Paciotti Roberto, Corinti Davide, De Petris Alberto, Ciavardini Alessandra, Piccirillo Susanna, Coletti Cecilia, Re Nazzareno, Maitre Philippe, Bellina Bruno, Barran Perdita, Chiavarino Barbara, Elisa Crestoni Maria, Fornarini Simonetta
Dipartimento di Farmacia, Università G. D'Annunzio, Chieti I-66100, Italy.
Phys Chem Chem Phys. 2017 Oct 11;19(39):26697-26707. doi: 10.1039/c7cp05203k.
Cisplatin and transplatin (cis- and trans-[PtCl(NH)]) 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(NH)Met] 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(NH)Met] and trans-[PtCl(NH)Met] 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(NH)Met] and trans-[PtCl(NH)Met] complexes, the asymmetric NH stretching of the α-amino group of the amino acid at ca. 3440 cm 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.
在一项旨在表征主要形成的单功能配合物的研究中，顺铂和反铂（顺式和反式 - [PtCl(NH)]）已被允许在水溶液中与蛋氨酸（Met）反应。已知蛋氨酸的硫醚官能团对平面正方形铂（II）具有非常高的亲和力，并且含硫生物分子已被提议作为顺铂在DNA上进行铂化过程中的药物储存库。顺铂和反铂都产生[PtCl(NH)Met]配合物，通过气相电喷雾电离产生，并使用基于质谱的工具作为分离的物种进行采样。顺式 - [PtCl(NH)Met]和反式 - [PtCl(NH)Met]的碰撞诱导解离光谱非常相似，并且通过离子淌度质谱测定的传输性质也无法进行任何明显的区分。然而，通过红外多光子吸收（IRMPD）光谱获得的振动光谱显示出明显的特征。在量子化学计算的支持下对其进行分析后发现，虽然顺铂的攻击主要针对蛋氨酸的硫原子，但反铂在硫和氮结合之间表现出更平衡的分配。在表征顺式 - [PtCl(NH)Met]和反式 - [PtCl(NH)Met]配合物的振动特征中，氨基酸α - 氨基的不对称NH伸缩振动在约3440 cm处是独特的，并且是S - 铂化的诊断特征。在此频率下评估的IRMPD动力学支持顺铂主要进行S - 攻击，而反铂观察到S - 配位与N - 配位的比例约为1∶2，这可能与铂中心的反位效应有关。
