Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma "La Sapienza", P. le A. Moro 5, 00185, Roma, Italy.
LCM, CNRS, Ecole Polytechnique, Institut Polytechnique de Paris, 91128, Palaiseau, France.
Angew Chem Int Ed Engl. 2020 Sep 1;59(36):15595-15598. doi: 10.1002/anie.202007597. Epub 2020 Aug 11.
Platinum(IV) complexes are extensively studied for their activity against cancer cells as potential substitutes for the widely used platinum(II) drugs. Pt complexes are kinetically inert and need to be reduced to Pt species to play their pharmacological action, thus acting as prodrugs. The mechanism of the reduction step inside the cell is however still largely unknown. Gas-phase activation of deprotonated platinum(IV) prodrugs was found to generate products in which platinum has a formal +3 oxidation state. IR multiple photon dissociation spectroscopy is thus used to obtain structural information helping to define the nature of both the platinum atom and the ligands. In particular, comparison of calculations at DFT, MP2 and CCSD levels with experimental results demonstrates that the localization of the radical is about equally shared between the d orbital of platinum and the p of nitrogen on the amino group, the latter acting as a non-innocent ligand.
铂(IV)配合物因其对癌细胞的活性而被广泛研究，作为广泛使用的铂(II)药物的潜在替代品。Pt 配合物动力学惰性，需要还原为 Pt 物种才能发挥其药理作用，因此充当前药。然而，铂(IV)前药在细胞内还原步骤的机制在很大程度上仍然未知。发现气相中去质子化的铂(IV)前药的活化生成其中铂具有形式+3 氧化态的产物。因此，使用红外多光子解离光谱获得有助于定义铂原子和配体性质的结构信息。特别是，与实验结果的 DFT、MP2 和 CCSD 水平的计算比较表明，自由基的定位在铂的 d 轨道和氨基上的氮的 p 轨道之间几乎平均分配，后者充当非无辜配体。
