[Pd₂(hextrz)₄]⁴⁺ is a quadruply stranded helicate, a novel bioinorganic complex designed to mimic the structure and function of proteins due to its high stability and supramolecular size. We have previously reported that [Pd₂(hextrz)₄]⁴⁺ exhibited cytotoxicity toward a range of cell lines, with IC₅₀ values ranging from 3 to 10 μM. Here we demonstrate that [Pd₂(hextrz)₄]⁴⁺ kills cells by forming pores within the cell membrane, a mechanism of cell death analogous to the naturally occurring cytolytic peptides. [Pd₂(hextrz)₄]⁴⁺ induced cell death is characterized by an initial influx of Ca²⁺, followed by nuclear condensation and mitochondrial swelling. This is accompanied by progressive cell membrane damage that results in the formation of large blebs at the cell surface. This allows the efflux of molecules from the cell leading to loss of cell viability. These data suggest that it may be possible to design metallo-supramolecular complexes to mimic the cytotoxic action of pore forming proteins and peptides and so provide a new class of drug to treat cancer, autoimmune disorders, and microbial infection.

中文翻译：

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四链金属-超分子螺旋[Pd2（hextrz）4] 4+充当细胞溶解肽的分子模拟。

[Pd ₂（hextrz）₄ ] ⁴⁺是四链螺旋，是一种新型的生物无机复合物，由于其高稳定性和超分子大小，可模拟蛋白质的结构和功能。我们先前曾报道[Pd ₂（hextrz）₄ ] ⁴⁺对一系列细胞系表现出细胞毒性，IC ₅₀值为3至10μM。在这里，我们证明了[Pd ₂（hextrz）₄ ] ⁴⁺通过在细胞膜上形成孔杀死细胞，这是一种类似于天然溶细胞肽的细胞死亡机制。[Pd ₂（hextrz）₄ ]⁴⁺诱导的细胞死亡的特征是最初流入Ca ²⁺，然后是核浓缩和线粒体肿胀。这伴随着进行性细胞膜损伤，导致在细胞表面形成大气泡。这使得分子从细胞流出，导致细胞活力丧失。这些数据表明，可能有可能设计金属-超分子复合物来模拟孔形成蛋白和肽的细胞毒性作用，从而为治疗癌症，自身免疫性疾病和微生物感染提供了新的一类药物。