Fluorescence/MRI sensing of zinc with water-soluble porphyrin molecular platform

INOR 111

Xiao-an Zhang, xiaoanz@mit.edu1, Katherine S. Lovejoy, lovejoy@mit.edu1, Alan Jasanoff2, and Stephen J. Lippard1. (1) Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg 18-463, Cambridge, MA 02139, (2) Departments of Nuclear Science & Engineering, Brain & Cognitive Sciences and Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139
To study in a non-invasive manner the physiological roles of zinc ion at a molecular level in intact biological systems, and to develop diagnostic modalities for diseases related to disruption of zinc homeostasis, we devised a molecular platform for dual-function fluorescence/MRI sensing of mobile zinc. Zinc-selective binding units were strategically attached to a water-soluble porphyrin template. The metal-free form (1) is fluorescent and has certain superior physical properties compared to earlier generation zinc sensors. Included are emission in the red and near infrared (NIR) regions of the spectrum with a large Stokes shift. The fluorescence intensity of 1 increases by greater than 10-fold upon zinc binding. The construct is highly selective for zinc versus other divalent metal ions and is relatively pH-insensitive within the biologically relevant pH window. The manganese(III) derivative 2 switches the function of the molecule to generate an MRI contrast agent (CA). In the presence of zinc, the relaxivity of 2 in aqueous solution is significantly altered, making it a promising zinc MRI sensor. Both 1 and 2 efficiently enter live cells and can image intracellular zinc by either fluorescence or MR, respectively. This work was support by a grant from the National Institute of General Medical Sciences.