Zn2+‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Abstract

AbstractThe gadolinium(III) complexes GdL1 and GdL2 were designed as Zn2+‐responsive bimodal magnetic resonance imaging (MRI) and fluorescence imaging probes. Upon binding to Zn2+ ions, GdL1 exhibits a bidentate or tridentate mode to form heterodinuclear GdL1Zn or heterotrinuclear (GdL1)2Zn, whereas GdL2 binds to the Zn2+ ion only in a bidentate mode to form (GdL2)2Zn. The gadolinium(III) complexes derived from both H3L1 and H3L2 exhibit remarkable interactions with human serum albumin (HSA) at both site I and site II, which result in significant enhancements of the relaxivity and remarkable improvements of T1‐weighted imaging contrast. In the presence of HSA, both the relaxivity (r1) and fluorescence exhibit 300 % enhancement with a clear blueshift of the fluorescence for GdL1Zn, which is ascribed to direct binding to HSA through the formation of a Zn–HSA coordination bond. In contrast, the presence of HSA induces smaller relaxivity increases for GdL1 (155 %), (GdL1)2Zn (183 %), GdL2 (192 %), and (GdL2)2Zn (181 %); these increases are ascribed to weaker hydrophobic interactions or stereospecificity with HSA. The contrast of T1‐weighted phantom MR images of these gadolinium(III) complexes in human serum (HS) is much improved relative to that in 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) buffer solutions.