Exhaustive Hydrodefluorination or Deuterodefluorination of Trifluoromethylarenes via Metal-Free Photoredox Catalysis.

Perfluoroalkyl compounds are persistent environmental pollutants due to their chemical and thermal stability. Hydrodefluorination is one of the most promising strategies for the disposal of fluorine-containing compounds, which has attracted much attention from a broad spectrum of scientific communities. Herein, we disclose a metal-free, visible-light-promoted protocol for the exhaustive hydrodefluorination of a wide variety of trifluoromethylarenes with up to 95% yields. Moreover, methyl-d3 groups can be obtained via deuterium water with a D ratio of up to 94%.

Exactly controlled linear CO liberation: an A- and B-ring simultaneously extended flavonol-based red fluorescent photoCORM.

The first visible/sun-light-triggered A/B-ring-naphthalene/biphenyl simultaneously extended flavonol based red fluorescent photoCORM, Nbp-flaH (2-([1,1'-biphenyl]-4-yl)-3-hydroxy-4H-benzo[g]chromen-4-one), was developed. By simultaneously extending π-conjugation on the A- and B-ring of 3-hydroxyflavone (FlaH), the absorption peak and emission peak of Nbp-flaH were largely red-shifted by 75 and 100 nm, respectively, relative to those of FlaH, thus emitting strong and bright red fluorescence (610 nm, near the phototherapeutic window), with a large Stokes shift of 190 nm. Therefore, Nbp-flaH can be triggered by visible/sun-light, and its location in living HeLa cells and the process of CO delivery can be real-time imaged and tracked in situ. By irradiation with visible light under O2, Nbp-flaH can release CO rapidly (t1/2 = 3.40 min) with a high yield (over 90%), and the dose of CO liberated can be quantitatively regulated within a safe and therapeutic dose range by changing the irradiation intensity or time or photoCORM dose. Nbp-flaH and its reaction products exhibit negligible toxicity (more than 85% cell viability, 24 h) and good permeability in live HeLa cells. This is the first A- and B-ring-simultaneously extended (to naphthalene and biphenyl, respectively) flavonol developed as a red fluorescent photoCORM, which can be triggered by visible/sun-light and deliver accurately and quantitatively controlled linear CO in live HeLa cells. Our work would provide not only a reliable method to precisely control the CO release dose for clinical CO therapy, but also a convenient tool for studying the biological role of CO.

Indole-substituted flavonol-based cysteine fluorescence sensing and subsequent precisely controlled linear CO liberation.

The first water-soluble B-ring-indole-substituted flavonol-based cysteine (Cys) fluorescent probe, MICA (2-(1-methyl-1H-indol-3-yl)-4-oxo-4H-chromen-3-yl-acrylate), was developed, which simultaneously serves as a precursor of photoCORM. In PBS buffer (only 15% DMF), MICA can perform rapid (330 s), highly chemoselective (particularly for homocysteine and glutathione) and sensitive (limit of detection: 92 nM) sensing and visualization of exogenous and endogenous Cys in live HeLa cells and zebrafish over a wide linear concentration range (0-12 µM/2.4 equiv.). The fluorophore HMIC (3-hydroxy-2-(1-methyl-1H-indol-3-yl)-4H-chromen-4-one), actuated and quantitatively generated via the sensing reaction of the precursor MICA with Cys, was designed as a photoCORM. By modulating the light illumination intensity or illumination duration or photoCORM dosage, HMIC can provide precisely controlled quantitative and linear CO gas by visible light illumination in aerobic environments. For live HeLa cells, MICA and all reaction products showed low toxicity (over 85% cell viability versus 10 µM analyst) and efficient cellular uptake. In live HeLa cells and zebrafish, both exogenous and endogenous Cys can be visualized by MICA, and the location and CO liberation process of the generated HMIC can be tracked in real time through its fluorescence. Substitution of the B-ring of 3-hydroxy-flavone (3-FL) by indole results in a 52 nm absorption red-shift vs.3-FL. Our work is the first water-soluble B-ring-indole-substituted flavonol-based fluorescent probe that efficaciously detects and visualizes exogenous and endogenous Cys both in vitro and in vivo, simultaneously serving as a precursor of photoCORM, actuated by Cys and triggered by visible light, releasing linear CO in aerobic environments. This work not only provides promising applications for the detection and visualization of exogenous and endogenous Cys, and spatiotemporally controllable CO liberation in live systems, but will also facilitate the development of handy molecular tools for clinical diagnosis and CO gas therapy.

B-Ring-extended flavonol-based photoCORM: activated by cysteine-ratiometric fluorescence sensing and accurate control of linear CO release.

The first B-ring-extended (to biphenyl) flavonol-based Cys-ratiometric fluorescent probe B-bph-fla-acr (2-([1,1'-biphenyl]-4-yl)-4-oxo-4H-chromen-3-yl acrylate) is developed. B-bph-fla-acr can ratiometrically sense and non-ratiometrically image endogenous and exogenous cysteine (Cys) in living HeLa cells and zebrafish rapidly (45 s), selectively (vs. homocysteine and glutathione), sensitively (detection limit: 18.5 nM), and with a large Stokes shift (186 nm). Quantitatively released (from the reaction of B-bph-fla-acr with Cys) fluorophore B-bph-fla-OH (2-([1,1'-biphenyl]-4-yl)-3-hydroxy-4H-chromen-4-one) is designed as a photoCORM (photo-triggered CO releasing molecule). Under O2 and visible light irradiation, the amount of CO released by B-bph-fla-OH can be accurately controlled linearly by adjusting the light irradiation intensity, irradiation time, or photoCORM dose. This process is accompanied by fluorescence quenching; therefore, the location of the photoCORM and the CO release process can be monitored in real time. B-bph-fla-acr and all reaction products exhibit good membrane permeability and low toxicity for living HeLa cells. In living HeLa cells and zebrafish, B-bph-fla-acr can image endogenous and exogenous Cys, and the released B-bph-fla-OH can photo-release CO under O2 at room temperature. This study is the first to combine a B-ring-extended flavonol-based fluorescent probe (for the effective ratiometric sensing and non-ratiometric imaging of endogenous and exogenous Cys in vitro and in vivo) with a photoCORM (Cys-activated, visible light-triggered linear CO release under O2). Our study provides important insights into the biological roles of Cys and CO, as well as a reliable method for safely supplying accurately controlled amounts of CO to living systems, thereby facilitating the development of convenient clinical diagnostic molecular tools and therapeutic prodrugs.

A trichromatic MOF composite for multidimensional ratiometric luminescent sensing.

Low-cost, high-performance luminescent probes with wide application potential have been actively pursued. Conventional luminescent probes, which rely on single or dual emissions responsive to analyte molecules, demonstrate limited sensitivity and selectivity because the single emissions can be easily affected by many non-analyte factors, while the dual emissions can only offer single-ratiometric luminescent sensing. Here we report a white-light-emitting trichromatic MOF composite (W2) as the first multidimensional ratiometric luminescent probe. It is facilely synthesized by simultaneously incorporating red- and green-emitting iridium and ruthenium complex cations as encapsulated luminescent modules (ELMs) into a porous blue-emitting MOF via ion exchange. Specific volatile organic solvents (VOSs) can cause VOS-dependent changes to the MOF-to-ELM energy transfer efficiencies in W2, while nitroaromatic (NAC) vapors intriguingly and unprecedentedly quench the three emissions at different rates, both of which enable visible luminescent sensing. Each VOS can be correlated to a unique combination of the two MOF-to-ELM ratios of emission-peak heights, enabling a two-dimensional (2D) code recognition. Furthermore, the time-dependent evolution of the two ratios upon exposure to selective NAC vapors can be mapped out, achieving the first 3D code recognition. Both the synthetic and sensing strategies can be further implemented to develop low-cost and effective luminescent probes.

A Trichromatic and White-Light-Emitting MOF Composite for Multi-Dimensional and Multi-Response Ratiometric Luminescent Sensing.

Present here is a new dual ratiometric luminescent probe D which is a trichromatic and white-light-emitting metal-organic framework (MOF) composite facilely obtained by incorporating red/green-emitting complex modules into a blue-emitting MOF. Probe D exhibits remarkable capabilities of sensing different volatile organic solvents (VOSs) via 2D code recognition of the two VOS-dependent MOF ligand-to-module ratios of the emission-peak intensities. For specific VOSs, the resultant luminescent color changes from the starting white color are sharp enough to be visible to the naked eye. Remarkably, D can differentiate solution-phase nitroaromatics and metal ions by recording the evolution of the two ratios during titration processes, enabling an unusual 3D code recognition using the titrant amount as the third dimension for the first time. D also can be used to detect dinoseb, Fe3+ and Al3+ ions quantitatively by analysis of the ratios with detection limits as low as 0.050, 0.41, and 0.12 ppm, respectively. Clearly, such a self-referencing trichromatic probe can maximize the output information and significantly enhance the detection selectivity and sensitivity via multi-dimensional sensing, and has great potentials for practical applications.

Set of Fe(II)-3-Hydroxyflavonolate Enzyme-Substrate Model Complexes of Atypically Coordinated Mononuclear Non-Heme Fe(II)-Dependent Quercetin 2,4-Dioxygenase.

With the aim of revealing the catalytic role of atypically coordinated (3His-1Glu) active site mononuclear non-heme Fe(II)-dependent quercetin 2,4-dioxygenase (Fe-2,4-QD) and the electronic effects of the model ligands on the reactivity toward dioxygen, a set of p/m-R-substituted carboxylate-containing ligand-supported Fe(II)-3-hydroxyflavonolate complexes, [FeIILR(fla)] (LRH: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-p/m-R-benzoic acid; R: p-OMe (1), p-Me (2), m-Br (4), and m-NO2 (5); fla: 3-hydroxyflavonolate), were synthesized and characterized as structural and functional models for the ES (enzyme-substrate) complexes of Fe-2,4-QD. [FeIILR(fla)] show relatively high enzyme-type reactivity (dioxygenative ring opening of the coordinated substrate fla, single-turnover reaction) at low temperatures (30-65 °C). The reaction shows a linear Hammett plot (ρ = -1.21), and electron donating groups enhance the reaction rates. The notable difference on the reactivity can be rationalized from the electronic nature of the substituent in the ligands, which could tune the reactivity via tuning Lewis acidity of the Fe(II) ion, electron density, and the redox potential of fla. The properties and the reactivity show approximately linear correlations between λmax or E 1/2 of fla and the reaction rate constant k. This work sheds light not only on understanding of electronic effects of the ligands and the property-reactivity relationship but also on the role of the catalytic reaction by Fe-2,4-QD.

Catalytic dioxygenation of flavonol by M(II)-complexes (M = Mn, Fe, Co, Ni, Cu and Zn) - mimicking the M(II)-substituted quercetin 2,3-dioxygenase.

In order to get insights into the metal ion effects and the carboxylate effects on enzymatic activity, a series of the carboxylate ligand supported transition metal complexes [M(II)L(OAc)] (M = Mn (), Fe (), Co (), Ni (), Cu () and Zn (); LH = 2-{[bis-(pyridin-2-ylmethyl)amino]methyl}-4-methoxy benzoic acid) were synthesized and characterized as structural and functional models for the active sites of various M(II)-substituted resting quercetin 2,3-dioxygenases (2,3-QD). Their structures, spectroscopic features, redox properties, as well as the catalytic reactivity toward the substrate flavonol and O2 have been investigated in detail. The model complexes show higher enzymatic reactivities in the catalytic dioxygenation (oxidative ring opening) of the substrate flavonol at lower temperatures (55-100 °C), presumably caused by the carboxylate group in the supporting model ligand, which could lower the redox potential of the bound substrate flavonolate by electron donation. The catalytic reactivity of [M(II)L(OAc)] exhibits notable differences and it is in a metal ion dependent order of Co () > Ni () > Zn () > Fe () > Mn () > Cu (). The differences in the reactivities among them could be ascribed to the redox potential of the bound substrate flavonolate, which was drastically influenced by the metal ions via tuning the electron density of flavonolate, providing important insights into the metal ion effects and the carboxylate effects on the enzymatic activity of various M(II)-substituted 2,3-QD. Our model complexes [M(II)L(OAc)] are the first examples of a series of structural and functional models of various M(II)-substituted resting 2,3-QD.

Triflic acid mediated cascade cyclization of aryldiynes for the synthesis of indeno[1,2-c]chromenes: application to dye-sensitized solar cells.

A new triflic acid (TfOH)-mediated cascade cyclization of ortho-anisole-substituted aryldiynes is described for the construction of indeno[1,2-c]chromenes. The cascade cyclization proceeds through an unusual TfOH-induced alkyne-alkyne cyclization followed by nucleophilic attack of the methoxy group on the benzylidene cation, which is completely different to the cyclization of ortho-aniline- or ortho-thioanisole-substituted aryldiynes. A new class of organic dyes with the indeno[1,2-c]chromene framework as both donor and π-linker were synthesized. These compounds exhibit high photovoltaic performances in dye- sensitized solar cells (DSCs).

A series of Ni(II)-flavonolate complexes as structural and functional ES (enzyme-substrate) models of the Ni(II)-containing quercetin 2,3-dioxygenase.

Ni(II)-flavonolate complexes [Ni(II)L(R)(fla)] (L(R)H: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-p/m-R-benzoic acid, R: p-OMe (1), p-Me (2), m-Br (4) and m-NO2 (5), fla: flavonolate) were synthesized and characterized with relevance to structural and functional models for the ES (enzyme-substrate) adduct of the Ni(II)-containing quercetin 2,3-dioxygenase (2,3-QD). Their structures, spectroscopic features, redox properties and the reactivity toward molecular oxygen have been investigated. The complexes show a similar distorted octahedral structure and higher enzyme-type dioxygenation reactivity than other reported metal-flavonolate complexes in the oxidative O-heterocyclic ring-opening of the bound substrate flavonolate at lower temperature owing to the introduced carboxylate group in the supporting model ligands. The reaction rate shows first-order dependence on both of the complex and O2 and the second-order rate constant k fits a Hammett linear free energy relationship (ρ = -0.71) for the substituent group in the supporting model ligand L(R). The complexes exhibit substituent group dependent structures, properties and reactivity and there are some relationship among them, which could be ascribed to the electronic nature of the substituent group via the benzoate, Ni(II) ion and O(4)=C(27)-C(21)=C(22) "electron conduit". In a word, the stronger electron donating group could induce a smaller torsion angle, larger λ(max) and lower redox potential of the bound flavonolate, making a higher reactivity finally. This study is the first example of a series of structural and functional ES models of the Ni(II)-containing 2,3-QD, providing important insights into the structure-property-reactivity relationship, the electronic substituent effects and carboxylate effects on the enzymatic reactivity and the catalytic role of the Ni(II)-containing 2,3-QD.

Series of structural and functional models for the ES (enzyme-substrate) complex of the Co(II)-containing quercetin 2,3-dioxygenase.

A series of mononuclear Co(II)-flavonolate complexes [Co(II)L(R)(fla)] (L(R)H = 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-p/m-R-benzoic acid; R = p-OMe (1), p-Me (2), m-Br (4), and m-NO2 (5); fla = flavonolate) were designed and synthesized as structural and functional models for the ES (enzyme-substrate) complexes to mimic the active site of the Co(II)-containing quercetin 2,3-dioxygenase (Co-2,3-QD). The metal center Co(II) ion in each complex shows a similar distorted octahedral geometry. The model complexes display high enzyme-type dioxygenation reactivity (oxidative O-heterocyclic ring opening of the coordinated substrate flavonolate) at low temperature, presumably due to the attached carboxylate group in the ligands. The reactivity exhibits a substituent group dependent order of -OMe (1) > -Me (2) > -H (3)14b > -Br (4) > -NO2 (5), and the Hammett plot is linear (ρ = -0.78). This can be explained as the electronic nature of the substituent group in the ligands may influence the conformation and redox potential of the bound flavonolate and finally bring different reactivity. The structures, properties, and reactivity of the model complexes show some dependence on the substituent group in the supporting model ligands, and there is some relationship among them. This study is the first example of a series of structural and functional ES models of Co-2,3-QD, with focus on the effects of the electronic nature of substituted groups and the carboxylate group of the ligands to the dioxygenation reactivity, that will provide important insights into the structure-property-reactivity relationship and the catalytic role of Co-2,3-QD.

Flavonolate complexes of M(II) (M = Mn, Fe, Co, Ni, Cu, and Zn). Structural and functional models for the ES (enzyme-substrate) complex of quercetin 2,3-dioxygenase.

A series of flavonolate complexes [M(II)L(fla)] (M = Mn (1), Fe (2), Co (3), Ni (4), Cu (5), and Zn (6), LH: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}benzoic acid, fla: flavonolate) have been synthesized as structural and functional models for the ES (enzyme-substrate) complexes of the active site of various M(II)-containing quercetin 2,3-dioxygenase (2,3-QD) and their structures, spectroscopic features, and redox properties, as well as the reactivity toward molecular oxygen, have been investigated. The metal centers of [Fe(II)L(fla)]·H2O (2), [Co(II)L(fla)]·CH3OH (3), and [Ni(II)L(fla)] (4) exhibit a distorted octahedral geometry with two oxygen atoms of fla, one oxygen atom of the benzoate group of ligand L, and three nitrogen atoms of ligand L, in which oxygen atom of the carbonyl group of fla and one of the pyridine nitrogen atoms occupy the axial positions. The complexes [M(II)L(fla)] exhibit relatively high reactivity in the oxidative ring-opening of the bound flavonolate at lower temperature, presumably due to the existing carboxylate group in the supporting ligand. Thus, our complexes act as good functional ES models of various metal(II)-containing 2,3-QD. In addition, complexes [Fe(II)L(fla)]·H2O (2), [Co(II)L(fla)]·CH3OH (3), and [Ni(II)L(fla)] (4) are the first structurally characterized Fe(II)-, Co(II)-, and Ni(II)-flavonolate complexes, as an active site ES model of Fe(II)-, Co(II)-, and Ni(II)-containing 2,3-QD, respectively. The model complexes exhibit notably different reactivity in the order of Fe (2) > Cu (5) > Co (3) > Ni (4) > Zn (6) > Mn (1). The differences in the reactivity among them may be attributed to the redox potential of the coordinated flavonolate of the complexes, which are remarkably influenced by the Lewis acidity of the metal ion and its coordination environment. Our study is the first example of the metal ion effects on the enzyme-like dioxygenation reactivity, providing important insights into the metal ion effects on the enzymatic reactivity of various metal(II)-containing 2,3-QD.

Mechanistic insights into the reversible formation of iodosylarene-iron porphyrin complexes in the reactions of oxoiron(IV) porphyrin pi-cation radicals and iodoarenes: equilibrium, epoxidizing intermediate, and oxygen exchange.

We have shown previously that iodosylbenzene-iron(III) porphyrin intermediates (2) are generated in the reactions of oxoiron(IV) porphyrin pi-cation radicals (1) and iodobenzene (PhI), that 1 and 2 are at equilibrium in the presence of PhI, and that the epoxidation of olefins by 2 affords high yields of epoxide products. In the present work, we report detailed mechanistic studies on the nature of the equilibrium between 1 and 2 in the presence of iodoarenes (ArI), the determination of reactive species responsible for olefin epoxidation when two intermediates (i.e., 1 and 2) are present in a reaction solution, and the fast oxygen exchange between 1 and H(2)18O in the presence of ArI. In the first part, we have provided strong evidence that 1 and 2 are indeed at equilibrium and that the equilibrium is controlled by factors such as the electronic nature of iron porphyrins, the electron richness of ArI, and the concentration of ArI. Secondly, we have demonstrated that 1 is the sole active oxidant in olefin epoxidation when 1 and 2 are present concurrently in a reaction solution. Finally, we have shown that the presence of ArI in a reaction solution containing 1 and H(2)18O facilitates the oxygen exchange between the oxo group of 1 and H(2)18O and that the oxygen exchange is markedly influenced by factors such as ArI incubation time, the amounts of ArI and H(2)18O used, and the electronic nature of ArI. The latter results are rationalized by the formation of an undetectable amount of 2 from the reaction of 1 and ArI through equilibrium that leads to a fast oxygen exchange between 2 and H(2)18O.

Spectroscopic properties, catalytic activities and mechanism studies of [(TpPh)Co(X)(CH3OH)m] . nCH3OH: bicarbonate dehydration in the presence of inhibitors.

Two inhibitor-containing 'half-sandwich' cobalt(II) complexes [(TpPh)Co(X)(CH3OH)m] x nCH3OH ((TpPh) = hydrotris (3-phenylpyrazolyl)borate; 1: X- = N3-, m = 1, n = 2; 2: X- = NCS-, m = 0, n = 0) have been synthesized and used as the catalysts in the bicarbonate dehydration reaction. The structures of 1 and 2 were determined by X-ray diffraction analysis, which shows that N3- and NCS- coordinate to the Co(II) ions of 1 and 2, respectively, with the Co-N bond lengths of 1.992(6) A and 1.901(3) A. The coordination geometries of the Co(II) complexes in solution are five-coordinated trigonal bipyramid as revealed by the spectroscopic measurements. The dehydration kinetic measurements of HCO3- are performed by the stopped-flow techniques at pH < 7.9. The apparent dehydration rate constant k(obs) varies linearly with Co(II) complex and H+ concentrations, respectively, and the catalytic activity of 2 is lower than that of 1. The aqua Co(II) complex must be the reactive catalytic species in the catalyzed dehydration reaction and the rate-determining step is the substitution of the labile water molecule by HCO3-. The k(obs) values increase with increasing reaction temperature, and the large negative entropy of activation also indicates the associative activation mode. The inhibition ability of NCS- is stronger than that of N3-, which can be rationalized by the decreases in the Co-N(N3-/NCS-) bond lengths and effective atomic charges of the Co(II) ions based on the X-ray crystallographic data and theoretical calculations in this work.

Factors affecting the catalytic epoxidation of olefins by iron porphyrin complexes and H2O2 in protic solvents.

The catalytic epoxidation of cyclohexene by iron(III) porphyrin complexes and H2O2 has been investigated in alcohol solvents to understand factors affecting the catalyst activity in protic solvents. The yields of cyclohexene oxide and the Fe(III/II) reduction potentials of iron porphyrin complexes were significantly affected by the protic solvents, and there was a close correlation between the product yields and the reduction potentials of the iron porphyrin catalysts. The role of alcohol solvents was proposed to control the electronic nature of iron porphyrin complexes that determines the catalyst activity in the epoxidation of olefins by H2O2. We have also demonstrated that an electron-deficient iron porphyrin complex can catalyze the epoxidation of olefins by H2O2 under conditions of limiting substrate with high conversion efficiency in a solvent mixture of CH3OH and CH2Cl2.

Kinetic study of the effects of inhibitors on the catalyzed dehydration of HCO3- by copper(II) complexes [TpPh]CuX (X- = OH-, N3-, NCS-).

A series of half-sandwich copper(II) complexes [TpPh]CuX ([TpPh] = hydrotris(3-phenyl-pyrazolyl)borate; X- = OH- (1), N3- (2), NCS- (3)) have been synthesized as models for carbonic anhydrase. The structure of 3 was determined by X-ray diffraction analysis. Crystals of 3 (C37H30BCuN9S) are triclinic, space group P1 with a = 11.997(3) A, b = 12.116(3) A, c = 13.384(4) A, alpha = 81.088(5) degrees, beta = 79.289(6) degrees, gamma = 68.668(5) degrees, V = 1772.4(8) A3, and Z = 2. The dehydration kinetic measurements of HCO3- are performed by the stopped-flow techniques at pH < 7.9. The apparent dehydration rate constant kdobs varies linearly with total Cu(II) concentration, and the catalytic activity of the model complexes decreases in the order 1 > 2 > 3. The catalytic activity decreases with increasing pH indicating that the aqua model complex must be the reactive catalytic species in the catalyzed dehydration reaction and the rate-determining step is the substitution of the labile water molecule by HCO3-. The kdobs values increase with increasing reaction temperature, and the apparent activation energies of the model complexes with inhibitors are remarkably higher than that of the complex with no inhibitors, this being the origin of inhibition. The large negative entropy of activation also indicates an associative mode of activation in the rate-determining step. The inhibition ability of the inhibitor NCS- is stronger than that of the inhibitor N3-, which can be rationalized by the decrease in effective atomic charges of the Cu(II) ions as revealed by the theoretical calculations.