First example of well-characterized Re and 99mTc tricarbonyl complexes of ciprofloxacin and norfloxacin in the development of infection-specific imaging agents

Aiming at the development of 99mTc-based infection-specific imaging agents, the synthesis and characterization of rhenium and technetium-99m tricarbonyl complexes with derivatized ciprofloxacin and norfloxacin is hereby reported. The ligands were prepared by coupling the tridentate chelator picolylamino-N,N-diacetic acid (PADA) with the piperazinyl (NH) nitrogen of ciprofloxacin or norfloxacin, through the employment of the PADA anhydride. The corresponding rhenium complexes were synthesized using the fac-[NEt4]2[ReBr3(CO)3] precursor and were fully characterized by elemental analysis and NMR spectroscopy. X-ray crystallography of the ciprofloxacin complex showed that the geometry about rhenium is distorted octahedral defined by the NNO donor atom set of the tridentate chelator and the three carbonyl groups. The analogous technetium-99m complexes were prepared quantitatively through the use of the fac-[99mTc(H2O)3(CO)3]+ precursor and their structure was established by comparative HPLC studies using the well-characterized rhenium complexes as reference. Preliminary studies with the technetium-99m complexes showed high bacterial uptake in vitro.

Two new fac-[Re(CO)3]+ tricarbonyl complexes bearing the fluoroquinolone antibiotics ciprofloxacin and norfloxacin as active pharmacophores were successfully synthesized through the employment of the anhydride of picolylamino-N,N-diacetic acid (PADA). The complexes were fully characterized through IR, NMR spectroscopies and X-ray crystallography and were used as references for the characterization of their 99mTc analogues which represent the first example of well-defined fluoroquinolone complexes as infection specific imaging agents.Figure optionsDownload as PowerPoint slideResearch highlights
► Norfloxacin and ciprofloxacin derivatives were synthesized and characterized.
► Novel rhenium and technetium-99m tricarbonyl complexes were synthesized and characterized.
► The 99mTc complexes showed satisfactory in vitro uptake by Escherichia coli and Staphylococcus aureus.