AUTHOR=Lisboa Lynn S. , Riisom Mie , Vasdev Roan A. S. , Jamieson Stephen M. F. , Wright L. James , Hartinger Christian G. , Crowley James D. 

TITLE=Cavity-Containing [Fe2L3]4+ Helicates: An Examination of Host-Guest Chemistry and Cytotoxicity

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.697684

DOI=10.3389/fchem.2021.697684

ISSN=2296-2646

ABSTRACT=<p>Two new di(2,2′-bipyridine) ligands, 2,6-bis([2,2′-bipyridin]-5-ylethynyl)pyridine (<bold>L1</bold>) and bis(4-([2,2′-bipyridin]-5-ylethynyl)phenyl)methane (<bold>L2</bold>) were synthesized and used to generate two metallosupramolecular [Fe<sub>2</sub>(<bold>L</bold>)<sub>3</sub>](BF<sub>4</sub>)<sub>4</sub> cylinders. The ligands and cylinders were characterized using elemental analysis, electrospray ionization mass spectrometry, UV-vis, <sup>1</sup>H-, <sup>13</sup>C and DOSY nuclear magnetic resonance (NMR) spectroscopies. The molecular structures of the [Fe<sub>2</sub>(<bold>L</bold>)<sub>3</sub>](BF<sub>4</sub>)<sub>4</sub> cylinders were confirmed using X-ray crystallography. Both the [Fe<sub>2</sub>(<bold>L1</bold>)<sub>3</sub>](BF<sub>4</sub>)<sub>4</sub> and [Fe<sub>2</sub>(<bold>L2</bold>)<sub>3</sub>](BF<sub>4</sub>)<sub>4</sub> complexes crystallized as racemic (<italic>rac</italic>) mixtures of the ΔΔ (P) and ΛΛ (M) helicates. However, <sup>1</sup>H NMR spectra showed that in solution the larger [Fe<sub>2</sub>(<bold>L2</bold>)<sub>3</sub>](BF<sub>4</sub>)<sub>4</sub> was a mixture of the <italic>rac</italic>-ΔΔ/ΛΛ and <italic>meso</italic>-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. <italic>In vitro</italic> cytotoxicity assays demonstrated that both helicates were active against four cancer cell lines. The smaller [Fe<sub>2</sub>(<bold>L1</bold>)<sub>3</sub>](BF<sub>4</sub>)<sub>4</sub> system displayed low μM activity against the HCT116 (IC<sub>50</sub> = 7.1 ± 0.5 μM) and NCI-H460 (IC<sub>50</sub> = 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.</p>