Lanthanide(III) macrocyclic complexes as PARACEST agents for MRI and highly luminescent europium(III) phenanthroline derivatives for DNA detection
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The first chapter is focused on PARACEST (paramagnetic chemical exchange saturation transfer) agents. Lanthanide(III) complexes of 1,4,7,10-tetrakis(hydroxyethyl)-1,4,7,10-tetraazacyclododecane (THED) and 1s,4s,7s,10s-tetrakis(hydroxypropyl)-1,4,7,10-tetraazacyclododecane (S-THP) were studied as PARACEST agents. The CEST effect was observed at acidic and neutral pH which is related to the pK a of alcohol/water groups of complexes. Yb(S-THP) 3+ with the lowest pK a among the complexes studied demonstrates optimal CEST at pH 3.0 while Ce(S-THP) 3+ with the highest pK a demonstrates optimal CEST at neutral pH. The CEST spectra of the Eu(III), Ce(III) and Yb(III) complexes selectively respond to anions through outer- or inner- sphere interactions. These interactions can be identified by 1 H NMR, UV-vis and lanthanide luminescence spectroscopy. Ligands such as phosphate diester (DEP) that induce outersphere interaction with the complex mediate the CEST change and modulate the pK a of the alcohol groups which can be observed by NMR and the luminescence spectroscopy. In contrast, ligands such phosphate monoester (MP) directly binds to the metal center of the complexes to give rise to a new CEST peak and a similar pH dependent CEST effect. However, the CEST response of Yb(S-THP) 3+ was solely observed with anions through outersphere interaction. The CEST phantom image of Yb(S-THP) 3+ with phosphate diester (DEP) at acidic or neutral pH demonstrates the feasibility of the alcohol PARACEST agents for MRI applications. The second chapter is focused on luminescent lanthanide(III) probes for biomolecules. The design of Eu(III) complexed to phenanthroline derivatives is of our special interest for the phenanthroline group can be functionalized as a triplet-state photosensitizer for biomedical, biological, and bioorganic applications. In this chapter, the first example of lanthanide(III) complexes of DNA that incorporate a non-nucleoside phenanthroline building block directly into the DNA phosphate ester backbone on the bulge site was studied. To understand the luminescence spectroscopy of the Eu(III) complex of modified DNA, two phenanthroline derivatives 2,9-bis(hydroxylethylamide)-1,10-phenanthroline (PHENAE) and 2,9-bis(hydroxylpropylamide)-1,10-phenanthroline (PHENAP) were prepared. The direct excitation and sensitized spectra showed that the 1,10-phenanthroline can greatly enhance the luminescence of the complexes and the modified DNA. Therefore, it is feasible to incorporate a phenanthroline into the DNA backbone as a sensitizer for MR and optical applications.