Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments. This has led to the development of light-induced CO-releasing molecules (photoCORMs). A goal in this field of research is the development of molecules that exhibit a combination of controlled CO release, favorable biological properties (e.g., low toxicity and trackability in cells), and structural tunability to affect CO release. Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation photoCORM. We show that 3-hydroxyflavone-based compounds are easily synthesized and modified to impart changes in absorption features and quantum yield for CO release, exhibit low toxicity, are trackable in cells, and can exhibit both O₂-dependent and -independent CO release reactivity.

A mononuclear Ni^II complex bearing the monoanion of 1-acetoxy-3-phenylpropane-2,3-dione (4) as a ligand has been prepared {[(6-Ph₂TPA)Ni{PhC(O)C(O)CHOC(O)CH₃)]ClO₄, 5; 6-Ph₂TPA = N,N-bis[(6-phenyl-2-pyridyl)methyl]-N-(2-pyridylmethyl)amine}. This complex was characterized by ¹H NMR, UV/Vis and IR spectroscopy, mass spectrometry, and elemental analysis. Exposure of solutions of 5 to O₂ did not result in any reaction over the course of hours. Deprotection of 5 by the addition of NaOCH₃ in methanol generated a Ni^II species (6) that contains a coordinated dianionic C(1)-H acireductone. Exposure of 6 to O₂ led to regioselective oxidative cleavage reactivity akin to that found for the Ni^II-containing acireductone dioxygenase enzyme. The strategy outlined herein is the first synthetic approach that enables examination of the oxidative reactivity of a synthetic Ni^II species containing a dianionic C(1)-H acireductone ligand.

Irradiation of 3-hydroxyflavonolato (3-Hfl) complexes of Mn^II, Co^II, Ni^II and Cu^II (1–4) at 300 nm under aerobic conditions results in dioxygenase-type reactivity and the formation of the corresponding divalent metal O-benzoylsalicylato (O-bs) complexes 8–11 and CO. The latter were characterized by using multiple methods, including elemental analysis, X-ray crystallography, NMR and/or EPR spectroscopy, mass spectrometry and IR spectroscopy. Compounds 1–4 serve as catalysts for the photoinduced reactivity of 3-hydroxyflavonol (3-HflH) to produce O-benzoylsalicylic acid as the major product. Spectroscopic studies (UV/Vis and ¹H NMR) show that each O-benzoylsalicylato complex 8–11 reacts with one equiv. of 3-hydroxyflavonol to regenerate 1–4 and enable turnover reactivity. Unlike what is observed for free 3-HflH, photoinduced reactions involving 1–4 and excess flavonol show only minor amounts of flavonol isomerization reactivity. These results indicate that the presence of a metal ion, whether under stoichiometric or catalytic conditions, facilitates the photoinduced degradation of 3-HflH to produce a carboxylic acid and CO as products.

Three mononuclear Ni^II complexes containing a 2-chloro-1,3-diketonate ligand and supported by the 6-Ph₂TPA chelate, as well as analogues that lack the 2-chloro substituent on the β-diketonate ligand, have been prepared and characterized. Upon irradiation at 350 nm under aerobic conditions, complexes containing the 2-chloro-substituted ligands undergo reactions to generate products resulting from oxidative cleavage, α-cleavage, and radical-derived reactions involving the 2-chloro-1,3-diketonate ligand. Mechanistic studies suggest that the oxidative cleavage reactivity, which leads to the production of carboxylic acids, is a result of the formation of superoxide, which occurs through reaction of reduced nickel complexes with O₂. The presence of the 2-chloro substituent was found to be a prerequisite for oxidative carbon–carbon bond-cleavage reactivity, as complexes lacking this functional group did not undergo these reactions following prolonged irradiation. The approach toward investigating the oxidative reactivity of metal β-diketonate species outlined herein has yielded results of relevance to the proposed mechanistic pathways of metalloenzyme-catalyzed β-diketonate oxidative cleavage reactions.