Metalloporphyrin sulfido, selenido, and imido complexes: synthesis, characterization, and transfer reactions

Metalloporphyrins containing metal-oxygen multiple bonds have been the focus of numerous studies. In contrast, the chemistry of species containing multiple bonds to the heavier chalcogenides or the Group 15 elements is underdeveloped. In general, this has been the result of a lack of suitable synthetic precursors for the preparation of non-oxo containing derivatives;A new simple method for the preparation of early transition metal porphyrin halide complexes, starting from a porphyrin dianion and a metal halide species, provides a high yield route to metalloporphyrin halides of vanadium, molybdenum, titanium, and tungsten. Utilizing the molybdenum halide complex, (TTP)MoCl[subscript]2, we have found a number of synthetic routes for the preparation of the first terminal sulfido and selenido molybdenum porphyrins, (TTP)Mo=X (X = S, Se). The molybdenum chalcogenides may also be generated by treatment of (TTP)Mo(PhC≡CPh) with (TTP)Sn=X, formally an intermetal two-electron redox process mediated by sulfur or selenium atom transfer. In an analogous manner, treatment of (TPP)Sn=X (X = S, Se) with (TTP)Sn(II) results in the reversible exchange of a sulfur or selenium atom. For this Sn(IV)/Sn(II) exchange, we have found that the rate of selenium atom transfer is over 200 times faster than that of sulfur atom transfer;Employing early transition metal porphyrin halide complexes as precursors, we have also been able to prepare novel imido complexes of titanium and molybdenum porphyrins. In a reaction analogous to atom transfer, treatment of (TTP)Mo=NPh with (TTP)Ti(PhC≡CPh) results in complete imido group transfer to give (TTP)Mo(PhC≡CPh) and (TTP)Ti=NPh. This dissertation focuses on the synthesis, characterization, and transfer reactions of these sulfido, selenido, and imido metalloporphyrins

3-Hydroxyflavones and 3-Hydroxy-4-oxoquinolines as Carbon Monoxide-Releasing Molecules

Carbon monoxide-releasing molecules (CORMs) that enable the delivery of controlled amounts of CO are of strong current interest for applications in biological systems. In this review, we examine the various conditions under which CO is released from 3-hydroxyflavones and 3-hydroxy-4-oxoquinolines to advance the understanding of how these molecules, or derivatives thereof, may be developed as CORMs. Enzymatic pathways from quercetin dioxygenases and 3-hydroxy-4-oxoquinoline dioxygenases leading to CO release are examined, along with model systems for these enzymes. Base-catalyzed and non-redox-metal promoted CO release, as well as UV and visible light-driven CO release from 3-hydroxyflavones and 3-hydroxy-4-oxoquinolines, are summarized. The visible light-induced CO release reactivity of recently developed extended 3-hydroxyflavones and a 3-hydroxybenzo[g]quinolone, and their uses as intracellular CORMs, are discussed. Overall, this review provides insight into the chemical factors that affect the thermal and photochemical dioxygenase-type CO release reactions of these heterocyclic compounds

Properties of Flavonol-based PhotoCORM in Aqueous Buffered Solutions: Influence of Metal Ions, Surfactants and Proteins on Visible Light-induced CO Release

The properties of the extended flavonol 3-hydroxy-2-phenyl-benzo[g]chromen-4-one (2a) in DMSO : aqueous buffer solutions at pH = 7.4, including in the presence of metal ions, surfactants and serum albumin proteins, have been examined. Absorption and emission spectral studies of 2a in 1 : 1 DMSO : PBS buffer (pH = 7.4) indicate that a mixture of neutral and anionic forms of the flavonol are present. Notably, in 1 : 1 DMSO : TRIS buffer (pH = 7.4) only the neutral form of the flavonol is present. These results indicate that the nature of the buffer influences the acid/base equilibrium properties of 2a. Introduction of a Zn(II) complex of 2a− to a 1 : 1 DMSO : aqueous buffer (TRIS or PBS, pH = 7.4) solution produces absorption and emission spectral features consistent with the presence of a mixture of neutral 2a along with Zn(II)-coordinated or free 2a−. The nature of the anionic species present depends on the buffer composition. PBS buffered solutions (pH = 7.4) containing the surfactants CTAB or SDS enable 2a to be solubilized at a much lower percentage of DMSO (3.3–4.0%). Solutions containing the cationic surfactant CTAB include a mixture of 2a and 2a− whereas only the neutral flavonol is present in SDS-containing buffered solution. Compound 2a is also solubilized in TRIS buffer solutions at low cocentrations of DMSO (3.3%, pH = 7.4) in the presence of serum albumin proteins. Stern–Volmer analysis of the quenching of the inherent protein fluorescence indicates static binding of 2a to the proteins. The binding constant for this interaction is lower than that found for naturally-occurring flavonols (quercetin or morin) or 3-hydroxyflavone. Compound 2a binds to Site I of bovine and human serum albumin proteins as indicated by competition studies with warfarin and ibuprofen, as well as by docking investigations. The quantum yield for CO release from 2a (λirr = 419 nm) under aqueous conditions ranges from 0.0006(3) when the compound is bound to bovine serum albumin to 0.017(1) when present as a zinc complex in a 1 : 1 DMSO : H2O solution. Overall, the results of these studies demonstrate that 2a is a predictable visible light-induced CO release compound under a variety of aqueous conditions, including in the presence of proteins

A bipyridine-ligated zinc(II) complex with bridging flavonolate ligation: synthesis, characterization, and visible-light-induced CO release reactivity

Metal-flavonolate compounds are of significant current interest as synthetic models for quercetinase enzymes and as bioactive compounds of importance to human health. Zinc-3-hydroxyflavonolate compounds, including those of quercetin, kampferol, and morin, generally exhibit bidentate coordination to a single ZnII center. The bipyridine-ligated zinc-flavonolate compound reported herein, namely bis(μ-4-oxo-2-phenyl-4H-chromen-3-olato)-κ3O3:O3,O4;κ3O3,O4:O3-bis[(2,2′-bipyridine-κ2N,N′)zinc(II)] bis(perchlorate), {[Zn2(C15H9O3)2(C10H8N2)2](ClO4)2}n, (1), provides an unusual example of bridging 3-hydroxyflavonolate ligation in a dinuclear metal complex. The symmetry-related ZnII centers of (1) exhibit a distorted octahedral geometry, with weak coordination of a perchlorate anion trans to the bridging deprotonated O atom of the flavonolate ligand. Variable-concentration conductivity measurements provide evidence that, when (1) is dissolved in CH3CN, the complex dissociates into monomers. 1H NMR resonances for (1) dissolved in d6-DMSO were assigned via HMQC to the H atoms of the flavonolate and bipyridine ligands. In CH3CN, (1) undergoes quantitative visible-light-induced CO release with a quantum yield [0.004 (1)] similar to that exhibited by other mononuclear zinc-3-hydroxyflavonolate complexes. Mass spectroscopic identification of the [(bpy)2Zn(O-benzoylsalicylate)]+ ion provides evidence of CO release from the flavonol and of ligand exchange at the ZnII center.A bipyridine-ligated zinc-flavonolate complex exhibiting bridging flavonolate coordination has been characterized by single-crystal X-ray crystallography. In acetonitrile, this compound dissociates into monomers and undergoes visible-light-induced CO release. © International Union of Crystallography, 2017

CO Sense and Release Flavonols: Progress toward the Development of an Analyte Replacement PhotoCORM for Use in Living Cells

Carbon monoxide (CO) is a signaling molecule in humans. Prior research suggests that therapeutic levels of CO can have beneficial effects in treating a variety of physiological and pathological conditions. To facilitate understanding of the role of CO in biology, molecules that enable fluorescence detection of CO in living systems have emerged as an important class of chemical tools. A key unmet challenge in this field is the development of fluorescent analyte replacement probes that replenish the CO that is consumed during detection. Herein, we report the first examples of CO sense and release molecules that involve combining a common CO-sensing motif with a light-triggered CO-releasing flavonol scaffold. A notable advantage of the flavonol-based CO sense and release motif is that it is trackable via fluorescence in both its pre- and postsensing (pre-CO release) forms. In vitro studies revealed that the PdCl2 and Ru(II)-containing CORM-2 used in the CO sensing step can result in metal coordination to the flavonol, which minimizes the subsequent CO release reactivity. However, CO detection followed by CO release is demonstrated in living cells, indicating that a cellular environment mitigates the flavonol/metal interactions

Alkoxido, Amido, and Imido Derivatives of Titanium(IV) Tetratolylporphyrin

Treatment of (TTP)TiCl2 (1) [TTP = meso-5,10,15,20-tetra-p-tolylporphyrinato dianion] with excess NaOR (R = Ph, Me, t-Bu) affords the bis(alkoxide) derivatives (TTP)Ti(OR)2 [R = Ph (2), Me (3), t-Bu (4)] in moderate yield. The corresponding amido derivative (TTP)Ti(NPh2)2(5) is prepared in an analogous fashion employing LiNPh2. The disubstituted complexes 2, 3, and 5 react cleanly with (TTP)TiCl2 to afford the ligand exchange products (TTP)Ti(OR)Cl [R = Ph (6), Me (7)] and (TTP)Ti(NPh2)Cl (8), respectively. The monosubstituted complexes 6−8are also obtained by treatment of 1 with 1 equiv of the appropriate NaOR or LiNPh2 reagent. Treatment of 5 with excess phenol produces the bis(phenoxide) derivative 2 and 2 equiv of HNPh2. The imido derivatives (TTP)TiNR [R = t-Bu (9), Ph (10), C6H4-p-Me (11)] are prepared by the treatment of 1 with excess LiNHR. The t-Bu derivative (9) is also obtained by reaction of 1 with excess H2N-t-Bu at elevated temperatures. The phenyl imido complex (10) may be produced by the reaction of 0.5 equiv of PhNNPh with (TTP)Ti(η2-EtC⋮CEt) in refluxing toluene. Finally, (TTP)TiNTMS (12) is obtained by oxidation of (TTP)Ti(η2-EtC⋮CEt) with N3TMS

Oxygen Atom Transfer Reactions of Chromium Porphyrins: An Electronic Rationale for Oxo Transfer versus μ-Oxo Product Formation

Treatment of (meso-tetra-p-tolylporphyrinato)chromium(IV) oxide, {TTP)Cr=O, with (octaethylporphyrinato)chromium( III) chloride, (OEP)Cr-Cl, in benzene results in the reversible exchange of axial ligands to form (TTP)Cr-Cl and (OEP)Cr=O. The net result is a formal one-electron redox process. This occurs with a second-order rate constant of 0.14 :1:: 0.01 M-1 s-1 to form an equilibrium mixture with K = 2.7 :1:: 0.1 at 30 °C (ill/* = 15.4 :1:: 0.7 kcaljmol, M* = -12 :1:: 2 cal/ (mol·K), ill/0 = -2.0 :1:: 0.4 kcaljmol, and M 0 = -4.6 :1:: 1.2 cal/ (mol·K)). Use of pivalate in place of chloride on the Cr(III) complex causes no significant change in the rate of this one-electron redox process. The sterically protected Baldwin\u27s C2-capped {porphyrinato)chromium(III) complex, (CAP)Cr-Cl, also undergoes oxygen atom transfer with (OEP)Cr=O at a similar rate. In addition, excess chloride inhibits the rate of oxygen transfer with chlorochromium(III) complexes. These results support an inner-sphere mechanism involving a ~-oxo intermediate which is formed after an initial ligand (chloride or pivalate) dissociation from the chromium(III) reductant