Stimuli-responsive Pd 2L 4 metallosupramolecular cages: Towards targeted cisplatin drug delivery

James E.M. Lewis, Emma L. Gavey, Scott A. Cameron, James D. Crowley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

294 Citations (Scopus)


Metallosupramolecular cages are an emerging, but as of yet relativity unexplored, drug delivery vector. Herein we show that discrete dipalladium(ii) molecular cages of the formula [Pd 2L 4](X) 4 can be quantatively self-assembled from a simple tripyridyl ligand (2,6-bis(pyridin-3-ylethynyl)pyridine) and [Pd(CH 3CN) 4](X) 2 (X = BF 4 - or SbF 6 -). The cages have been fully characterised using 1H, 13C and DOSY NMR spectroscopy, elemental analysis, IR spectroscopy, and high resolution electrospray mass spectrometry (HR-ESMS). Additionally, the molecular structure of the [Pd 2L 4](SbF 6) 4 cage was confirmed unequivocally using X-ray diffraction. These [Pd 2L 4](X) 4 cages are stimuli-responsive and can be reversibly disassembled/reassembled upon the addition/removal of suitable competing ligands. The central cavities of the [Pd 2L 4](X) 4 cages are lined with four hydrogen bond accepting pyridine units which enable the encapsulation of two cisplatin molecules within the metallosupramolecular architecture through hydrogen bonding interactions between the cage and the amine ligands of the cisplatin guest. The structure of the [Pd 2L 4⊃(cisplatin) 2](BF 4) 4 host-guest adduct has been confirmed by 1H NMR spectroscopy, HR-ESMS and X-ray crystallography. Additionally we have demonstrated that the cage-cisplatin host-guest adduct can be quantatively disassembled upon the addition of a competing ligand, releasing the cisplatin guest. This is the first crystallographically characterised example of a discrete metallosupramolecular cage encapsulating an FDA-approved inorganic drug molecule. This host-guest chemistry could open the way to relatively unexplored methods of drug delivery, which circumvent the malicious side effects and drug resistance associated with cisplatin and other anticancer therapeutics.

Original languageEnglish
Pages (from-to)778-784
Number of pages7
JournalChemical Science
Issue number3
Publication statusPublished - Mar 2012

ASJC Scopus subject areas

  • Chemistry(all)


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