Studies of the hydrophobic interaction between a pyrene - containing dye and a tetra-aza macrocyclic gadolinium complex

An in vivo and in vitro investigation of the hydrophobic interaction between HPTS and gadolinium(III)-complex of tetra-aza macrocyclic ligand HP-DO3A‡ (Gd(HP-DO3A)) is reported. UV-spectra at variable pH showed that the interaction is not influenced by the protonation state of HPTS. The data were accounted in terms of the presence of protonated and deprotonated species of HPTS and the formation of binary and ternary adducts with one and two Gd(III)-complexes, respectively. The X-ray solid state structures of adduct containing crystals (obtained at pH 4 and 9) showed that the pyrene ring is facing the tetraaza macrocyclic ring of Gd(III)-complex as previously suggested on the basis of 1H-NMR solution studies. The occurrence of the strong hydrophobic interaction was exploited to detect the in vivo distribution of Gd(HP-DO3A) in tumor-bearing mice, by assessing the changes in the fluorescent properties of the adduct (through fluorescence optical imaging). The co-presence of Gd(HP-DO3A) and HPTS enhances the fluorescent emission providing an indirect information on the in vivo distribution of the Gd(III)-complex. These findings may pave the way for novel applications in imaging guided surgery by bridging the pre-surgery MRI information to the in situ optical imaging detecti