Deciphering the Metal Speciation in Low‐Molecular‐Weight Complexes by IMS‐MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates

Abstract

The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2‐di‐aminoethane functionalized with imidazole and phenolate and has good intrinsic anti‐superoxide, antioxidant and anti‐inflammatory activities in lipopolysaccharide (LPS)‐activated intestinal epithelial HT29‐MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry‐mass spectrometry (IMS‐MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co‐13C6 analogue.

A New Manganese Superoxide Dismutase Mimetic Improves Oxaliplatin-Induced Neuropathy and Global Tolerance in Mice

“…[ 12 , 32 ]. The parent MnSOD mimic Mn1 was included as a reference [ 13 , 43 ]. The results provided as k McCF are presented in Table 1 .…”

“…We designed and synthesized the first Pt(IV) complexes as covalent conjugates between oxaliplatin and MnSOD mimics derived from complex Mn1 (MAG) [ 13 , 31 , 43 ] to evaluate them for their antitumoral activity and effect on oxaliplatin-induced peripheral neuropathy. Three Mn-uncoordinated Pt(IV) conjugate OxPt-x-1C1A (x = 1OH,1,2) were prepared and characterized.…”

Towards multimodal cellular imaging: optical and X-ray fluorescence

“…This study highlights the importance of evaluating the impact of a fluorescence tag on the biological behaviour of a metal complex/therapeutic by demonstrating that tagging with the fluorophores significantly modulated the cellular distribution of manganese compared to the untagged parent complex. 96…”

“…This study highlights the importance of evaluating the impact of a fluorescence tag on the biological behaviour of a metal complex/therapeutic by demonstrating that tagging with the fluorophores significantly modulated the cellular distribution of manganese compared to the untagged parent complex. 96 6.1.4 Antibiotics. Organic therapeutics, including most antibiotics, typically cannot be detected by either XFM or OFM, but the addition of an optical fluorescent reporter and heavy atom at inactive sites on the compound provides an avenue to image with one or both modalities.…”