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Two new di(2,2'-bipyridine) ligands, 2,6-bis([2,2'-bipyridin]-5-ylethynyl)pyridine ( L1 ) and bis(4-([2,2'-bipyridin]-5-ylethynyl)phenyl)methane ( L2 ) were synthesized and used to generate two metallosupramolecular [Fe 2 ( L ) 3 ](BF 4 ) 4 cylinders. The ligands and cylinders were characterized using elemental analysis, electrospray ionization mass spectrometry, UV-vis, 1 H-, 13 C and DOSY nuclear magnetic resonance (NMR) spectroscopies. The molecular structures of the [Fe 2 ( L ) 3 ](BF 4 ) 4 cylinders were confirmed using X-ray crystallography. Both the [Fe 2 ( L1 ) 3 ](BF 4 ) 4 and [Fe 2 ( L2 ) 3 ](BF 4 ) 4 complexes crystallized as racemic ( rac ) mixtures of the ΔΔ (P) and ΛΛ (M) helicates. However, 1 H NMR spectra showed that in solution the larger [Fe 2 ( L2 ) 3 ](BF 4 ) 4 was a mixture of the rac -ΔΔ/ΛΛ and meso -ΔΛ isomers. The host-guest chemistry of the helicates, which both feature a central cavity, was examined with several small drug molecules. However, none of the potential guests were found to bind within the helicates. In vitro cytotoxicity assays demonstrated that both helicates were active against four cancer cell lines. The smaller [Fe 2 ( L1 ) 3 ](BF 4 ) 4 system displayed low μM activity against the HCT116 (IC 50 = 7.1 ± 0.5 μM) and NCI-H460 (IC 50 = 4.9 ± 0.4 μM) cancer cells. While the antiproliferative effects against all the cell lines examined were less than the well-known anticancer drug cisplatin, their modes of action would be expected to be very different., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lisboa, Riisom, Vasdev, Jamieson, Wright, Hartinger and Crowley.)

New bis- quinoline ( L q ) and bis- isoquinoline-based ( L iq ) ligands have been synthesized, along with their respective homoleptic [Pd 2 ( L q or L iq ) 4 ] 4+ cages ( C q and C iq ). The ligands and cages were characterized by 1 H, 13 C and diffusion ordered (DOSY) NMR spectroscopies, high resolution electrospray ionization mass spectrometry (HR-ESIMS) and in the case of the bis -quinoline cage, X-ray crystallography. The crystal structure of the C q architecture showed that the [Pd 2 ( L q ) 4 ] 4+ cage formed a twisted meso isomer where the [Pd( quinoline ) 4 ] 2+ units at either end of the cage architecture adopt the opposite twists (left and right handed). Conversely, Density Functional Theory (DFT) calculations on the C iq cage architecture indicated that a lantern shaped conformation, similar to what has been observed before for related [Pd 2 ( L tripy ) 4 ] 4+ systems (where L tripy = 2,6- bis (pyridin-3-ylethynyl)pyridine), was generated. The different cage conformations manifest different properties for the isomeric cages. The C iq cage is able to bind, weakly in acetonitrile, the anticancer drug cisplatin whereas the C q architecture shows no interaction with the guest under the same conditions. The kinetic robustness of the two cages in the presence of Cl - nucleophiles was also different. The C iq cage was completely decomposed into free L iq and [Pd(Cl) 4 ] 2- within 1 h. However, the C q cage was more long lived and was only fully decomposed after 7 h. The new ligands ( L iq and L q ) and the Pd(II) cage architectures ( C iq and C q ) were assessed for their cytotoxic properties against two cancerous cell lines (A549 lung cancer and MDA-MB-231 breast cancer) and one non-cancerous cell line (HDFa skin cells). It was found that L q and C q were both reasonably cytotoxic (IC 50S ≈ 0.5 μM) against A549, while C iq was slightly less active (IC 50 = 7.4 μM). L iq was not soluble enough to allow the IC 50 to be determined against either of the two cancerous cell lines. However, none of the molecules showed any selectivity for the cancer cells, as they were all found to have similar cytotoxicities against HDFa skin cells (IC 50 values ranged from 2.6 to 3.0 μM).