Ricerc@Sapienza

Cisplatin and transplatin (cis- and trans-[PtCl2(NH3)2]) have been allowed to react with methionine (Met)
in water solution in a study aimed to characterize the monofunctional complex primarily formed. The
thioether function of methionine is known to have a very high affinity for square planar platinum(II) and
sulfur-containing biomolecules have been proposed as a cisplatin drug reservoir on the way to
platination at DNA. Both cisplatin and transplatin yield [PtCl(NH3)2Met]+ complexes, delivered by
electrospray ionization in the gas phase and sampled as isolated species using tools based on mass
spectrometry. The collision induced dissociation spectra of both cis-[PtCl(NH3)2Met]+ and trans-
[PtCl(NH3)2Met]+ are quite similar and also the transport properties assayed by ion mobility mass
spectrometry do not allow any appreciable discrimination. However, the vibrational spectra obtained by
IR multiple photon absorption (IRMPD) spectroscopy show distinct features. Their analysis, supported by
quantum chemical calculations, has revealed that while cisplatin attack is mainly directed to the sulfur
atom of Met, transplatin shows a more balanced partition between sulfur and nitrogen binding. Among
the vibrational signatures characterizing cis-[PtCl(NH3)2Met]+ and trans-[PtCl(NH3)2Met]+ complexes, the
asymmetric NH2 stretching of the a-amino group of the amino acid at ca. 3440 cm-1 is peculiar and
diagnostic of S-platination. IRMPD kinetics evaluated at this frequency support the prevailing S-attack by
cisplatin while approximately a 1 : 2 ratio of S- versus N-coordination is observed by transplatin, to be
possibly related to the trans effect at the platinum center.