Lant, E C; Jadhav, A C; Sumeray, A; Trindade, G F; Craciunescu, L; Prentice, A W; Wolny, J A; Grewal, J S; Dallmann, R; Clarkson, G J; Dixon, A M; Schünemann, V; Gilmore, I S; Paterson, M J; Harkiolaki, M; Sadler, P J (2026) In Situ Lipid Interactions of an Anticancer Metal Complex. Inorganic Chemistry, 65 (12). pp. 6367-6372. ISSN 0020-1669

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Abstract

Surprisingly, catalytic half-sandwich Rh(III) anticancer complexes exhibit intense luminescence in cancer cells, with localization dependent on substituents on a chelated phenylazopyridine ligand. Phenylazopyridine itself, a widely-used anti-infective drug, is non-emissive. Density Functional Theory (DFT) modelling of supramolecular adducts revealed strong hydrophobic and polar interactions with membrane phospholipids. The penetration of complexes into glycerophosporylcholine lipids of a model tissue was observed by secondary ion mass spectrometry (SIMS). The ability of these complexes to destroy the ultrastructure of cells even at low doses, was revealed by correlated super resolution fluorescence microscopy and synchrotron soft X-ray tomography, using human lung cancer cells rapidly frozen (cryofixed) to preserve their ultra-structure in a near-native state, as well as the coordination environment of the complexes. Time-dependent-DFT calculations suggested that the emissive state is ceantered on the chelated ligand. Intact and fragmented Rh complex as well as phosphorylcholine fragments were co-located deep into a model tissue by SIMS depth-profiling using a high-mass-accuracy Orbitrap detector. Ground and excited state correlative metallomics studies such as these provide insights into novel mechanisms of action of bioactive metal complexes.

Item Type:	Article
Keywords:	anticancer, metal complex, OrbiSIMS
Subjects:	Nanoscience > Surface and Nanoanalysis
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1021/acs.inorgchem.6c00104
Last Modified:	19 Oct 2026 14:23
URI:	https://eprintspublications.npl.co.uk/id/eprint/10567