Cu(II/I)-Pyridinophane Complexes: O2 Reactivity and 64Cu PET Imaging Studies.

The redox versatility of copper between the Cu(I) and Cu(II) oxidation states is central to its function in a variety of biological processes, including electron transfer, oxygen transport, and redox catalysis by metalloenzymes. Motivated by these biological paradigms, we report the design and development of a new series of chelators based on the 2-aza[3,2](2,6)pyridinophane (RN3) ligands (RN3, R = H, Me, 2-methylpyridyl, and 2-methylpicolinate). These ligands are designed to replicate key features of metalloenzyme active sites and to modulate the copper coordination environment. The new RN3 ligands have been fully characterized by NMR spectroscopy, high-resolution mass spectrometry, and UV-vis spectrophotometric titrations. The Cu(I) and Cu(II) complexes supported by these ligands were synthesized and characterized structurally and spectroscopically to investigate the effects of ligand denticity, variation in donor atoms, and chelate ring size on coordination geometry, bond parameters, and redox behavior. Special attention is given to the reactivity of Cu(I) complexes toward O2, offering insights into pathways of O2 activation and reduction. The RN3 ligands also demonstrate promising stability and binding affinity for both Cu(II) and Cu(I) ions, underscoring their potential for 64Cu-based positron emission tomography (PET) imaging applications.