Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma "La Sapienza", P.le A. Moro 5, 00185, Rome, Italy.
Department of Chemistry and Chemical Technologies, Università della Calabria, Ponte P. Bucci Cubo 14c, 87036, Arcavacata di Rende, Italy.
J Am Soc Mass Spectrom. 2019 Oct;30(10):1881-1894. doi: 10.1007/s13361-019-02186-7. Epub 2019 Apr 12.
Kinetically inert platinum(IV) complexes are receiving growing attention as promising candidates in the effort to develop safe and valid alternatives to classical square-planar Pt(II) complexes currently used in antineoplastic therapy. Their antiproliferative activity requires intracellular Pt(IV)-Pt(II) reduction (activation by reduction). In the present work, a set of five Pt(IV) complexes has been assayed using mass spectrometry-based techniques, i.e., collision-induced dissociation (CID), and IR multiple photon dissociation (IRMPD) spectroscopy, together with ab initio theoretical investigations. Breakdown and reduction mechanisms are observed that lead to Pt(II) species. Evidence is found for typically transient Pt(III) intermediates along the dissociation paths of isolated, negatively charged (electron-rich) Pt(IV) prodrug complexes.
动力学惰性的铂(IV)配合物作为有前途的候选物，正在受到越来越多的关注，以开发安全有效的替代物，替代目前用于抗肿瘤治疗的经典平面正方形 Pt(II)配合物。它们的增殖抑制活性需要细胞内 Pt(IV)-Pt(II)还原（还原激活）。在本工作中，使用基于质谱的技术（即碰撞诱导解离（CID）和红外多光子解离（IRMPD）光谱）以及从头理论研究，对一组五个 Pt(IV)配合物进行了测定。观察到导致 Pt(II)物种的断裂和还原机制。在分离的、带负电荷（富电子）Pt(IV)前药配合物的解离路径中，发现了通常是瞬态 Pt(III)中间体的证据。
