The rational design and selective self-assembly of flexible and unsymmetric ligands into large coordination complexes is an eminent challenge in supramolecular coordination chemistry. Here, we present the coordination-driven self-assembly of natural ursodeoxycholic-bile-acid-derived unsymmetric tris-pyridyl ligand (L) resulting in the selective and switchable formation of chiral stellated Pd6L8 and Pd12L16 cages. The selectivity of the cage originates in the adaptivity and flexibility of the arms of the ligand bearing pyridyl moieties. The interspecific transformations can be controlled by changes in the reaction conditions. The orientational self-sorting of L into a single constitutional isomer of each cage, i.e., homochiral quadruple and octuple right-handed helical species, was confirmed by a combination of molecular modelling and circular dichroism. The cages, derived from natural amphiphilic transport molecules, mediate the higher cellular uptake and increase the anticancer activity of bioactive palladium cations as determined in studies using in vitro 3D spheroids of the human hepatic cells HepG2.

CEITEC Central European Institute of Technology Masaryk University Kamenice 5 Brno CZ 62500 Czechia

Department of Biochemistry Faculty of Science Masaryk University Kamenice 5 Brno CZ 62500 Czechia

Department of Chemistry Faculty of Science Masaryk University Kamenice 5 Brno CZ 62500 Czechia

Department of Chemistry University of Jyvaskyla P O Box 35 Jyväskylä FI 40014 Finland

Department of Natural Drugs Faculty of Pharmacy Masaryk University Palackého 1946 1 Brno CZ 61200 Czechia

Institute of Physics University of Tartu W Ostwald Street 1 Tartu 50411 Estonia

National Center for Biomolecular Research Faculty of Science Masaryk University Kamenice 5 Brno CZ 62500 Czechia

RECETOX Faculty of Science Masaryk University Kotlarska 2 Brno CZ 61137 Czechia

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Saalfrank R. W., Stark A., Peters K., von Schnering H. G., Angew. Chem. Int. Ed. Engl. 1988, 27, 851–853.

Chakrabarty R., Mukherjee P. S., Stang P. J., Chem. Rev. 2011, 111, 6810–6918. PubMed PMC

Saha S., Regeni I., Clever G. H., Coord. Chem. Rev. 2018, 374, 1–14.

Ronson T. K., Carruthers C., Fisher J., Brotin T., Harding L. P., Rizkallah P. J., Hardie M. J., Inorg. Chem. 2010, 49, 675–685. PubMed

Bandi S., Pal A. K., Hanan G. S., Chand D. K., Chem. – Eur. J. 2014, 20, 13122–13126. PubMed

Dasary H., Sarkar M., Chand D. K., Chem. Commun. 2022, 58, 8480–8483. PubMed

Preston D., Inglis A. R., Crowley J. D., Kruger P. E., Chem. Asian J. 2019, 14, 3404–3408. PubMed

Sun Q.‐F., Sato S., Fujita M., Nat. Chem. 2012, 4, 330–333. PubMed

Debata N. B., Tripathy D., Sahoo H. S., Coord. Chem. Rev. 2019, 387, 273–298.

Tripathy D., Debata N. B., Naik K. C., Sahoo H. S., Coord. Chem. Rev. 2022, 456, 214396.

Pullen S., Tessarolo J., Clever G. H., Chem. Sci. 2021, 12, 7269–7293. PubMed PMC

Wu K., Benchimol E., Baksi A., Clever G. H., Nat. Chem. 2024, 16, 584–591. PubMed

Meng W., Ronson T. K., Nitschke J. R., Proc. Natl. Acad. Sci 2013, 110, 10531–10535. PubMed PMC

Bonakdarzadeh P., Pan F., Kalenius E., Jurček O., Rissanen K., Angew. Chem. Int. Ed. 2015, 54, 14890–14893. PubMed

Howlader P., Zangrando E., Mukherjee P. S., J. Am. Chem. Soc. 2020, 142, 9070–9078. PubMed

Howlader P., Mondal S., Ahmed S., Mukherjee P. S., J. Am. Chem. Soc. 2020, 142, 20968–20972. PubMed

Chen L.‐J., Yang H.‐B., Shionoya M., Chem. Soc. Rev. 2017, 46, 2555–2576. PubMed

Kikuchi T., Sato S., Fujita D., Fujita M., Chem. Sci. 2014, 5, 3257.

Barber B. E., Jamieson E. M. G., White L. E. M., McTernan C. T., Chem 2024, 10, 2792–2806.

Sato S., Yoshimasa Y., Fujita D., Yagi‐Utsumi M., Yamaguchi T., Kato K., Fujita M., Angew. Chem. 2015, 127, 8555–8559. PubMed

Domoto Y., Yamamoto K., Horie S., Yu Z., Fujita M., Chem. Sci. 2022, 13, 4372–4376. PubMed PMC

Jurček O., Bonakdarzadeh P., Kalenius E., Linnanto J. M., Groessl M., Knochenmuss R., Ihalainen J. A., Rissanen K., Angew. Chem. Int. Ed. 2015, 54, 15462–15467. PubMed

Jurček O., Nonappa, E. K. , Jurček P., Linnanto J. M., Puttreddy R., Valkenier H., Houbenov N., Babiak M., Peterek M., Davis A. P., Marek R., Rissanen K., Cell Rep. Phys. Sci. 2021, 2, 100303.

Sen S. K., Natarajan R., Inorg. Chem. 2019, 58, 7180–7188. PubMed

Jurček O., Chattopadhyay S., Kalenius E., Linnanto J. M., Kiesilä A., Jurček P., Radiměřský P., Marek R., Angew. Chem. Int. Ed. 2024, 63, e202409134. PubMed

Sawada T., Fujita M., Chem 2020, 6, 1861–1876.

Fujita D., Ueda Y., Sato S., Mizuno N., Kumasaka T., Fujita M., Nature 2016, 540, 563–566. PubMed

Bunzen J., Iwasa J., Bonakdarzadeh P., Numata E., Rissanen K., Sato S., Fujita M., Angew. Chem. Int. Ed. 2012, 51, 3161–3163. PubMed

Yokoyama H., Ueda Y., Fujita D., Sato S., Fujita M., Chem. – Asian J. 2015, 10, 2292–2295. PubMed

Fujita D., Ueda Y., Sato S., Yokoyama H., Mizuno N., Kumasaka T., Fujita M., Chem 2016, 1, 91–101.

Casini A., Woods B., Wenzel M., Inorg. Chem. 2017, 56, 14715–14729. PubMed

Cook T. R., Vajpayee V., Lee M. H., Stang P. J., Chi K.‐W., Acc. Chem. Res. 2013, 46, 2464–2474. PubMed PMC

Sepehrpour H., Fu W., Sun Y., Stang P. J., J. Am. Chem. Soc. 2019, 141, 14005–14020. PubMed PMC

Durník R., Šindlerová L., Babica P., Jurček O., Molecules 2022, 27, 2961. PubMed PMC

Yan Y., Huang J., Tang B. Z., Chem. Commun. 2016, 52, 11870–11884. PubMed

Kai S., Sakuma Y., Mashiko T., Kojima T., Tachikawa M., Hiraoka S., Inorg. Chem. 2017, 56, 12652–12663. PubMed

Díaz‐Torres R., Alvarez S., Dalton Trans. 2011, 40, 10742. PubMed

Komine S., Takahashi S., Kojima T., Sato H., Hiraoka S., J. Am. Chem. Soc. 2019, 141, 3178–3186. PubMed

It was previously observed (please see reference 22) with a similar bile‐acid‐based ligand, that ligand's rotation in either dimeric Pd

Suzuki K., Kawano M., Fujita M., Angew. Chem. 2007, 119, 2877–2880.

Lee H., Han J., Kim D., Jung O.‐S., Dalton Trans. 2021, 50, 14849–14854. PubMed

Zhang T., Zhou L.‐P., Guo X.‐Q., Cai L.‐X., Sun Q.‐F., Nat. Commun. 2017, 8, 15898. PubMed PMC

Fujita D., Takahashi A., Sato S., Fujita M., J. Am. Chem. Soc. 2011, 133, 13317–13319. PubMed

Howlader P., Bhandari P., Chakraborty D., Clegg J. K., Mukherjee P. S., Inorg. Chem. 2020, 59, 15454–15459. PubMed

Han M., Luo Y., Damaschke B., Gómez L., Ribas X., Jose A., Peretzki P., Seibt M., Clever G. H., Angew. Chem. Int. Ed. 2016, 55, 445–449. PubMed

Kypr J., Kejnovská I., Bednářová K., Vorlíčková M., in Compr. Chiroptical Spectrosc. John Wiley & Sons, Ltd, Hoboken, New Jersey, USA: 2012, 2, pp. 575–586, 10.1002/9781118120392.ch17. DOI

Stow S. M., Causon T. J., Zheng X., Kurulugama R. T., Mairinger T., May J. C., Rennie E. E., Baker E. S., Smith R. D., McLean J. A., Hann S., Fjeldsted J. C., Anal. Chem. 2017, 89, 9048–9055. PubMed PMC

Gabelica V., Shvartsburg A. A., Afonso C., Barran P., Benesch J. L. P., Bleiholder C., Bowers M. T., Bilbao A., Bush M. F., Campbell J. L., Campuzano I. D. G., Causon T., Clowers B. H., Creaser C. S., De Pauw E., Far J., Fernandez‐Lima F., Fjeldsted J. C., Giles K., Groessl M., Hogan C. J., Hann S., Kim H. I., Kurulugama R. T., May J. C., McLean J. A., Pagel K., Richardson K., Ridgeway M. E., Rosu F., et al., Mass Spectrom. Rev. 2019, 38, 291–320. PubMed PMC

Frisch M. J., Trucks G. W., Schlegel H. B., Scuseria G. E., Robb M. A., Cheeseman J. R., Scalmani G., Barone V., Mennucci B., Petersson G. A., Nakatsuji H., Caricato M., Li X., Hratchian H. P., Izmaylov A. F., Bloino J., Zheng G., Sonnenberg J. L., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J. A. Jr., et al., Gaussian 09, Revision D.01., 2013, http://www.rsc.org/suppdata/c5/sc/c5sc02423d/c5sc02423d1.pdf.

Linnanto J., Korppi‐Tommola J., J. Phys. Chem. A 2004, 108, 5872–5882.

Schneider M., Grossi M. F., Gadara D., Spáčil Z., Babica P., Bláha L., J. Hazard. Mater. 2022, 424, 127447. PubMed

Gütz C., Hovorka R., Klein C., Jiang Q.‐Q., Bannwarth C., Engeser M., Schmuck C., Assenmacher W., Mader W., Topić F., Rissanen K., Grimme S., Lützen A., Angew. Chem. Int. Ed. 2014, 53, 1693–1698. PubMed

Schulte T. R., Holstein J. J., Clever G. H., Angew. Chem. Int. Ed. 2019, 58, 5562–5566. PubMed PMC

Wu K., Tessarolo J., Baksi A., Clever G. H., Angew. Chem. Int. Ed. 2022, 61, e202205725. PubMed PMC