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Effect of lanthanide complex structure on cell viability and association.

Peterson KL, Dang JV, Weitz EA, Lewandowski C, Pierre VC - Inorg Chem (2014)

Bottom Line: A systematic study of the effect of hydrophobicity and charge on the cell viability and cell association of lanthanide metal complexes is presented.Only the hexyl-substituted complex reduced cell viability to 60% in the presence of 100 μM complex.Surprisingly, the hydrophobic moieties did not increase cell association in comparison to the hydrophilic amino acid derivatives.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Minnesota , Minneapolis, Minnesota 55455, United States.

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.

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Chemical Structures of Derivatives of [Tb-1] withVarying Charged and Hydrophobicitiesa
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cht2: Chemical Structures of Derivatives of [Tb-1] withVarying Charged and Hydrophobicitiesa


Effect of lanthanide complex structure on cell viability and association.

Peterson KL, Dang JV, Weitz EA, Lewandowski C, Pierre VC - Inorg Chem (2014)

Chemical Structures of Derivatives of [Tb-1] withVarying Charged and Hydrophobicitiesa
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4060611&req=5

cht2: Chemical Structures of Derivatives of [Tb-1] withVarying Charged and Hydrophobicitiesa
Bottom Line: A systematic study of the effect of hydrophobicity and charge on the cell viability and cell association of lanthanide metal complexes is presented.Only the hexyl-substituted complex reduced cell viability to 60% in the presence of 100 μM complex.Surprisingly, the hydrophobic moieties did not increase cell association in comparison to the hydrophilic amino acid derivatives.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Minnesota , Minneapolis, Minnesota 55455, United States.

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.

Show MeSH
Related in: MedlinePlus