Synthesis, characterization, and applications of pyridine- and pyridol-based azamacrocyclic transition metal complexes

Abstract

The Green group has designed and synthesized a series of pyridine- and pyridol-based azamacrocycles, L1-L9. Azamacrocycles are a unique class of ligands that form exceptionally stable complexes with transition metals, due to the macrocyclic effect.(ref. 1-2) The corresponding metal complexes have exceptional structural, kinetic, thermodynamic, spectral, and electrochemical properties that have long been studied by researchers.(ref. 2) Additionally, these macrocyclic metal complexes have a broad range of applications such as use as biomimetic models, catalysts, or therapeutic/diagnostic agents. This work presents the synthesis, characterization, and applications of L1-L5 (gen. 1 and 2) and corresponding transition metal complexes. Ligands L1-L3 were complexed to manganese and cobalt; these complexes were studied using traditional inorganic spectroscopic techniques.^Ligand-cobalt complexes exhibit a unique solvent-dependent equilibrium behavior similar to the classic cobalt(II) chloride equilibrium, which is often used to illustrate Le Châteliers Principle.(ref. 8) The ligand-manganese complexes can be modulated between mononuclear or dinuclear depending on the pH of solution during synthesis. Mononuclear Mn(III) complexes offer the potential to be utilized as oxidation catalysts. Additionally, resulting dinuclear di-µ-oxo bridged complexes offer connectivity to historically significant biomimetic model complexes. Within the literature, Mn(III,IV) di--µ-oxo bridged dimers have traditionally been used to model the active site of the oxygen evolving complex (OEC) with photosystem II (PSII).(ref. 9) L4, was designed to enhance the radical scavenging abilities exhibited by L2, by doubling the number of pyridol-rings present within the ligand.^These pyridol-based macrocycles offer the potential to be used as therapeutics for the treatment of neurodegenerative disorders by combating reactive oxygen species and sequestering misregulated metal ions. After synthesizing L4, it was complexed to several biologically relevant metal ions, Cu(II) and Zn(II). Additionally, radical scavenging assays were performed, as well as cell studies to determine the therapeutic window of L4. Finally, L5 was originally designed to be a rigid 15-membered pentaazamacrocycle for use as a Mn(II)-based contrast agent. Due to the presence of piperazine-rings, a 30-membered decaazamacrocyclic dimer was isolated instead. Although this ligand forms weak complexes with transition metal ions, it will be explored as a potential anion receptor in the future, due to its six protonation events.