Department of Energy and Chemical Engineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea; Innovation Center for Chemical Engineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea.
CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India.
J Inorg Biochem. 2018 Dec;189:17-29. doi: 10.1016/j.jinorgbio.2018.08.009. Epub 2018 Aug 16.
The use of organic compounds with known medicinal properties in the synthesis of metal-based complexes is an important alternative to improve the biological activity of metal-based drugs. The reaction of [M(arene)Cl] (M = Ru, arene = p-cymene and M = Ir, arene = pentamethylcyclopentadienyl, cp*) with avobenzone (1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione, AVBH) and KOH in methanol leads to the formation of the neutral complexes [Ru(p-cymene)(AVB)Cl] 1 and [Ir(cp*)(AVB)Cl] 2 (cp* = pentamethylcyclopentadienyl). Subsequent reaction of 1 and 2 with pyridyl derivative-BODIPY ligands, BDP and BDPCC (BODIPY = boron dipyrromethene, BDP = 4-dipyridine boron dipyrromethene, BDPCC = 4-ethynylpyridine boron dipyrromethene) in methanol gives a series of four new dicationic supramolecules: [Ru(p-cymene)(AVB)BDP][2CFSO] 3, [Ir(cp*)(AVB)BDP][2CFSO] 4, [Ru(p-cymene)(AVB)BDPCC][2CFSO] 5 and [Ir(cp*)(AVB)BDPCC][2CFSO] 6. The synthesized complexes are fully characterized using multiple analytical techniques, including elemental analysis, H NMR, C NMR, F NMR (NMR = Nuclear Magnetic Resonance), Infrared Radiation (IR), Electrospray Ionization-Mass Spectrometry (ESI-MS), Ultraviolet-visible (UV-Vis) and fluorescence spectroscopy. The structures of these complexes are further rationalized using density functional theory (DFT) calculations. The antiproliferative activity of the neutral and dinuclear cationic complexes is evaluated in vitro in different human cancer cell lines. These complexes are found to be active against different cancer cell lines with half maximal inhibitory concentration (IC) values between 1 and 5 μM. Complexes 5 and 6 displayed the lowest IC values in all the cell lines studied. The activity of 5 and 6 is comparable to that of the well-known chemotherapy drug doxorubicin. Detailed biophysical studies indicate that complexes 5 and 6 exhibit very good Deoxyribonucleic acid (DNA) binding properties, causing the unwinding of the double helix, which is a probable reason for their high cytotoxicity.
将具有已知药用特性的有机化合物用于合成金属基配合物是提高金属基药物生物活性的一种重要方法。[M(芳烃)Cl]（M=Ru，芳烃=p-枯烯；M=Ir，芳烃=五甲基环戊二烯基，cp*）与阿伏苯宗（1-(4-叔丁基苯基)-3-(4-甲氧基苯基)丙烷-1,3-二酮，AVBH）和 KOH 在甲醇中的反应导致中性配合物[Ru(p-枯烯)(AVB)Cl]1 和 [Ir(cp*)(AVB)Cl]2（cp*=五甲基环戊二烯基）的形成。随后，将 1 和 2 与吡啶衍生物-BODIPY 配体 BDP 和 BDPCC（BODIPY=硼二吡咯甲烷，BDP=4-二吡啶基硼二吡咯甲烷，BDPCC=4-乙炔基吡啶基硼二吡咯甲烷）在甲醇中反应，得到一系列四个新的二价阳离子超分子化合物：[Ru(p-枯烯)(AVB)BDP][2CFSO]3、[Ir(cp*)(AVB)BDP][2CFSO]4、[Ru(p-枯烯)(AVB)BDPCC][2CFSO]5 和 [Ir(cp*)(AVB)BDPCC][2CFSO]6。使用多种分析技术，包括元素分析、1H NMR、13C NMR、19F NMR（NMR=核磁共振）、红外辐射（IR）、电喷雾电离-质谱（ESI-MS）、紫外可见（UV-Vis）和荧光光谱，对合成的配合物进行了全面的表征。使用密度泛函理论（DFT）计算进一步合理化这些配合物的结构。在不同的人癌细胞系中体外评估了中性和双核阳离子配合物的抗增殖活性。这些配合物对不同的癌细胞系表现出活性，半数最大抑制浓度（IC）值在 1 到 5 μM 之间。在所有研究的细胞系中，复合物 5 和 6 的 IC 值最低。复合物 5 和 6 的活性与著名的化疗药物阿霉素相当。详细的生物物理研究表明，复合物 5 和 6 具有非常好的脱氧核糖核酸（DNA）结合特性，导致双螺旋的解旋，这可能是它们高细胞毒性的原因。
