Non‐Cytotoxic, Bifunctional Eu^III and Tb^III Luminescent Macrocyclic Complexes for Luminescence Resonant Energy‐Transfer Experiments

Abstract

A new macrocyclic ligand, L3, has been synthesised, based on the cyclen framework grafted with three phenacyl light-harvesting groups and a C5-alkyl chain bearing a carboxylic acid function as a potential linker for biological material. Acidity constants are determined by spectrophotometric titrations, as well as conditional stability constants for the resulting 1:1 complexes with trivalent lanthanide ions. The complexes have stabilities comparable to 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (dtma) complexes, with pLn approximately 12-13. Photophysical properties of the ligand and of the EuL3 and TbL3 complexes have been determined for both microcrystalline samples and solutions in water and acetonitrile. They point to the metal ion being present in an environment with axial symmetry derived from the C4 point group. The hydration number determined for TbL3 decreases with increasing pH value and becomes fractional at pH 7.5, which points to an equilibrium between two differently solvated species and probably to the participation of the deprotonated carboxylic acid chain in the complexation. The quantum yields in water (1.9% for EuIII, 3.4% for TbIII) are smaller than those for complexes with the symmetrically substituted parent macrocycle, but efficient luminescence resonant energy transfer (LRET) was observed when Cy5 dye was added to the solutions. Finally, the influence of the TbL3 complex on cell viability is tested on both malignant (5D10 mouse hybridoma, Jurkat human T leukaemia, MCF-7 human breast carcinoma) and non-malignant (Hacat human keratinocyte) cell lines. Cell viability after 24 h incubation at 37 degrees C with 500 microM TbL3 was >90% for all cell lines, except Jurkat (>70%). All of these properties make LnL3 complexes interesting potential probes for bioanalyses.

Multifunctional Hydroxyapatite Nanofibers and Microbelts as Drug Carriers

“…This relationship between the luminescence properties and extent of drug release has potential as a probe for monitoring or tracking the drug‐release process. Finally, to assess the potential use of the lanthanide ion (Ln 3+ ) for in vitro analyses, Ferrand and co‐workers tested the cytotoxicity of the Tb 3+ complex with respect to several cell lines 29. No significant difference was observed in cell proliferation in the absence or presence of permitted concentrations of Tb 3+ .…”

“…Finally, to assess the potential use of the lanthanide ion (Ln 3 + ) for in vitro analyses, Ferrand and co-workers tested the cytotoxicity of the Tb 3 + complex with respect to several cell lines. [29] No significant difference was observed in cell proliferation in the absence or presence of permitted concentrations of Tb 3 + . The test results, combined with the non-toxicity for several cell lines that has been demonstrated for Tb 3 + , points to potential in vitro applications of Ln 3 + .…”

Luminescence Resonance Energy Transfer in Heterodinuclear LnIII Complexes for Sensing Biologically Relevant Anions

“…(1) Luminescence resonance energy transfer between Ln III ions in aqueous solution has focused primarily on systems that form dinuclear complexes either through self-assembly of two mononuclear Ln III complexes, usually with bridging hydroxide ligands, or on ligands that bind two Ln III ions. [21,30,[42][43][44][45] In addition, LRET has been applied to mapping metal ion binding sites of biomolecules. [46] In particular, Ln III are good Ca II surrogates and have been used to study multisite calcium binding proteins such as Troponin-C, [47] parvalbumin, [48,49] and thermolysin.…”

Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents

“…The primary objective of such derivatization of the macrocycle is to add pendant arms that help define the binding site and act as a means of controlling the properties of the resulting metal complexes. Derivatization, typically at the nitrogen centres, attaches additional functional groups such as carbonyl, ester, alcohol amine and amide functionalities [ 12 , 13 , 14 , 15 ] that increase the number and type of donor atoms available for chelation to the central metal ion. This is particularly important for the lanthanide ions, which have high coordination numbers (9–10) and a preference for hard donor atoms such as nitrogen or oxygen.…”