Iron Complexes of Square Planar Tetradentate Polypyridyl-Type Ligands as Catalysts for Water Oxidation

The tetradentate ligand, 2-(pyrid-2′-yl)-8-(1″,10″-phenanthrolin-2″-yl)-quinoline (ppq) embodies a quaterpyridine backbone but with the quinoline C8 providing an additional sp² center separating the two bipyridine-like subunits. Thus, the four pyridine rings of ppq present a neutral, square planar host that is well suited to first-row transition metals. When reacted with FeCl₃, a μ-oxo-bridged dimer is formed having a water bound to an axial metal site. A similar metal-binding environment is presented by a bis-phenanthroline amine (dpa) which forms a 1:1 complex with FeCl₃. Both structures are verified by X-ray analysis. While the Fe^III(dpa) complex shows two reversible one-electron oxidation waves, the Fe^III(ppq) complex shows a clear two-electron oxidation associated with the process H₂O–Fe^IIIFe^III → H₂O–Fe^IVFe^IV → OFe^VFe^III. Subsequent disproportionation to an FeO species is suggested. When the Fe^III(ppq) complex is exposed to a large excess of the sacrificial electron-acceptor ceric ammonium nitrate at pH 1, copious amounts of oxygen are evolved immediately with a turnover frequency (TOF) = 7920 h^–1. Under the same conditions the mononuclear Fe^III(dpa) complex also evolves oxygen with TOF = 842 h⁻¹

Photochemical and Photobiological Activity of Ru(II) Homoleptic and Heteroleptic Complexes Containing Methylated Bipyridyl-type Ligands

Light-activated compounds are powerful tools and potential agents for medical applications, as biological effects can be controlled in space and time. Ruthenium polypyridyl complexes can induce cytotoxic effects through multiple mechanisms, including acting as photosensitizers for singlet oxygen (¹O₂) production, generating other reactive oxygen species (ROS), releasing biologically active ligands, and creating reactive intermediates that form covalent bonds to biological molecules. A structure–activity relationship (SAR) study was performed on a series of Ru­(II) complexes containing isomeric tetramethyl-substituted bipyridyl-type ligands. Three of the ligand systems studied contained strain-inducing methyl groups and created photolabile metal complexes, which can form covalent bonds to biomolecules upon light activation, while the fourth was unstrained and resulted in photostable complexes, which can generate ¹O₂. The compounds studied included both bis-heteroleptic complexes containing two bipyridine ligands and a third, substituted ligand and tris-homoleptic complexes containing only the substituted ligand. The photophysics, electrochemistry, photochemistry, and photobiology were assessed. Strained heteroleptic complexes were found to be more photoactive and cytotoxic then tris-homoleptic complexes, and bipyridine ligands were superior to bipyrimidine. However, the homoleptic complexes exhibited an enhanced ability to inhibit protein production in live cells. Specific methylation patterns were associated with improved activation with red light, and photolabile complexes were generally more potent cytotoxic agents than the photostable ¹O₂-generating compounds

Synthesis, in Vitro Evaluation and Cocrystal Structure of 4‑Oxo-[1]benzopyrano[4,3‑<i>c</i>]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate Dehydrogenase (<i>Cp</i>IMPDH) Inhibitors

Cryptosporidium inosine 5′-monophosphate dehydrogenase (<i>Cp</i>IMPDH) has emerged as a therapeutic target for treating Cryptosporidium parasites because it catalyzes a critical step in guanine nucleotide biosynthesis. A 4-oxo-[1]­benzopyrano­[4,3-<i>c</i>]­pyrazole derivative was identified as a moderately potent (IC₅₀ = 1.5 μM) inhibitor of <i>Cp</i>IMPDH. We report a SAR study for this compound series resulting in <b>8k</b> (IC₅₀ = 20 ± 4 nM). In addition, an X-ray crystal structure of <i>Cp</i>IMPDH·IMP·<b>8k</b> is also presented