Application of X-ray absorption and X-ray fluorescence techniques to the study of metallodrug action

Lovett, James; Harris, Hugh H.

doi:10.1016/j.cbpa.2020.12.004

Cited by 17 publications

(11 citation statements)

References 53 publications

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“…The high quantities of zinc in cell nuclei enable it to be easily identified in XFM studies. [19] The Ir complexes were taken up into the cells, while control experiments showed no signal for Ir in untreated cells (data not shown). The cellular uptake of 5 d was consistently observed for both cell lines as indicated by the relatively similar Zn/Ir elemental concentration ratio.…”

Section: Resultsmentioning

confidence: 90%

Triazolyl‐Functionalized N‐Heterocyclic Carbene Half‐Sandwich Compounds: Coordination Mode, Reactivity and in vitro Anticancer Activity

et al. 2021

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We report investigations on the anticancer activity of organometallic [M II/III (η 6 -p-cymene/η 5 -pentamethylcyclopentadienyl)] (M = Ru, Os, Rh, and Ir) complexes of N-heterocyclic carbenes (NHCs) substituted with a triazolyl moiety. Depending on the precursors, the NHC ligands displayed either mono-or bidentate coordination via the NHC carbon atom or as N,Cdonors. The metal complexes were investigated for their stability in aqueous solution, with the interpretation supported by density functional theory calculations, and reactivity to biomolecules. In vitro cytotoxicity studies suggested that the nature of both the metal center and the lipophilicity of the ligand determine the biological properties of this class of compounds. The Ir III complex 5 d bearing a benzimidazolederived ligand was the most cytotoxic with an IC 50 value of 10 μM against NCI-H460 non-small cell lung carcinoma cells. Cell uptake and distribution studies using X-ray fluorescence microscopy revealed localization of 5 d in the cytoplasm of cancer cells.

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Section: Resultsmentioning

confidence: 90%

Triazolyl‐Functionalized N‐Heterocyclic Carbene Half‐Sandwich Compounds: Coordination Mode, Reactivity and in vitro Anticancer Activity

et al. 2021

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“…Cryo-electron tomography 318 and optical fluorescence microscopy (including super-resolution techniques 319 and FRET-or lifetime-based imaging/spectroscopy 320 ) can provide insights into the structure and dynamics of intracellular macromolecules and complexes with extremely high spatial resolution, down to the sub-nanometer range, which is not accessible to an ensemble-based methodology like NMR spectroscopy. Other complementary cell-based imaging approaches include mass spectrometry imaging 321 and X-ray fluorescence microscopy, 322 which provide the spatial distribution of cellular metabolites and metal ions, respectively (integration of in-cell NMR with the latter was shown by Luchinat and Banci 323 ).…”

Section: Future Perspectivesmentioning

confidence: 99%

Radio Signals from Live Cells: The Coming of Age of In-Cell Solution NMR

2022

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A detailed knowledge of the complex processes that make cells and organisms alive is fundamental in order to understand diseases and to develop novel drugs and therapeutic treatments. To this aim, biological macromolecules should ideally be characterized at atomic resolution directly within the cellular environment. Among the existing structural techniques, solution NMR stands out as the only one able to investigate at high resolution the structure and dynamic behavior of macromolecules directly in living cells. With the advent of more sensitive NMR hardware and new biotechnological tools, modern in-cell NMR approaches have been established since the early 2000s. At the coming of age of in-cell NMR, we provide a detailed overview of its developments and applications in the 20 years that followed its inception. We review the existing approaches for cell sample preparation and isotopic labeling, the application of in-cell NMR to important biological questions, and the development of NMR bioreactor devices, which greatly increase the lifetime of the cells allowing real-time monitoring of intracellular metabolites and proteins. Finally, we share our thoughts on the future perspectives of the in-cell NMR methodology.

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“…Last but not least, X-ray absorption spectroscopy (XAS) can be used to quantify the relative content of metal complexes directly in cells prepared for X-ray fluorescence microscopy (XFM) (see below) [41, 79,80] or in whole-cell pellets (freeze-dried) [79]. Note that applications of XAS and XFM in bioinorganic research have been reviewed recently [81].…”

Section: Detection In Cellsmentioning

confidence: 99%