Synthesis and optical properties of macrocyclic lanthanide(III) chelates as new reagents for luminescent biolabeling

Org Biomol Chem. 2012 Nov 14;10(42):8509-23. doi: 10.1039/c2ob26311d. Epub 2012 Sep 25.

Abstract

The convenient and efficient synthesis of two macrocyclic ligands (15- and 18-membered) based on a dipyrido-6,7,8,9-tetrahydrophenazine (dpqc) or 2,2':6',2''-terpyridine (tpy) heterocycle and a DTTA (diethylenetriaminetriacetic acid) skeleton is described. In these ligands the DTTA skeleton contains an additional extracyclic functionality (NH(2) group) suitable for covalent attachment to bioactive molecules. These octa- and nonadentate ligands form very stable and luminescent neutral lanthanide complexes in aqueous solutions at physiological pH. The corresponding Eu(III) and Tb(III) complexes are characterized by a maximum absorption wavelength compatible with nitrogen laser excitation (337 nm) and attractive lifetimes and quantum yields. Further introduction of a maleimide bioconjugatable handle in the Eu(III) complexes was investigated and a valuable luminescence brightness above 1500 dm(3) mol(-1) cm(-1) at 337 nm was obtained with the corresponding Eu(III) tpy-derivative. Finally, these two luminescent chelates were grafted onto thiol residues of a model antibody (Mab GSS11) without loss of their luminescent properties.

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry*
  • Lanthanoid Series Elements / chemical synthesis
  • Lanthanoid Series Elements / chemistry*
  • Luminescent Agents / chemical synthesis
  • Luminescent Agents / chemistry*
  • Macrocyclic Compounds / chemical synthesis
  • Macrocyclic Compounds / chemistry*
  • Maleimides / chemical synthesis
  • Maleimides / chemistry
  • Pentetic Acid / analogs & derivatives
  • Pentetic Acid / chemical synthesis
  • Pentetic Acid / chemistry
  • Phenazines / chemical synthesis
  • Phenazines / chemistry
  • Pyridines / chemical synthesis
  • Pyridines / chemistry

Substances

  • (2,2'-6',2'')-terpyridine
  • Antibodies, Monoclonal
  • Chelating Agents
  • Lanthanoid Series Elements
  • Luminescent Agents
  • Macrocyclic Compounds
  • Maleimides
  • Phenazines
  • Pyridines
  • diethylenetriaminetetraacetic acid
  • maleimide
  • Pentetic Acid