All Platinum(II) Ions Are Equal, but Some React Differently: Insights Into the Biomolecular Reactivity of Platinum(II)‐Based Anticancer Agents

Figures

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  SCHEME 1. Structure of the platinum(II) complexes involved in the current study.

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  FIGURE 1. Time‐resolved deconvoluted HR‐ESI mass spectra for the incubation reaction of 1 with 8mer (3:1).

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  SCHEME 2. Proposed mechanism for the reaction of Compound 1 (above) and Compound 2 (below) with the oligonucleotide 8mer.

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  FIGURE 2. Time‐resolved deconvoluted HR‐ESI mass spectra for the incubation reaction of 2 with 8mer (3:1).

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  FIGURE 3. Time‐resolved deconvoluted HR‐ESI mass spectra for the incubation reaction of 2 with AT1 (3:1).

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  FIGURE 4. Time‐resolved deconvoluted HR‐ESI mass spectra for the incubation reaction of 1 with CytC at room temperature.

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  FIGURE 5. Time‐resolved deconvoluted HR‐ESI mass spectra for the incubation reaction of 2 with CytC at room temperature.

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  SCHEME 3. Reaction mechanism leading to the formation of mono‐platinated adducts for Compounds 1 (top) and 2 (bottom). A similar mechanism likely applies also for additional platinum units.

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  FIGURE 6. Fragmentation map of the peak (a) at m/z 526 ([8mer + Pt(NH3)2]5−), (b) at m/z 678 ([8mer + Pt(DACH) + H]4−), (c) at m/z 566 ([8mer + Pt(Butene‐ASA)]5-) for Compound 1, and (d) Compound 2. Platinated fragments are highlighted in orange, and platinated fragments detected applying a threshold of 0.5% in the setting of the Aom2S are highlighted in yellow.

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  FIGURE 7. Fragmentation map of the peak at m/z 953 ([8mer + 2 Pt(NH3)2]3−) (left) and of the peak at m/z 756 ([8mer + 2 Pt(DACH) ‐ H]4−) (right). Mono‐platinated fragments are highlighted in orange, and di‐platinated fragments are highlighted in fuchsia.

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  FIGURE 8. Fragmentation map of the peak at (a) m/z 535 ([AT1 + Pt(DACH) + H]3+), (b) m/z 898 ([AT1 + Pt(Butene‐ASA)Cl2 + 2 H]2+) from the reaction of AT1 with Compound 1, (c) m/z 880 ([AT1 + Pt(Butene‐ASA)Cl + H]2+) from the reaction of AT1 with Compound 1, and (d) m/z 880 ([AT1 + Pt(Butene‐ASA)Cl + H]2+) from the reaction of AT1 with Compound 2.

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  FIGURE 9. Proposed model for the coordination of platinum in the adduct [AT1 + PT(DACH)]2+. The [Pt(DACH)] unit was constructed onto AT1 based on PDB structure 1N9U, followed by geometry preoptimization using the UFF force field.