- (R1 = H, R2 = Ph; R1 = CO2Et, R2 = CH 2CO2Et) to selectively form the Δ4-1,2,4- oxadiazoline complexes trans-[PtX2(PhCN) {N=C(Ph)-O-N(Me)-CR 1R2}] or trans-[PtX2{N=C(Ph)-O-N(Me)-CR 1R2}2] in high yields. The reactivity of the mixed ligand complexes trans-[PtX2(PhCN){N=C(Ph)-O-N(Me)-CR 1R2}] towards oxidation and ligand substitution was studied in more detail. Oxidation with Cl2 or Br2 provides the Pt(iv) species trans-[PtX2Y2(PhCN){N=C(Ph)-O-N(Me)- CH(Ph)}] (X, Y = Cl, Br). The mixed halide complex (X = Cl, Y = Br) undergoes halide scrambling in solution to form trans-[PtX(4-n)Y n(PhCN){N=C(Ph)-O-N(Me)-CH(Ph)}] as a statistical mixture. Ligand substitution in trans-[PtCl2(PhCN){N=C(Ph)-O-N(Me)-CR 1R2}] allows for selective replacement of the coordinated nitrile by nitrogen heterocycles such as pyridine, DMAP or 1-benzyl-2- methylimidazole to produce mixed ligand Pt(ii) complexes of the type trans- [PtX2(heterocycle){N=C(Ph)-O-N(Me)-CR1R2}]. All compounds were characterised by elemental analysis, mass spectrometry, IR and 1H, 13C and 195Pt NMR spectroscopy. Single-crystal X-ray structural analysis of (R,S)-trans-[PtBr 2{N=C(Ph)-O-N(Me)-CH(Ph)}2] and trans-[PtCl 2(C5H5N){N=C(Ph)-O-N(Me)-CH(Ph)}] confirms the molecular structure and the trans configuration of the heterocycles relative to each other. The Royal Society of Chemistry.
