The First Ruthenium-Based Paullones: Syntheses, X-ray Diffraction Structures, and Spectroscopic and Antiproliferative Properties in Vitro

Two novel paullone derivatives, namely, 6-(α-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L1) and 9-bromo-6-(α-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L2), have been prepared. The reaction of cis-[RuCl2(DMSO)4] (DMSO = dimethyl sulfoxide) with L1 and L2 in a 1:1 molar ratio in dry ethanol at 50 °C afforded the
complexes trans-[RuIICl2(DMSO)2L1] (1a) and trans-[RuIICl2(DMSO)2L2] (1b) in 26 and 30% yield, respectively. The
reaction carried out from the same starting compounds in a 1:2 molar ratio at 75 °C led to the formation of
[RuIICl(DMSO)(L1)2]Cl (2a) and [RuIICl(DMSO)(L2)2]Cl (2b) in 16 and 23% yield, correspondingly. The products
were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, electrospray ionization
mass spectrometry, IR spectroscopy, electronic spectra, cyclic voltammetry, and X-ray crystallography (L1, L2, 1a,
and 2b). Complexes 2a and 2b exhibit remarkable antiproliferative activity in three human carcinoma cell lines,
A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma). The novel complexes
show an intercalative mode of interaction with DNA, which may render them attractive alternatives to metal compounds
with a coordinative mode of interaction.

两种新颖的保卢尼衍生物，即6-(α-吡啶甲氨基)-7,12-二氢吲哚[3,2-d][1]苯并噁唑啉(L1)和9-溴-6-(α-吡啶甲氨基)-7,12-二氢吲哚[3,2-d][1]苯并噁唑啉(L2)已被合成。在无水乙醇中，以1:1的摩尔比，于50°C下将cis-[RuCl2(DMSO)4]（DMSO = 二甲基亚砜）与L1和L2反应，分别得到了trans-[RuIICl2(DMSO)2L1]（1a）和trans-[RuIICl2(DMSO)2L2]（1b）的复合物，产率分别为26%和30%。以相同的起始化合物，以1:2的摩尔比，在75°C下进行反应，相应地形成了[RuIICl(DMSO)(L1)2]Cl（2a）和[RuIICl(DMSO)(L2)2]Cl（2b），产率分别为16%和23%。通过元素分析、一维和二维核磁共振波谱、电喷雾电离质谱、红外光谱、电子光谱、循环伏安法和X射线晶体学（L1、L2、1a和2b）对产物进行了表征。复合物2a和2b在三种人类癌细胞系（A549非小细胞肺癌、CH1卵巢癌和SW480结肠癌）中表现出显著的抗增殖活性。这些新颖的复合物与DNA的相互作用模式为嵌合式，这可能使它们成为具有配位式相互作用的金属化合物的吸引人替代品。