NDLI: Enhanced kinetic stability of $[Pd_{2}L_{4}]^{4+}$ cages through ligand substitution

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mcneill, Samantha M. Crowley, James D. Giles, Gregory I. Preston, Dan Lewis, James E. M.
Description	Author Affiliation: Preston D ( Department of Chemistry, University of Otago, PO Box 56, Dunedin, New Zealand. jcrowley@chemistry.otago.ac.nz.); McNeill SM ( Department of Pharmacology and Toxicology, University of Otago, PO Box 56, Dunedin, New Zealand.); Lewis JE ( Department of Chemistry, University of Otago, PO Box 56, Dunedin, New Zealand. jcrowley@chemistry.otago.ac.nz.); Giles GI ( Department of Pharmacology and Toxicology, University of Otago, PO Box 56, Dunedin, New Zealand.); Crowley JD ( Department of Chemistry, University of Otago, PO Box 56, Dunedin, New Zealand. jcrowley@chemistry.otago.ac.nz.)
Abstract	There is considerable interest in exploiting metallosupramolecular cages as drug delivery vectors. Recently, we developed a $[Pd_{2}L_{4}]^{4+}$ cage capable of binding two molecules of cisplatin. Unfortunately, this first generation cage was rapidly decomposed by common biologically relevant nucleophiles. In an effort to improve the kinetic stability of these cage architectures here we report the synthesis of two amino substituted tripyridyl 2,6-bis(pyridin-3-ylethynyl)pyridine (tripy) ligands (with amino groups either in the 2-(2A-tripy) or 3-(3A-tripy) positions of the terminal pyridines) and their respective $[Pd_{2}(L_{tripy})_{4}]^{4+}$ cages. These systems have been characterised by $^{1}H,$ $^{13}C$ and DOSY NMR spectroscopies, high resolution electrospray mass spectrometry, elemental analysis and, in one case, by X-ray crystallography. It was established, using model palladium(II) N-heterocyclic carbene (NHC) probe complexes, that the amino substituted compounds were stronger donor ligands than the parent system (2A-tripy > 3A-tripy > tripy). Competition experiments with a range of nucleophiles showed that these substitutions lead to more kinetically robust cage architectures, with $[Pd_{2}(2A-tripy)_{4}]^{4+}$ proving the most stable. Biological testing on the three ligands and cages against A549 and MDA-MB-231 cell lines showed that only $[Pd_{2}(2A-tripy)_{4}]^{4+}$ exhibited any appreciable cytotoxicity, with a modest $IC_{50}$ of 36.4 ± 1.9 μM against the MDA-MB-231 cell line. Unfortunately, the increase in kinetic stability of the $[Pd_{2}(L_{tripy})_{4}]^{4+}$ cages was accompanied by loss of cisplatin-binding ability.
ISSN	14779226
Issue Number	19
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-05-10
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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