We present a rapid and efficient method to generate a family of platinum supramolecular square complexes, including previously inaccessible targets, through the use of ball milling mechanochemistry. This one-pot, two-step process occurs in minutes and enables the synthesis of the squares [Pt₄(en)₄(N∩N)₄][CF₃SO₃]₈ (en= ethylenediamine, N∩N = 4,4′-bipyridine derivatives) from commercially available precursor K₂PtCl₄ in good to excellent yields. In contrast, solution-based assembly requires heating the reagents for weeks and gives lower yields. Mechanistic investigations into this remarkable rate acceleration revealed that solution-based assembly (refluxing for days) results in the formation of large oligomeric side-products that are difficult to break down into the desired squares. On the other hand, ball milling in the solid state is rapid and appears to involve smaller intermediates. We examined the binding of the new supramolecular squares to guanine quadruplexes, including oncogene and telomere-associated DNA and RNA sequences. Sub-micromolar binding affinities were obtained by fluorescence displacement assays (FID) and isothermal titration calorimetry (ITC), with binding preference to telomere RNA (TERRA) sequences. ITC showed a 1:1 binding stoichiometry of the metallosquare to TERRA, while the stoichiometry was more complex for telomeric quadruplex DNA and a double-stranded DNA control.

中文翻译：

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用于鸟嘌呤四链体靶向的铂（II）方的高效快速机械化学组装

我们提出了一种快速有效的方法，通过使用球磨机械化学生成铂超分子方形配合物家族，包括以前难以接近的靶标。这一一锅，两步过程仅需数分钟即可完成，并能够合成正方形[Pt ₄（en）₄（N∩N）₄ ] [CF ₃ SO ₃ ] ₈（en =乙二胺，N = N = 4 （4'-联吡啶衍生物）购自市售前体K ₂ PtCl ₄产量高到极好。相反，基于溶液的组装需要将试剂加热数周，并且产率较低。对这种显着速率加速的机械研究表明，基于溶液的组装（回流数天）导致形成大的低聚物副产物，这些副产物难以分解为所需的正方形。另一方面，固态的球磨是快速的，并且似乎涉及较小的中间体。我们检查了新的超分子正方形与鸟嘌呤四联体，包括致癌基因和端粒相关的DNA和RNA序列的结合。亚微摩尔结合亲和力是通过荧光位移测定（FID）和等温滴定量热法（ITC）获得的，对端粒RNA（TERRA）序列的结合优先。ITC显示为1：