The Gas‐Phase Chemistry of cis‐Diammineplatinum(II) Complexes: A Joint Experimental and Theoretical Study

Abstract

Prior to reactions with DNA, the anticancer drug cisplatin [Pt(II)(NH(3))(2)Cl(2)] forms a series of solvolysis intermediates by successive replacement of the chloro ligands by water or hydroxyl groups. The bonding of water to Pt(II) is weak, and it is easily substituted by donor ligands present in the solution, for example, amines or alcohols. We studied such compounds using high-resolution electrospray mass spectrometry with a linear ion trap and DFT computations. This combination allows for the first time a detailed description of the reactions initiated by the central atom of the complexes. Positively charged cisplatin adducts with primary and secondary alcohols ([Pt(II)(NH(3))(2)(ROH)Cl](+)) show unexpected reactions when fragmented in a linear ion trap. Either water loss is accompanied by formation of the corresponding carbene complex, or loss of the corresponding aldehyde/ketone leads to the formation of the complex [Pt(NH(3))(2)(H(2))Cl](+). Complete loss of the alcohol ligand is not observed for kinetic reasons. A detailed investigation by DFT and molecular dynamics for the cisplatin/methanol complex [Pt(II)(NH(3))(2)(CH(3)OH)Cl](+) allowed identification of the reaction mechanisms leading to the observed fragmentation patterns. The initial step for both fragmentation pathways is activation of the alpha-CH bond and subsequent H transfer within the complex. Direct activation of the OH or CO bond is less favorable. Ligands bound to the Pt(II) center such as the chloro ligand can directly catalyze the reaction by intermediate binding of H atoms. Upon collision activation, adducts without an alpha-H atom such as [Pt(NH(3))(2){(CH(3))(3)COH}Cl](+) show loss of water or the corresponding alkene.

Anion-π interactions—interactions between benzo-crown ether metal cation complexes and counter ions

“…At the higher cone voltages, abundant ions [NO 2 ϩ ions should be regarded as organometallic species formed as a consequence of the C-H bond activation and will not be discussed here. The C-H bond activation is a common phenomenon in the ESI conditions [21][22][23], but it cannot be used in the study of the anion-interactions. The presence/lack of NO 2 group on the aromatic ring surely affects the C-H bond activation, thus it cannot be concluded that the observed differences are caused by the anion-interactions.…”

Structural Determinants of Cisplatin and Transplatin Binding to the Met-Rich Motif of Ctr1: A Computational Spectroscopy Approach

“…Herein, we have addressed this issue by using computational tools. Simulation approaches are indeed widely used to investigate cisplatin and its interactions with biomolecules. − Specifically, we have used hybrid Car–Parrinello density functional theory-based QM/MM simulations − on models of platinated Mets7, extracted from available experimental information . We have already used this approach for platinated DNA. − These models contain the platinum moieties ([PtCl] + , [Pt(H 2 O)] 2+ , [Pt(OH)] + , and trans- [Pt(NH 3 ) 2 ] 2+ ).…”

Formation of Organometallic Species, [M – H]+ Ions and Radical Cations upon Mass Spectrometric Fragmentation of Mercury–Crown Ether Complexes

“…Activation of the c-H bond is known to occur upon mass spectrometric decomposition of metal complexes. [12][13][14][15] the third pathway involves the loss of the neutral Hgclo 4 molecule yielding the radical cation [B12C4] +• (analogous processes have already been observed under ESI conditions [16][17][18] ). this process is a result of interaction between the aromatic ring and the mercury cation, with the latter being reduced (Hg 2+ + e = Hg + , the electron is abstracted from the aromatic ring to the mercury cation).…”