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Non-statistical assembly of multicomponent [Pd2ABCD] cages


Self-assembled hosts, inspired by biological receptors and catalysts, show application potential in sustainable synthesis, energy conversion and medicine. Implementing multiple functionalities in the form of distinguishable building blocks, however, is difficult without risking narcissistic self-sorting or a statistical mess. Here we report a systematic series of integratively self-assembled heteroleptic cages in which two square-planar PdII cations are bridged by four different bis-pyridyl ligands, A, B, C and D, via synergistic effects to exclusively form a single isomer—the lantern-shaped cage [Pd2ABCD]. This self-sorting goal—forming just one out of 55 possible structures—is reached under full thermodynamic control and can be realized progressively (by combining progenitors, such as [Pd2A2C2] with [Pd2B2D2]), directly from ligands and PdII cations or by mixing all four corresponding homoleptic cages. The rational design of complex multicomponent assemblies that enables the modular incorporation of diverse chemical moieties will advance their applicability in functional nanosystems.

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Fig. 1: Self-assembly of heteroleptic multicomponent cage [Pd2ABCD]4+ from four chemically different ligands.
Fig. 2: X-ray crystal structures of heteroleptic multicomponent cages with two or three different ligands.
Fig. 3: Characterization of heteroleptic multicomponent cage [Pd2ABCD]4+.
Fig. 4: Possible cage isomers and comparison of crystal structures of [Pd2ABCD] and [Pd2ABD4C].
Fig. 5: Thermodynamic analysis of cage isomers, competition experiments and sequential formation of [Pd2ABCD].

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Data availability

Crystallographic data for the structures reported in this paper have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under the deposition numbers 2207621, trans-[Pd2A2B2](BF4)4; 2285849, [Pd2B2CD1](BF4)4; 2207623, [Pd2A2CD](BF4)4; 2285847, [Pd2B2D4C](BF4)4; 2285846, [Pd2ABCD](BF4)4; 2207626, [Pd2AB0CD](BF4)4; 2207627, [Pd2ABD4C](BF4)4; 2207628, [Pd2ABD2D](BF4)4; and 2285848, [Pd2ABCD2](BF4)4. Copies of these data can be obtained free of charge via All other data supporting the findings of this study are available within the Article and its Supplementary Information, or from the corresponding author upon reasonable request. Source data are provided with this paper.


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We thank the European Research Council (ERC Consolidator Grant 683083, RAMSES) for financial support. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy EXC 2033 ‘RESOLV’, project number 390677874, and GRK2376 ‘Confinement‐Controlled Chemistry’, project number 331085229. We thank B. Chen, J. Tessarolo, A. Platzek, K. Ebbert and S. Hasegawa for providing ligands and L. Schneider for ESI mass spectra measurements. We thank J. J. Holstein for helpful suggestions on the crystallographic data analysis.

Author information

Authors and Affiliations



K.W. and G.H.C. conceived the project and wrote the manuscript together with E.B.; K.W. performed the experiments and analysed the data. A.B. provided ion mobility mass measurements. K.W. collected the X-ray single-crystal data and refined the crystal structures.

Corresponding author

Correspondence to Guido H. Clever.

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The authors declare no competing interests.

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Peer review information

Nature Chemistry thanks Xiaopeng Li and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–308 and Tables 1–9.

Supplementary Data 1

Crystallographic data for trans-[Pd2A2B2](BF4)4 (CCDC reference 2207621).

Supplementary Data 2

Crystallographic data for [Pd2B2CD1](BF4)4 (CCDC reference 2285849).

Supplementary Data 3

Crystallographic data for [Pd2A2CD](BF4)4 (CCDC reference 2207623).

Supplementary Data 4

Crystallographic data for [Pd2B2D4C](BF4)4 (CCDC reference 2285847).

Supplementary Data 5

Crystallographic data for [Pd2ABCD](BF4)4 (CCDC reference 2285846).

Supplementary Data 6

Crystallographic data for [Pd2AB0CD](BF4)4 (CCDC reference 2207626).

Supplementary Data 7

Crystallographic data for [Pd2ABD4C](BF4)4 (CCDC reference 2207627).

Supplementary Data 8

Crystallographic data for [Pd2ABD2D](BF4)4 (CCDC reference 2207628).

Supplementary Data 9

Crystallographic data for [Pd2ABCD2](BF4)4 (CCDC reference 2285848).

Source data

Source Data Fig. 2

HR-ESI-MS of cage [Pd2ABCD]4+.

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Wu, K., Benchimol, E., Baksi, A. et al. Non-statistical assembly of multicomponent [Pd2ABCD] cages. Nat. Chem. 16, 584–591 (2024).

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