1 research outputs found
Effect of Lanthanide Complex Structure on Cell Viability and Association
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 (ED<sub>50</sub> > 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