A pyrrolyl-iminophosphine (PNNH) which would act as a potential terdentate ligand has been prepared by Schiff base reaction. Complexes [M(PNN)X] (M = Ni; X = Cl (1), Pd; X = Cl (2), Br (3), I (4), M = Pt; X = Cl (5)) were prepared. The title complexes were characterized by various spectroscopic (IR, 1H, 13C, and 31P NMR) and elemental analyses. The molecular structures of 1, 2, and 5 have been established by single-crystal X-ray crystallography, demonstrating a distorted square planar geometry comprising two 5-membered metallacyclic rings. Complexes 1 and 2 were found to crystallize in the orthorhombic while complex 5 crystallizes in the monoclinic. Cytotoxicities of the complexes along with PNNH were evaluated against A549 (lung), SK-OV-3 (ovarian), SM-MEL-2 (skin), and HCT15 (colon) human cancer cell lines by sulforhodamine B assay. Notably, the palladium(II) complex (2) shows the highest activity. Apoptosis activity along with the caspase inhibitor Z-VAD (Z-Val-Ala-Asp-fluoromethyl ketone) assay of 2 and 5 against A549 and HCT15 cancer cell lines were investigated to learn a mechanistic pathway for the observed cytotoxicity, practically eliminating an apoptotic cell-death route. Complexes 2 and 5 were studied to DNA cleavage assay and molecular docking simulation. The DNA (pcDNA3.0) cleavage experiment evaluates complex 5 interacting with DNA, more effectively, in comparison to complex 2. Molecular docking simulation of 2 and 5 toward DNA and GRP78 (glucose-regulated protein 78) was performed to predict binding sites of ligand-receptors and a plausible mechanistic aspect of metallodrug-action.

中文翻译：

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具有吡咯基-亚氨基膦（PNN）钳形的新型镍（II），钯（II）和铂（II）配合物：合成，晶体结构和细胞毒性活性。

通过席夫碱反应已经制备了可以用作潜在的齿状配体的吡咯基-亚氨基膦（PNNH）。配合物[M（PNN）X]（M = Ni; X = Cl（1），Pd; X = Cl（2），Br（3），I（4），M = Pt; X = Cl（5））准备。通过各种光谱（IR，1H，13C和31P NMR）和元素分析对标题配合物进行表征。1、2和5的分子结构已通过单晶X射线晶体学确定，表明包含两个5元金属环的扭曲的方形平面几何形状。发现复合物1和2在正交晶中结晶，而复合物5在单斜晶中结晶。通过磺基罗丹明B测定法评估了该复合物与PNNH对A549（肺），SK-OV-3（卵巢），SM-MEL-2（皮肤）和HCT15（结肠）人癌细胞系的细胞毒性。值得注意的是 钯（II）配合物（2）表现出最高的活性。研究了2和5的半胱天冬酶抑制剂Z-VAD（Z-Val-Ala-Asp-氟甲基酮）对A549和HCT15癌细胞系的凋亡活性，以了解观察到的细胞毒性的机制途径，实际上消除了凋亡细胞死亡路线。研究了复合物2和5，以进行DNA裂解分析和分子对接模拟。与复合物2相比，DNA（pcDNA3.0）裂解实验可更有效地评估复合物5与DNA的相互作用。进行2和5对DNA和GRP78（葡萄糖调节蛋白78）的分子对接模拟，以预测复合物5的结合位点。配体受体和金属药物作用的合理机理方面。研究了2和5的半胱天冬酶抑制剂Z-VAD（Z-Val-Ala-Asp-氟甲基酮）对A549和HCT15癌细胞系的凋亡活性，以了解观察到的细胞毒性的机制途径，实际上消除了凋亡细胞死亡路线。研究了复合物2和5，以进行DNA裂解分析和分子对接模拟。与复合物2相比，DNA（pcDNA3.0）裂解实验可更有效地评估复合物5与DNA的相互作用。进行2和5对DNA和GRP78（葡萄糖调节蛋白78）的分子对接模拟，以预测复合物5的结合位点。配体受体和金属药物作用的合理机理方面。研究了2和5的半胱天冬酶抑制剂Z-VAD（Z-Val-Ala-Asp-氟甲基酮）对A549和HCT15癌细胞系的凋亡活性，以了解观察到的细胞毒性的机制途径，实际上消除了凋亡细胞死亡路线。研究了复合物2和5，以进行DNA裂解分析和分子对接模拟。与复合物2相比，DNA（pcDNA3.0）裂解实验可更有效地评估复合物5与DNA的相互作用。进行2和5对DNA和GRP78（葡萄糖调节蛋白78）的分子对接模拟，以预测复合物5的结合位点。配体受体和金属药物作用的合理机理方面。