Synthesis and tumour cell uptake studies of gadolinium(III)–phosphonium complexes

Abstract

The synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported. Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. The in vitro cytotoxicity of all complexes was determined to be low at therapeutically-relevant concentrations. Selected Gd(III) complexes are potential candidates for further investigation as theranostic agents.

Using ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells

“…Gd might be coordinated with ligands present in the incubation medium, for example, glucose [ 77 ]. To achieve specific delivery of Gd for neutron capture therapy or imaging applications, nanocomposites are used based on chitosan nanoparticles [ 78 ], liposomes [ 79 ], dendrimeric constructs [ 80 ], and single-walled carbon nanotubes [ 81 ], along with the study of new complexing agents [ 82 ].…”

Fluorescently Labeled Gadolinium Ferrate/Trigadolinium Pentairon(III) Oxide Nanoparticles: Synthesis, Characterization, In Vivo Biodistribution, and Application for Visualization of Myocardial Ischemia–Reperfusion Injury

“…The synthesis of such complexes is usually low-yield and, in addition, requires multi-step synthetic approaches [ 18 ]. Despite better contrasting effect and lower toxicity of these second-generation gadolinium compounds, compared to gadolinium chelates [ 19 ], their synthesis still necessitates the use of unsafe solvents requiring complex and expensive purification [ 20 ]. The information about the techniques of gadolinium ferrites synthesis is scarce.…”

Significant cell uptake of Gd(iii)-diphenylphosphoryl-diphenylphosphonium complexes: evidence for a new conformationally-dependent tumour cell targeting vector

“…24 We have previously investigated a series of Gd(III)-triphenylphosphonium and -arsonium derivatives for their theranostic potential and synthesised a series of related analogues to probe the impact that the group 15 element and linker groups had on tumour cell uptake and selectivity. [9][10][11]25,26 Herein we report the synthesis of a novel series of Gd(III)-diphenylphosphoryl-diphenylphosphonium complexes and examine their uptake in human glial (SVG p12) and human glioblastoma (T98G) cells.…”

“…Alternatively, the bromomethyl phosphonium salts (10)(11)(12) were converted to the primary amine (via their azide intermediates), which could then be coupled to the tertbutyl triester of DOTA using the peptide-coupling agent HATU and N-methylmorpholine (NMM). 25 All the tert-butyl pro-ligands were deprotected with TFA and purified by means of reverse-phase HPLC to give the required free ligands. Complexation of the Gd 3+ ion was achieved by stirring the free ligand in a suspension of Gd 2 O 3 in H 2 O to afford the target Gd(III) complexes 1-6 in high yield and purity.…”

“…When compared to the parent Gd(III)-triphenylphosphonium complexes, [9][10][11]25 it is clear that complexes 1-3 and 4-6, respectively, Scheme 1 The synthesis of Gd(III)-diphenylphosphoryl-diphenylphosphonium complexes (1-6).…”