The complex-in-a-complex cation [Pt(acac)2⊂(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)subset of(p-cym)(6)Ru-6(tpt)(2)(dhnq)(3)](6+) ([Pt(acac)(2)subset of 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)subset of 1](6+), its empty counterpart [1](6+) and the previously reported smaller complex-in-a-complex cation [Pt(acac)(2)subset of(p-cym)(6)Ru-6(tpt)(2)(dhbq)(3)](6+) ([Pt(acac)(2)subset of 2](6+)) were described. The reactivity of [Pt(acac)(2)subset of 1](6+) towards amino acids and the degradation products formed were similar to those observed with [1](6+) and [Pt(acac)(2)subset of 2](6+) but the kinetic of the reactions was much slower. Interestingly, [Pt(acac)(2)subset of 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)subset of 2](6+). Unlike [Pt(acac)(2)subset of 2](6+) and as observed previously with [1](6+), [Pt(acac)(2)subset of 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)subset of 1](6+) and [1](6+). In solution, [Pt(acac)(2)subset of 1](6+) disassembles at a lower rate than [Pt(acac)(2)subset of 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)subset of 1](6+) in the blood is probably sufficiently long to enter cells and reach the target intact. (C) 2017 Elsevier B.V. All rights reserved.