Self-assembled neutral and ionic [2 + 2] metallomacrocycles using a new flexible ditopic Pt(II)-based organometallic tecton bearing a pyrimidine motif: Facile syntheses and enhanced anticancer potency

A new di-platinum(II) organometallic compound ( 3 ) has been synthesized from a readily available pyrimidine derivative in two steps. 3 is a conformationally flexible molecule due to the presence of ethereal linkages. The application of 3 as an acceptor tecton in supramolecular chemistry was explored using coordination-driven self-assembly protocol. Thus, three neutral ( M ₁ – M ₃ ) and two ionic ( M ₄ and M ₅ ) metallomacrocycles were obtained in high yields, the structures of which included biologically active pyrimidine and π-conjugated trans-Pt(II)-alkynyl motifs. Formation of these five flexible [2 + 2] ensembles ( M ₁ – M ₅ ) was confirmed using FT-IR and NMR spectroscopy (¹H, ³¹P{¹H}, ¹³C{¹H}, and ¹H DOSY) as well as HRMS experiments. DFT calculations suggest that the macrocycles have nano-scalar dimensions with well-defined cavities. Cytotoxicity of 3 and macrocycles ( M ₁ – M ₅ ) were estimated against A549 human lung cancer cell line. Results indicate improvement in cytotoxicity upon self-assembly of 3 with neutral and ionic donor tectons to yield, respectively ionic and neutral macrocycles ( M ₁ – M ₅ ). Although the organometallic molecule 3 is almost seven times more potent than cisplatin, the antiproliferative potencies of the macrocycles ( M ₁ – M ₅ ) are up to 17 times better than cisplatin. Annexin V-FITC assay studies show that post-treatment with the organometallic 3 , or the macrocycles ( M ₁ – M ₅ ), the A549 cancer cells are present in the early apoptosis stage.