Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502285, Telangana, India.
Department of Biotechnology, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502285, Telangana, India.
Dalton Trans. 2020 Aug 11;49(31):10772-10785. doi: 10.1039/d0dt01788d.
Polypyridyl backbone nitrosyl complexes of ruthenium with the molecular framework [RuII(antpy)(bpy)NO+/˙]n+ 43 (n = 3), 42 (n = 2), where antpy = 4'-(anthracene-9-yl)-2,2':6',2''-terpyridine and bpy = 2,2'-bipyridine, were synthesized via a stepwise synthetic route from the chloro precursor RuII(antpy)(bpy)(Cl) 1 and RuII(antpy)(bpy)(CH3CN)2 22 and RuII(antpy)(bpy)(NO2) 3. After column chromatographic purification, all the synthesized complexes were fully characterized using different spectroscopic and analytical techniques including mass spectroscopy, 1H NMR, FT-IR and UV-vis spectrophotometry. The Ru-NO stretching frequency of 43 was observed at 1941 cm-1, which suggests moderately strong Ru-NO bonding. A massive shift in the νNO frequency occurred at Δν = 329 cm-1 (solid) upon reducing 43 to 42. To understand the molecular integrity of the complexes, the structure of 3 was successfully determined by X-ray crystallography. The redox properties of 43 were thoroughly investigated together with the other precursor complexes. The rate constants for the first-order photo-release of NO from 43 and 42 were determined to be 8.01 × 10-3 min-1 (t1/2 ∼ 86 min) and 3.27 × 10-2 min-1 (t1/2 ∼ 21 min), respectively, when exposed to a 200 W Xenon light. Additionally, the photo-cleavage of Ru-NO occurred within ∼2 h when 43 was irradiated with an IR light source (>700 nm) at room temperature. The first-order rate constant of 9.4 × 10-3 min-1 (t1/2 ∼ 73 min) shows the efficacy of the system and its capability to release NO in the photo-therapeutic window. The released NO triggered by light was trapped by reduced myoglobin, a biologically relevant target protein. The one-electron reduction of 43 to 42 was systematically carried out chemically (hydrazine hydrate), electrochemically and biologically. In the biological reduction, it was found that the reduction is much slower with double-stranded DNA compared to a single-stranded oligonucleotide (CAAGGCCAACCGCGAGAAGATGAC). Moreover, 43 exhibited significant photo-toxicity to the VCaP prostate cancer cell line upon irradiation with a visible light source (IC50 ∼ 8.97 μM).
钌的多吡啶基硝基亚胺配合物具有[RuII(antpy)(bpy)NO+/˙]n+43(n=3)、42(n=2)的分子框架，其中antpy=4'-(蒽-9-基)-2,2':6',2''-三联吡啶，bpy=2,2'-联吡啶。通过从氯前体RuII(antpy)(bpy)(Cl)1和RuII(antpy)(bpy)(CH3CN)222以及RuII(antpy)(bpy)(NO2)3的逐步合成路线合成了这些配合物。在经过柱色谱纯化后，使用不同的光谱和分析技术，包括质谱、1H NMR、FT-IR 和紫外可见分光光度法，对所有合成的配合物进行了充分的表征。43的 Ru-NO 伸缩频率在 1941 cm-1 处观察到，这表明 Ru-NO 键具有中等强度。当将43还原为42 时，νNO 频率发生了 329 cm-1(固体)的巨大位移。为了了解配合物的分子完整性，成功地通过 X 射线晶体学确定了3的结构。彻底研究了43 与其他前体配合物的氧化还原性质。当暴露于 200 W 氙灯下时，43 和42 中 NO 的一阶光释放的速率常数分别确定为 8.01×10-3 min-1(t1/2∼86 min)和 3.27×10-2 min-1(t1/2∼21 min)。此外，当43 在室温下用大于 700nm 的红外光源照射时，Ru-NO 的光裂解在约 2 小时内发生。9.4×10-3 min-1(t1/2∼73 min)的一级速率常数表明了该系统的功效及其在光治疗窗口中释放 NO 的能力。光触发的释放的 NO 被生物相关靶蛋白还原型肌红蛋白捕获。通过化学方法(水合肼)、电化学方法和生物学方法系统地进行了43 到42 的单电子还原。在生物学还原中，与单链寡核苷酸(CAAGGCCAACCGCGAGAAGATGAC)相比，发现与双链 DNA 的还原慢得多。此外，当用可见光照射时，43 对 VCaP 前列腺癌细胞系表现出显著的光毒性(IC50∼8.97 μM)。
