New 1,3-Disubstituted Benzo[ h]Isoquinoline Cyclen-Based Ligand Platform: Synthesis, Eu 3+ Multiphoton Sensitization and Imaging Applications

Molecules. 2020 Dec 24;26(1):58. doi: 10.3390/molecules26010058.

Abstract

The development of lanthanide-based luminescent probes with a long emission lifetime has the potential to revolutionize imaging-based diagnostic techniques. By a rational design strategy taking advantage of computational predictions, a novel, water-soluble Eu3+ complex from a cyclen-based ligand bearing 1,3-disubstituted benzo[h]isoquinoline arms was realized. The ligand has been obtained overcoming the lack of reactivity of position 3 of the isoquinoline moiety. Notably, steric hindrance of the heteroaromatic chromophore allowed selective and stoichiometry-controlled insertion of two or three antennas on the cyclen platform without any protection strategy. The complex bears a fourth heptanoic arm for easy conjugation to biomolecules. This new chromophore allowed the sensitization of the metal center either with one or two photons excitation. The suitability as a luminescent bioprobe was validated by imaging BMI1 oncomarker in lung carcinoma cells following an established immunofluorescence approach. The use of a conventional epifluorescence microscope equipped with a linear structured illumination module disclosed a simple and inexpensive way to image confocally Ln-bioprobes by single photon excitation in the 350-400 nm window, where ordinary confocal systems have no excitation sources.

Keywords: benzoisoquinoline; bioprobe; cyclen; europium complex; structured illumination microscopy.

MeSH terms

  • Algorithms
  • Chemistry Techniques, Synthetic
  • Cyclams / chemical synthesis
  • Cyclams / chemistry*
  • Europium
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry*
  • Ligands
  • Luminescence
  • Luminescent Measurements
  • Models, Molecular
  • Models, Theoretical
  • Molecular Structure
  • Photochemical Processes

Substances

  • Cyclams
  • Isoquinolines
  • Ligands
  • Europium
  • cyclen