The complex-in-a-complex cation [Pt(acac)2Ì(p-cym)6Ru6(tpt)2(dhnq)3]6+: Its stability towards biological ligands

The reactivity of the highly cytotoxic complex-in-a-complex cation [Pt(acac)2 (pcym)6Ru6(tpt)2(dhnq)3]6+ ([Pt(acac)2 1]6+) towards amino acids, proteins, nucleotides and an oligonucleotide was investigated by NMR, MS, UV/Vis and CD experiments. The similarities and differences between the metallaprism [Pt(acac)2 1]6+, its empty counterpart [1]6+ and the previously reported smaller complex-in-a-complex cation [Pt(acac)2 (p-cym)6Ru6(tpt)2(dhbq)3]6+ ([Pt(acac)2 2]6+) were described. The reactivity of [Pt(acac)2 1]6+ towards amino acids and the degradation products formed were similar to those observed with [1]6+ and [Pt(acac)2 2]6+ but the kinetic of the reactions was much slower. Interestingly, [Pt(acac)2 1]6+ imposed stronger structural effects on the human proteins HsA, Tf, Mb, Cyt c, and Ub compared to the empty metallaprism [1]6+. The effects were similar to those of [Pt(acac)2 2]6+. Unlike [Pt(acac)2 2]6+ and as observed previously with [1]6+, [Pt(acac)2 1]6+ did not react with nucleotides. However, similar interactions with a double stranded oligonucleotide were observed in the presence of both metallaprisms [Pt(acac)2 1]6+ and [1]6+. In solution, [Pt(acac)2 1]6+ disassembles at a lower rate than [Pt(acac)2 2]6+. Overall, the results show that the enhanced stability of [1]6+ is kept when a guest is trapped inside the hydrophobic cavity, suggesting that the half-life of [Pt(acac)2 1]6+ in the blood is probably sufficiently long to enter cells and reach the target intact.