Effect of Rhenium(i) Complexation on Aza-Michael Additions to 5-Amino-1,10-Phenanthroline with [18F]Ethenesulfonyl Fluoride towards PET Optical Tracer Development.

Conjugations with the recently developed [18F]ethenesulfonyl fluoride ([18F]ESF) were performed on 5-amino-1,10-phenanthroline, in its free form and coordinated to a rhenium(i) tricarbonyl complex, as a means of radiosynthesizing dual-modal optical and positron emission tomography (PET) tracers. The Michael-donating ability of the aromatic amine was noticeably perturbed on coordination with the rhenium(i) centre, resulting in decreased radiochemical yields from 34 %, in the case of the free ligand, to 1 %. We attribute the decreased nucleophilicity of the amine to metal deactivation from the electron-withdrawing feature of the rhenium(i) tricarbonyl centre, based on spectroscopic and computational evidence, thus highlighting this effect as a crucial parameter in designing late-stage metal coordination methods employing related aza-Michael additions. Photophysical analyses were also performed on the ESF-conjugated rhenium(i) complex, exhibiting a longer decay lifetime from the triplet metal-to-ligand charge transfer excited state when compared with the non-conjugated analogue. The perturbation caused by rhenium(i) on the nucleophilicity of a Michael donor is reported in this study, with greater radiochemical yields attributed to conjugation of the free ligand with an [18F]ethenesulfonyl fluoride prosthetic group than with the metal complex. DFT analyses were performed towards elucidating the reaction mechanism, alongside photophysical analyses, which provide the basis for further development of rhenium(i)-based PET optical tracers. [ABSTRACT FROM AUTHOR]