An experimental and theoretical investigation into the hydrolysis of dichloro(ethylenediamine)platinum(II) via electrospray mass spectrometry and density functional theory

Abstract

Dichloro(ethylenediamine)platinum(II), Pt(en)Cl 2 , was dissolved in H 2 O and D 2 O, and the resulting aqueous solutions were electrosprayed into a quadrupole ion-trap mass spectrometer. A series of major and minor ionic hydrolysis products were detected. These ions were then subjected to collision-induced dissociation. As an aid in interpreting the experimental results, density functional theory calculations were carried out. These computations permitted the structures and energetics associated with the hydrolysis products to be determined. An understanding of the hydrolysis of PtenCl 2 and related coordination complexes is essential in the rational design of metal-based drugs. (J Am Soc Mass Spectrom 2009, 20, 1015-1029

Electrospray ionization mass spectrometry for the hydrolysis complexes of cisplatin: implications for the hydrolysis process of platinum complexes

“…In the present study, the cone voltage could not exceed 25 V to avoid in‐source fragmentation of DHC and to obtain the authentic isotopic pattern. This is likely the reason why the dihydrated complex was not observed in a previous series of hydrolysis investigations of Pd(en)Br 2 , Pd(en)Cl 2 and Pt(en)Cl 2 (en: ethylenediamine) in which a high cone voltage was used.…”

“…Platinum complexes are a major class of chemotherapeutic agents against cancer, with cisplatin [ cis ‐diamminedichloroplatinum (II)], carboplatin [ cis ‐diammine 1,1‐cyclobutane dicarboxylato platinum (II)], oxaliplatin (1 R , 2 R ‐diaminocyclohexane) oxalatoplatinum (II)) and nedaplatin [ cis ‐diammine‐glycolatoplatinum (II)] being first‐line representatives used for the treatment of a wide variety of cancers such as ovarian and testicular carcinomas Even though the platinum complexes have been widely used for cancer therapies since the first member cisplatin was discovered in the 1960s, the mechanisms of action and toxicity for these coordination complexes are still not completely understood . It is generally accepted that the mode of action of platinum complexes consists of binding of the hydrolyzed complexes to the DNA.…”

“…This requires activation through non‐enzyme‐dependent hydrolysis. Through this binding to the DNA and reaction with other biologically important molecules, they exert an anticancer activity but also cause undesirable side effects such as cytotoxicity and nephrotoxicity . Therefore, understanding the hydrolysis process of platinum complexes is of considerable significance to elucidate the mechanisms behind the anticancer and toxic effects and also to pave the way for the development of new coordination complexes in the fight against cancer.…”

Synthesis, characterization and cytotoxicity studies of palladium(II)–proflavine complexes

“…3), in contrast to the spectra of some other Pd(II) compounds in aqueous solution which exhibited multinuclear Pd(II) species believed to have been formed during the ESI vaporization process [30,31]. The Pd(proflavine)-containing species identified and matched by simulation were [Pd(terpy)(proflavine)](NO 3 ) + , m/z 609.60, and [Pd(proflavine)(NO 3 )] + , m/z 376.20.…”

Investigation on the hydrolysis of the anticancer drug cisplatin by Fourier transform ion cyclotron resonance mass spectrometry

“…A similar phenomenon has been reported during the CID process of dichloro(ethylenediamine)platinum(II). [14] In order to avoid the reaction in the gas phase, the sample cone voltage was set at 20 V in the following experiments. The ion clusters of Pt(NH 3 ) 3 Cl and Pt(NH 3 ) 2 (CH 3 OH)Cl were also observed with very low abundance.…”