通过电喷雾离子化质谱（ESI-MS），研究了光激活的六端人端粒DNA单元序列（5'-T1T2A3G4G5G6-3'，I）与光活化重氮基二羟基氯金(IV)前药，trans，trans，trans-[Pt(N3)2(OH)2(py)2]（py = pyridine；1）的相互作用。在初级质谱中，检测到两个主要的单铂化I附加物，它们分别是带有结合Pt基团的trans-[PtII(N3)(py)2]+（1'）和trans-[PtII(py)2]2+（1''）。由于通常在DNA中1'是复合物1光解时产生的主要还原Pt(II)物种，而之前很少检测到1''作为主要还原PtII物种，因此观察到这两种PtII物种形成的高丰度且几乎相等强度的铂化DNA附加物是罕见的。随后，通过碰撞诱导解离（CID）的串联质谱分析显示，在前一附加物{I + 1'}2+中，G6和A3是铂化位点。而在后者的附加物{I + 1''}2+中，鉴定出G4和G6位点之后，可以推测存在潜在的链内交联。此外，质谱还检测到由1'与G4和G6处发生铂化的双铂化I附加物以及含有碱基氧化的单铂化I附加物等其他次要铂化附加物。由于富含鸟嘌呤并且对氧化敏感，因此1引起的氧化很可能发生在鸟嘌呤上。根据先前的报道，氧化附加物被推测为8-羟基鸟嘌呤，螺虫亚氨基二恶嗪（Sp），2,6-二氨基-4-羟基-5-甲酰胞嘧啶（FapyG），5-胍基二恶嗪（Gh）和/或去氢胍基二恶嗪（DGh）。所得到的结果为光活化Pt(IV)抗癌前药与人类端粒DNA之间的光反应提供了有用的化学信息。Pt(IV)前药对人类端粒DNA的特殊损伤暗示了其在Pt(IV)前药机制中的活跃作用，并进一步支持复合物1与DNA反应的独特序列依赖性光相互作用特征。

The interaction of a photoactivatable diazidodihydroxido Pt(IV) prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2] (py = pyridine; 1), with a hexamer straight human telomeric DNA unit sequence (5'-T1T2A3G4G5G6-3', I) upon light irradiation was investigated by electrospray ionization mass spectroscopy (ESI-MS). In the primary mass spectrum, two major mono-platinated I adducts with the bound Pt moieties, trans-[PtII(N3)(py)2]+ (1') and trans-[PtII(py)2]2+ (1''), respectively, were detected. It is rare to observe such high abundance and nearly equal intensity platinated DNA adducts formed by these two PtII species because 1' is usually the only major reduced Pt(II) species produced by the photodecomposition of complex 1 in the presence of DNA while 1'' was rarely detected as the major reduced PtII species reported previously. Subsequent tandem mass spectrometric analysis by collision-induced dissociation (CID) showed that in the former adduct {I + 1'}2+, G6 and A3 were the platination sites. While in the latter adduct {I + 1''}2+, a potential intrastrand crosslink was speculated after G4 and G6 sites were identified. Additionally, other minor platinated adducts like di-platinated I adduct by 1' with platination sites at G4 and G6 and mono-platinated I adducts containing base oxidation were also detected by mass spectrometry. Due to the rich guanines and their sensitivity to oxidation, the oxidation induced by 1 most probably occurred at guanine. The oxidation adducts were proposed as 8-hydroxyl guanine, spiroiminodihydantoin (Sp), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), 5-guanidinohydantoin (Gh), and/or dehydroguanidinohydantoin (DGh) referring to previous reports. The obtained results provide useful chemical information about the photoreaction between photoactivatable Pt(IV) anticancer prodrugs and human telomeric DNA. Such special damages of Pt(IV) prodrugs on human telomeric DNA implicate its active role in the mechanism of Pt(IV) prodrugs and further support the unique sequence-dependent photointeraction profile of complex 1 reacting with DNA.