Synthesis, novel crystal structure, and beta-amyloid binding property of Re(I) (tricarbonyl) EHIDA analogue

A neutral compound Re(CO)(3)(L) (L: 2-((2-(2,6-diethylphenylamino)-2-oxoethyl)(2-ethoxy-2-oxoethyl)amino)acetic acid, an IDA analogue) has been synthesized and evaluated for in vitro imaging probes of beta-amyloid (Abeta) aggregates. Results of X-ray measurement of Re(CO)(3)(L) demonstrated that the coordination mode of Re(CO)(3)(L) was different from that of classical Re/Tc(I) (tricarbonyl)-IDA analogues; the structure of Re(CO)(3)(L) was confirmed by means of infrared spectrum, HPLC-UV, TOF MS, and X-ray measurements (Cambridge Crystallographic Data Centre number is 732731): monoclinic P2(1)/c, a = 15.6636 (12) A, b = 10.9360 (8) A, c = 27.756 (2) A, alpha = 90.000 (0) degrees , beta = 90.783 (5) degrees , gamma = 90.000 (0) degrees , and Z = 8. The binding affinity for beta-amyloid plaques was assessed by in vitro binding assay using preformed synthetic Abeta((1-40)) aggregates. The neutral compound Re(CO)(3)(L) showed binding affinity to Abeta aggregates at micromolar level by fluorescence spectroscopy, and this work will encourage for further exploration of imaging agents labeled by (99m)Tc(CO)(3) (+) center as probes for beta-amyloid plaques in vivo.