Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO − binding mode
Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO − binding mode
复制标题
通过 IMPD 作用光谱法测定精氨酸连接的顺铂复合物的结构：精氨酸通过 NO – 结合模式与铂结合
DOI：
10.1039/d1cp03407c
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发表时间：
2021
影响因子：
3.3
通讯作者：
Chow, C. S.
中科院分区：
文献类型：
--
作者：
He, C. C.;Hamlow, L. A.;Kimutai, B.;Roy, H. A.;Devereaux, Zachary J.;Cunningham, N. A.;Martens, J.;Berden, G.;Oomens, J.;Chow, C. S.
顺铂，（NH3）2PtCl2，作为一种成功的金属抗癌药物已经有半个多世纪的历史了。它的类似物Argplatin，精氨酸连接的顺铂（Arg）PtCl2，正在研究中，因为它对DNA和RNA的反应性不同于顺铂。为了了解其改变反应性的基础，用红外多光子解离（IRMPD）作用光谱在红外指纹区和氢拉伸区检测了去质子化和钠阳离子化形式的Argplatin [(Arg- h)PtCl2]−和[(Arg)PtCl2 + Na]+。利用密度泛函理论方法进行互补电子结构计算，以表征这些配合物的稳定结构并预测其红外光谱。将这些铂配合物的各种稳定构象的理论红外光谱预测与其测量的IRMPD光谱进行比较，可以确定Arg与Pt金属中心的结合模式。在[(Arg- h)PtCl2]−和[(Arg)PtCl2 + Na]+配合物中，精氨酸以双齿方式与Pt结合到主氨基氮和羧酸氧原子上，即NO -结合模式。Arg的中性侧链也与Pt中心相互作用，在[(Arg- h)PtCl2]−络合物中实现额外的稳定。相反，在[(Arg)PtCl2 + Na]+配合物中，Na+与两个氯基配体结合，并且Arg的质子侧链通过与羧酸部分的氢键相互作用而稳定。这些发现与凝聚相结果一致，表明在电喷雾电离过程中，即使在不同的pH和离子强度下，精氨酸与Pt的NO -结合模式仍保持不变。
Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]− and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]− and [(Arg)PtCl2 + Na]+ complexes, the NO− binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]− complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO− binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.