Crystal structure and cytotoxic activities of a bis(pyrrolyl-imine) gold(III) complex

A gold(III) complex with N,N′-ethylenebis(pyrrol-2-yl-methyleneamine) (H2pyren) was synthesized and characterized by physicochemical and spectroscopic measurements. Density functional theory (DFT) studies and cytotoxic assays were performed. Infrared, mass spectrometry, and 1H, 13C, and {15N,1H} nuclear magnetic resonance analyses indicate that pyren is deprotonated and gold(III) is four coordinate in a square planar environment, with the pyrrole and imine nitrogens as donors. The structure was confirmed by powder X-ray diffraction and confirmed as a minimum of the potential energy surface by DFT. Cytotoxic activity of [Au(pyren)]+ was active against three tumorigenic cell lines with IC50 values of 35 μM. Interaction studies with CT-DNA by fluorescence and competition with ethidium bromide (EB) showed a quenching of the emission band of DNA with a Stern–Volmer quenching constant value of (3.0 ± 0.1) × 104 M−1 and a decrease in fluorescence quenching of EB-DNA system, respectively, confirming that DNA is a possible target for the complex via an intercalative binding, which was confirmed by DNA conformational changes observed with circular dichroism spectroscopy.

合成了一种以N,N′-亚乙基双(吡咯-2-亚甲基胺)（H2pyren）为配体的金(III)配合物，并通过物理化学与光谱学测试手段完成表征。开展了密度泛函理论（Density Functional Theory, DFT）研究与细胞毒性实验。红外光谱、质谱以及1H、13C与{15N,1H}核磁共振分析结果显示，配体pyren发生去质子化，金(III)中心为四配位结构，处于平面正方形配位环境中，配位原子为吡咯氮与亚胺氮。该配合物的结构通过粉末X射线衍射得以验证，且经DFT计算证实其为势能面上的极小值点。[Au(pyren)]+对三种致瘤细胞系展现出细胞毒性活性，半数抑制浓度（IC50）为35 μM。通过荧光光谱法与溴化乙锭（Ethidium Bromide, EB）竞争实验研究该配合物与小牛胸腺DNA（Calf Thymus DNA, CT-DNA）的相互作用：结果显示DNA的发射峰发生猝灭，斯特恩-沃尔默猝灭常数为(3.0 ± 0.1) × 10^4 M⁻¹；同时EB-DNA体系的荧光猝灭效应减弱，证实该配合物可通过插入结合方式靶向DNA，这一结论进一步被圆二色光谱观测到的DNA构象变化所验证。