Effect of Lanthanide Complex Structure on Cell Viability and Association

Abstract

A systematic study of the effect of hydrophobicity and charge on the cell viability and cell association of lanthanide metal complexes is presented. The terbium luminescent probes feature a macrocyclic polyaminocarboxylate ligand (DOTA) in which the hydrophobicity of the antenna and that of the carboxyamide pendant arms are independently varied. Three sensitizing antennas were investigated in terms of their function in vitro: 2-methoxyisophthalamide (IAM(OMe)), 2-hydroxyisophthalamide (IAM), and 6-methylphenanthridine (Phen). Of these complexes, Tb-DOTA-IAM exhibited the highest quantum yield, although the higher cell viability and more facile synthesis of the structurally related Tb-DOTA-IAM(OMe) platform renders it more attractive. Further modification of this latter core structure with carboxyamide arms featuring hydrophobic benzyl, hexyl, and trifluoro groups as well as hydrophilic amino acid based moieties generated a family of complexes that exhibit high cell viability (ED50 > 300 μM) regardless of the lipophilicity or the overall complex charge. Only the hexyl-substituted complex reduced cell viability to 60% in the presence of 100 μM complex. Additionally, cellular association was investigated by ICP-MS and fluorescence microscopy. Surprisingly, the hydrophobic moieties did not increase cell association in comparison to the hydrophilic amino acid derivatives. It is thus postulated that the hydrophilic nature of the 2-methoxyisophthalamide antenna (IAM(OMe)) disfavors the cellular association of these complexes. As such, responsive luminescent probes based on this scaffold would be appropriate for the detection of extracellular species.

Synthesis and effect of a new Terbium gibberellic complex on the histopathological alteration induced by Gibberellic acid on liver and kidney of mice Mus musculus

“…GA-Tb complex-treated group showed improvement in the expression (c). [29,75] Moreover, Lanthanides can protect the liver against abnormalities induced by xenobiotics by blocking Kupffer cells infiltration [23,[76][77][78] or suppress the elevation of TNF levels by increasing IL-6 levels. Inhibition of TNFR2 expression was observed in kidney sections treated with Gibberellic acid (e), whereas viability of the kidney tissue return to immunostaining of TNFR2 in GA-Tb complex-treated group (f) and more intense of TNFR2 were noted as compared to control (f) [Colour figure can be viewed at wileyonlinelibrary.com] of cell membrane in tubules and glomerulus.…”

A Practical Route for the Preparation of 1,4,7-Triazacyclononanyl Diacetates with a Hydroxypyridinonate Pendant Arm

“…There has been considerable interest in the synthesis and coordination chemistry of polyazacycles with coordinating pendant arms because of their potential use in applications such as magnetic resonance imaging (MRI) contrast agents [1,2], positron emission tomography (PET) [3,4], luminescence probes [5,6,7,8], catalysis [9], and so on. Among the polyazacycle derivatives, tetraazamacrocycles with acetate side chains have received the most attention owing to their strong chelating properties and higher selectivity toward di- or trivalent metal ions [10,11,12,13].…”

Eu(iii) and Tb(iii) complexes of 6-fold coordinating ligands showing high affinity for the hydrogen carbonate ion: a spectroscopic and thermodynamic study

“…Another important factor that must not be neglected when the compounds are used in in vitro experiments is the impact of the hydrophobicity and charge of lanthanide metal complexes on the cell viability and cell association, 12 including their membrane permeability. [13][14][15][16][17] The in vitro localization of the optical probe affects the type of analytes that can be detected.…”

“…For example, a probe with an extracellular location is particularly suitable to detect analytes such as group I ions, polysaccharides, hormones, or other signaling molecules. 12 Another crucial aspect to consider is the selectivity of the optical response towards a particular analyte. In this context, the modulation of the structure of the side pendants within the DO3A-based complexes gave the best results when serum proteins and biological relevant ions are taken into account.…”