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

Abstract

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 (M1–M3) and two ionic (M4 and M5) 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 (M1–M5) 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 (M1–M5) 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 (M1–M5). Although the organometallic molecule 3 is almost seven times more potent than cisplatin, the antiproliferative potencies of the macrocycles (M1–M5) are up to 17 times better than cisplatin. Annexin V‐FITC assay studies show that post‐treatment with the organometallic 3, or the macrocycles (M1–M5), the A549 cancer cells are present in the early apoptosis stage.