Synthesis, photophysical characterization, and aerobic redox reactivity of electron-rich tellurorhodamine photocatalysts.

Tellurorhodamine dyes are a class of self-sensitizing chromophores that we have previously shown can photocatalytically oxidize a variety of organic and inorganic compounds with visible light, oxygen, and water. A new series of tellurorhodamine chromophores containing electron donating moieties were synthesized to explore how different electron donating groups affect photophysical properties and catalyst function. The synthesized complexes 1B, 1C, and 1D contain increasingly electron-donating substituents (Me, t-Butyl, OMe) on the xylene ring. 1A, containing an unsubstituted xylene, was synthesized for use as a control. UV-Vis spectroscopy was used to determine the photophysical properties of the dyes and for kinetic and thermodynamic studies. With visible light irradiation all dyes could be oxidized at room temperature to their corresponding telluroxides 2A, 2B, 2C, and 2D, as confirmed by mass spectroscopy. Comparative reduction studies using our previously established silane oxidation reaction showed that decreasing the electron density of the xylene moiety increased the rate of reduction, corresponding to a decrease in the experimental ΔG. 2D has the smallest energy barrier to silane oxidation, and a linear increase in rate with increasing substituent electron withdrawing nature was observed at low temperatures, and non-linearity at high temperatures.

Photocatalytic aerobic oxidation of benzylic alcohols and concomitant hydrogen peroxide production.

The photochemical oxidation of benzylic alcohols using N-hydroxyphthalimide (NHPI) catalyst, with Rose Bengal as a singlet oxygen photosensitizer, and the production of hydrogen peroxide (H2O2) under metal-free conditions is presented. Computational and experimental investigations support 1O2 as the oxidant that converts NHPI to the active radical intermediate phthalimide-N-oxyl (PINO). This is a green alternative to current methods of H2O2 production.

Orbital analysis of bonding in diarylhalonium salts and relevance to periodic trends in structure and reactivity.

Diarylhalonium compounds provide new opportunities as reagents and catalysts in the field of organic synthesis. The three center, four electron (3c-4e) bond is a center piece of their reactivity, but structural variation among the diarylhaloniums, and in comparison with other λ3-iodanes, indicates that the model needs refinement for broader applicability. We use a combination of Density Functional Theory (DFT), Natural Bond Orbital (NBO) Theory, and X-ray structure data to correlate bonding and structure for a λ3-iodane and a series of diarylchloronium, bromonium, and iodonium salts, and their isoelectronic diarylchalcogen counterparts. This analysis reveals that the s-orbital on the central halogen atom plays a greater role in the 3c-4e bond than previously considered. Finally, we show that our revised bonding model and associated structures account for both kinetic and thermodynamic reactivity for both acyclic phenyl(mesityl)halonium and cyclic dibenzohalolium salts.

Computational investigation into intramolecular hydrogen bonding controlling the isomer formation and pKa of octahedral nickel(II) proton reduction catalysts.

This work demonstrates the impact of intramolecular hydrogen bonding (H-bonding) on the calculated pKa of octahedral tris-(pyridinethiolato)nickel(II), [Ni(PyS)3]-, proton reduction catalysts. Density Functional Theory (DFT) calculations on a [Ni(PyS)3]- catalyst, and eleven derivatives, demonstrate geometric isomer formation in the protonation step of the catalytic cycle. Through Quantum Theory of Atoms in Molecules (QTAIM), we show that the pKa of each isomer is driven by intramolecular H-bonding of the proton on the pyridyl nitrogen to a sulfur on a neighboring ligand. This work demonstrates that ligand modification via the placement of electron-donating (ED) or electron-withdrawing (EW) groups may have unexpected effects on the catalyst's pKa due to intramolecular H-bonding and isomer formation. These factors need to be considered in computational work. This work suggests the possibility that modification of substituent placement on the ligands to manipulate H-bonding in homogeneous metal catalysts could be explored as a tool to simultaneously target both desired pKa and E° values in small molecule catalysts.

Functionalized resorcinarenes effectively disrupt the aggregation of αA66-80 crystallin peptide related to cataracts.

Cataracts, an eye lens clouding disease, are debilitating and while operable, remain without a cure. αA66-80 crystallin peptide abundant in cataracted eye lenses contributes to aggregation of αA-crystallin protein leading to cataracts. Inspired by the versatility of macrocycles and programmable guest selectivity through discrete functionalizations, we report on three water-soluble ionic resorcinarene receptors (A, B, and C) that disrupt the aggregation of αA66-80 crystallin peptide. A and B each possess four anionic sulfonate groups, while C includes four cationic ammonium groups with four flexible extended benzyl groups. Through multiple non-covalent attractions, these receptors successfully disrupt and reverse the aggregation of αA66-80 crystallin peptide, which was studied through spectroscopic, spectrometric, calorimetric, and imaging techniques. The αA66-80·receptor complexes were also explored using molecular dynamics simulation, and binding energies were calculated. Even though each of the three receptors can bind with the peptide, receptor C was characterized by the highest binding energy and affinity for three different domains of the peptide. In effect, the most efficient inhibitor was a cationic receptor C via extended aromatic interactions. These results highlight the potential of versatile and tunable functionalized resorcinarenes as potential therapeutics to reverse the aggregation of α-crystallin dominant in eye cataracts.

The multifunctional dopamine D2/D3 receptor agonists also possess inhibitory activity against the full-length tau441 protein aggregation.

Neurodegeneration leads to variety of diseases which are linked to aberrant protein or peptide aggregation, as a one possible mechanism. Hence, small drug molecules targeting aggregation are of interest. Tau protein aggregation is one of the biomarkers of neurodegenerative diseases and is a viable drug target. Toward multifunctional inhibitors, we aim to incorporate structural elements in a potential drug in order to preserve dopamine agonist activity, which elevates disease symptoms associated with motor skills, and promote inhibitory activity against aggregation of the full-length tau (2N4R, tau441) protein. In our design, we introduced various moieties (catechol, non-catechol, biphenyl, piperazine, and thiazole) to determine which functional group leads to the greatest aggregation inhibition of tau. In vitro, tau aggregation was induced by heparin and monitored by using fluorescence aggregation assay, transmission electron microscopy and 4,4'-Dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt (Bis-ANS) fluorescence spectroscopy. The catechol containing compounds, D-519 and D-520, prevented aggregation of tau. By contrast, non-catechol and thiazole containing compounds (D-264 and D-636) were poor inhibitors. The Bis-ANS studies revealed that the potent inhibitors bound solvent-exposed hydrophobic sites. Based on the density functional theory calculations on inhibitors tested, the compounds characterized with the high polarity and polarizability were more effective aggregation inhibitors. These findings could lead to the development of small multifunctional drug inhibitors for the treatment of tau-associated neurodegeneration.

Tellurorhodamine photocatalyzed aerobic oxidation of organo-silanes and phosphines by visible-light.

Tellurorhodamine, 9-mesityl-3,6-bis(dimethylamino)telluroxanthylium hexafluorophosphate (1), photocatalytically oxidizes aromatic and aliphatic silanes and triphenyl phosphine under mild aerobic conditions. Under irradiation with visible light, 1 can react with self-sensitized 1O2 to generate the active telluroxide oxidant (2). Silanes are oxidized to silanols and triphenyl phosphine is oxidized to triphenyl phoshine oxide either using 2, or 1 with aerobic irradiation. Kinetic experiments coupled with a computational study elucidate possible mechanisms of oxidation for both silane and phosphine substrates. First-order rates were observed in the oxidation of triphenyl phosphine and methyldiphenyl silane, indicating a substitution like mechanism for substrate binding to the oxidized tellurium(iv). Additionally, these reactions exhibited a rate-dependence on water. Oxidations were typically run in 50 : 50 water/methanol, however, the absence of water decreased the rates of silane oxidation to a greater degree than triphenyl phosphine oxidation. Parallel results were observed in solvent kinetic isotope experiments using D2O in the solvent mixture. The rates of oxidation were slowed to a greater degree in silane oxidation by 2 (kH/kD = 17.30) than for phosphine (kH/kD = 6.20). Various silanes and triphenyl phosphine were photocatalytically oxidized with 1 (5%) under irradiation with warm white LEDs using atmospheric oxygen as the terminal oxidant.

Selective Electrochemical versus Chemical Oxidation of Bulky Phenol.

The electrochemical oxidation of selected tert-butylated phenols 2,6-di-tert-butyl-4-methylphenol (1), 2,6-di-tert-butylphenol (2), 2,4,6-tri-tert-butylphenol (3), 2-tert-butylphenol (4), and 4-tert-butylphenol (5) was studied in an aprotic environment using cyclic voltammetry, square-wave voltammetry, and UV-vis spectroscopy. All compounds exhibited irreversible oxidation of the corresponding phenol or phenolate ion. Compound 2 was selectively electrochemically oxidized, while other phenol analogues underwent mostly chemical oxidation. The electrochemical oxidation of 2 produced a highly absorbing product, 3,5,3',5'-tetra-tert-butyl-4,4'-diphenoquinone, which was characterized by X-ray crystal diffraction. The electrochemical oxidation was monitored as a function of electrochemical parameters and concentration. Experimental and theoretical data indicated that the steric hindrance, phenoxyl radical stability, and hydrogen bonding influenced the outcome of the electrochemical oxidation. The absence of the substituent at the para position and the presence of the bulky substituents at ortho positions were structural and electrostatic requirements for the selective electrochemical oxidation.

Efficient Bimolecular Mechanism of Photochemical Hydrogen Production Using Halogenated Boron-Dipyrromethene (Bodipy) Dyes and a Bis(dimethylglyoxime) Cobalt(III) Complex.

A series of Boron-dipyrromethene (Bodipy) dyes were used as photosensitizers for photochemical hydrogen production in conjunction with [Co(III)(dmgH)2pyCl] (where dmgH = dimethylglyoximate, py = pyridine) as the catalyst and triethanolamine (TEOA) as the sacrificial electron donor. The Bodipy dyes are fully characterized by electrochemistry, X-ray crystallography, quantum chemistry calculations, femtosecond transient absorption, and time-resolved fluorescence, as well as in long-term hydrogen production assays. Consistent with other recent reports, only systems containing halogenated chromophores were active for hydrogen production, as the long-lived triplet state is necessary for efficient bimolecular electron transfer. Here, it is shown that the photostability of the system improves with Bodipy dyes containing a mesityl group versus a phenyl group, which is attributed to increased electron donating character of the mesityl substituent. Unlike previous reports, the optimal ratio of chromophore to catalyst is established and shown to be 20:1, at which point this bimolecular dye/catalyst system performs 3-4 times better than similar chemically linked systems. We also show that the hydrogen production drops dramatically with excess catalyst concentration. The maximum turnover number of ∼ 700 (with respect to chromophore) is obtained under the following conditions: 1.0 × 10(-4) M [Co(dmgH)2pyCl], 5.0 × 10(-6) M Bodipy dye with iodine and mesityl substituents, 1:1 v:v (10% aqueous TEOA):MeCN (adjusted to pH 7), and irradiation by light with λ > 410 nm for 30 h. This system, containing discrete chromophore and catalyst, is more active than similar linked Bodipy-Co(dmg)2 dyads recently published, which, in conjunction with our other measurements, suggests that the nominal dyads actually function bimolecularly.

A doubly deprotonated diimine dioximate metalloligand as a synthon for multimetallic complex assembly.

An electrocatalytically active cobalt diimine monoxime monoximate complex was deprotonated by 1-methylimidazole affording a doubly deprotonated complex that serves as a versatile precursor for synthesis of a variety of multimetallic complexes with Co-Zn, -Cd, -Mn and -Ru coordination. These complexes were studied using a combination of spectroscopic, analytical and electrochemical techniques, revealing the electronic and structural parameters unique to this new class of compounds. The ability of these complexes to catalyze proton reduction was also investigated. These complexes are homogeneous electrocatalysts for the hydrogen evolution reaction through reduction of [NEt3H][BPh4] in CH3CN, however decompose under extended electrolysis conditions.

DFT analysis into the intermediates of nickel pyridinethiolate catalysed proton reduction.

Nickel pyridine 2-thiolate (Ni(PyS)3(-)) has shown good stability and activity as a H2 generation catalyst for use in solar energy storage. The experimentally proposed catalytic pathway is explored using DFT calculations. Free energy changes along the reaction coordinate, spin states, localization of charge and geometry of the intermediates were explored. Calculations were performed using Gaussian 09 with a B3P86/6-31+G(d) basis set and a CPCM water solvation model. Of particular interest were our findings that the first reduction occurs at the nickel rather than through non-innocent ligands and that water coordination is not favourable although protonation of the pyridyl nitrogen causes dechelation. Sequential and concerted proton coupled electron transfer were considered in the formation of the hydride.

Evidence for the rapid conversion of primary photoexcitations to triplet states in seleno- and telluro- analogues of poly(3-hexylthiophene).

Broadband pump-probe spectroscopy is used to examine the ultrafast photophysics of the π-conjugated polymers poly(3-hexylselenophene) (P3HS) and poly(3-hexyltellurophene) (P3HTe) in solution. An excited-state absorption feature that we attribute to a transition in the triplet manifold appears on the picosecond time scale. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations support this assignment. The formation of triplets is consistent with significant fluorescence quenching observed in solutions of the neat polymers. Triplet formation occurs in ~26 and ~1.8 ps (upper limit) for P3HS and P3HTe, respectively. The successive decrease in fluorescence quantum efficiency and triplet formation time are consistent with intersystem crossing facilitated by the heavier selenium and tellurium atoms. These results strongly suggest that primary photoexcitations are rapidly converted into triplet states in P3HS and P3HTe.

Photocatalytic hydrogen production from a noble metal free system based on a water soluble porphyrin derivative and a cobaloxime catalyst.

A combination of noble-metal free components, a water soluble porphyrin photosensitizer zinc meso-tetrakis(1-methylpyridinium-4-yl)porphyrin chloride [ZnTMPyP(4+)]Cl4 (1) with cobaloxime complex [Co(III)(dmgH)2(py)Cl] (2) as a catalyst, creates an efficient system for photochemical hydrogen production acting under visible light with 280 TONs. This is the first example of a water soluble porphyrin acting as a photosensitizer for cobaloxime catalysed H2 production.

Thermal and photoreductive elimination from the tellurium center of π-conjugated tellurophenes.

This study introduces small molecule tellurophenes that can undergo photoreductive elimination. A tellurophene compound with strong light absorption properties and extended π-conjugation, 2,5-bis[5-(N,N'-dihexylisoindigo)]tellurophene (1), has been synthesized. Halogen oxidative addition to the tellurium center from various halogen sources gives the dibromo- (1Br2) and dichloro- (1Cl2) adducts, leading to a red-shift in the optical absorption properties. In the presence of excess opposing halogen, 1Br2 and 1Cl2 can interconvert, with equilibrium favoring the dichlorotellurophene adduct. Reductive elimination reactions were studied using optical absorption spectroscopy, NMR spectroscopy, thermogravimetric analysis, and matrix-assisted laser desorption/ionization (MALDI) analysis. Thermal reductive elimination from 1Br2 and 1Cl2 occurs in the solid-state to restore 1. Photoreductive elimination occurs under irradiation with green (505 nm) light in solution in the presence of a halogen trap with some decomposition. This is the first example of photoreductive elimination from a mononuclear tellurophene complex.

Reversible oxidation of a water-soluble tellurophene.

Oxidation of a novel water-soluble tellurophene [2,5-tellurophene-bisphenoxy(octaethylene glycol monomethyl ether)] by peroxide is electrochemically reversible. This tellurophene can also be oxidized by self-photosensitized singlet oxygen in an aqueous solution. The oxidized tellurophenes are studied by optical absorption spectroscopy, (1)H NMR, and electrochemistry.

Robust visible light photoswitching with ortho-thiol substituted azobenzenes.

Introduction of S-ethyl groups in all four ortho positions of azobenzene prevents reduction of the azo group by intracellular glutathione, while enhancing the absorptivity to ~10,000 M(-1) cm(-1) in the blue and green regions of the visible spectrum. cis-to-trans isomerization occurs thermally on the minutes timescale. Further, this substitution pattern permits switching with red light, a color that is more penetrating through biological tissues than other parts of the visible spectrum.

Designing and refining Ni(II)diimine catalysts toward the controlled synthesis of electron-deficient conjugated polymers.

Electron-deficient π-conjugated polymers are important for organic electronics, yet the ability to polymerize electron-deficient monomers in a controlled manner is challenging. Here we show that Ni(II)diimine catalysts are well suited for the controlled polymerization of electron-deficient heterocycles. The relative stability of the calculated catalyst-monomer (or catalyst-chain end) complex directly influences the polymerization. When the complex is predicted to be most stable (139.2 kJ/mol), these catalysts display rapid reaction kinetics, leading to relatively low polydispersities (∼1.5), chain lengths that are controlled by monomer:catalyst ratio, controlled monomer consumption up to 60% conversion, linear chain length growth up to 40% conversion, and 'living' chain ends that can be readily extended by adding more monomer. These are desirable features that highlight the importance of catalyst design for the synthesis of new conjugated polymers.

Photoswitching azo compounds in vivo with red light.

The photoisomerization of azobenzenes provides a general means for the photocontrol of molecular structure and function. For applications in vivo, however, the wavelength of irradiation required for trans-to-cis isomerization of azobenzenes is critical since UV and most visible wavelengths are strongly scattered by cells and tissues. We report here that azobenzene compounds in which all four positions ortho to the azo group are substituted with bulky electron-rich substituents can be effectively isomerized with red light (630-660 nm), a wavelength range that is orders of magnitude more penetrating through tissue than other parts of the visible spectrum. When the ortho substituent is chloro, the compounds also exhibit stability to reduction by glutathione, enabling their use in intracellular environments in vivo.

Poly(3-alkyltellurophene)s are solution-processable polyheterocycles.

The synthesis and characterization of a series of poly(3-alkyltellurophene)s are described. Polymers are prepared by both electrochemical and Kumada catalyst transfer polymerization methods. These polymers have reasonably high molecular weights (M(n) = 5.4-11.3 kDa) and can be processed in a manner analogous to that of their lighter atom analogues. All examples exhibit red-shifted optical absorption, as well as solid-state organization, as evidenced by absorption spectroscopy and atomic force microscopy. Overall, the synthesis and characterization of these materials open up a wide range of future studies involving tellurium-based polyheterocycles.

Ru-Pt and Ru-Pd heterobimetallic complexes based on a new ligand with two distinct chelate sites.

A new ligand p-[N-2-(2'-pyridyl)benzimidazolyl]-[N-2-(2'-pyridyl)indolyl]-benzene (L1) has been synthesized and fully characterized. L1 has two distinct chelating sites: one N,N-chelate site and one N,C-chelate site. This ligand has been found to be very effective in selective binding to two different metal ions. Two new heterobimetallic complexes Ru-Pt and Ru-Pd using L1 as the bridging ligand have been successfully synthesized and fully characterized. To understand the mutual influence of the two metal centers on electronic and photophysical properties, the corresponding monometallic Ru(II), Pt(II) and Pd(II) compounds have also been synthesized and investigated. All Ru(II)-containing complexes have been found to be luminescent. Electronic communication between the two different metal centers in the heterobimetallic compounds was found to be weak. The Pt(II) moiety appears to enhance the phosphorescent efficiency of the Ru(II) unit while the Pd(II) analogue has little influence.