The project is funded by Bulgarian National Science Fund – grant KP-N29/12
Project overview
The current project aims at the design and development of Monomolecular Bifunctional Imaging Probes (MoBIPs) as the main unit of new bimodal sensors for diagnostic imaging of various disease states (Fig. 1). The main objective is to obtain highly efficient imaging probes consisting of strategically selected fluorescent dye and a macrobicyclic chelator that will enable the simultaneous application of optical and nuclear imaging modalities by the use of one and the same molecule. The successful chemical design and synthesis of the new and superior MoBIPs will initiate an interdisciplinary research topic involving biologists, nuclear chemists, and medical doctors with direct application in modern medicine and diagnostics.
Figure 1. Concept for design of bimodal sensors for diagnostic imaging
The radiotracer employed in our MoBIPs consists of a sarcophagine cage (Fig. 2A) that has been proved as the best chelator for Cu(II) ions being superior to many other well-studied acyclic or polyaza-macrocyclic chelators, like DOTA, TETA, NOTA, and their derivatives. Among the classes of fluorescent dyes, we have chosen to use the naphthalene- and perylene-based derivatives due to their exceptionally high absorptivity, bright fluorescence, excellent photostability and tunable absorbance and emission wavelengths. Introducing electron-donor substituents at the peri-positions leads to formation of a push-pull system with desired optical properties (Fig. 2B).
Figure 2. A) Molecular structure of the sarcophagine cage with substituents at the side amine groups; B) General structures of the target dyes
The main project objectives are formulated as follows:
- Synthesis and characterization of tunable fluorescent dyes covering broad spectral region, and suitably modified sarcophagine cages
- Synthesis of MoBIPs by linking the sarcophagine cages with the fluorescent dye in several possible ways and characterization of their structural, optical, and physicochemical properties
- Spectroscopic study of the effects of the metal ions, environment (solvent, acidity, temperature) and presence of biomolecules on the optical properties of the new MoBIPs and their metal complexes
- Detailed experimental estimation of the thermodynamic and kinetic properties of the formed Cu-complexes of the new MoBIPs and selection of the best candidates to be provided for further bioconjugation and/or analytical and biological tests