Ligand redox controlled amine dehydrogenation and imine hemilability in singlet diradical azo-aromatic Ni(II) complexes: characterization of the electron transfer series of azo-imine complexes of Ni(II).

Herein, using azo-amine (H2L) and azo-imine (L1-3) ligands, singlet diradical Ni(II) complexes [1] and [2] were synthesized from Ni(0)(COD)2 in THF. In separate reactions, homoleptic NiII complexes, [3a]2+-[3c]2+, were synthesized from [NiII(H2O)6](ClO4)2 and L1-3, respectively. All these complexes were characterized thoroughly. The X-ray structures of [1] and [2] showed that the amine side arm in [1] and the imine side arm in [2] are de-coordinated. The dN-N lengths in these two complexes were found to be ∼1.32 Å, which corresponds to the one-electron reduced azo-bond length. These complexes, [1] and [2], showed 1H NMR signals characteristic of diamagnetic compounds. These studies, along with DFT calculations, indicated that the unpaired spins on ligands coupled antiferromagnetically with the two unpaired spins on NiII to result in s = 0 ground states. Complex [1] showed ligand-based redox-induced dehydrogenation of the distal amine side arm to result in L1. Complexes [3a]2+-[3c]2+ have dN-N lengths of ∼1.27 Å and dC-N lengths of ∼1.28 Å. In cyclic voltammetry, complex [3a]2+ showed four well-resolved reversible reductive waves at 0.5 V to -1.6 V in dichloromethane. The first two waves became irreversible when they were measured in acetonitrile solution. The electron transfer series of [3a]2+ was further characterized by spectro-electrochemistry, EPR, and DFT calculations. These showed that all the reductions were associated with the ligand. It was further probed by redox events in complexes [3b]2+ and [3c]2+. While the electron donor -OMe group on the phenyl ring of the azo moiety in [3b]2+ showed a prominent cathodic shift of the potentials, the -F substitution on the phenyl group on the imine side arm of [3c]2+ has almost no effect. It has to be noted here that the oxidation of [2] by two electrons returns it back to complex [3a]2+. Reduction of [3a]2+ by two electrons also resulted in complex [2], indicating reversible ligand redox-induced hemilability of the imine moiety between [3a]2+ and [2]. Moreover, characterization of the electron transfer series of [3a]2+ and [2] has shown superior redox non-innocent behaviour and coordination ability of the azo-pyridine moiety in nickel(II) complexes over the imino-pyridine moiety of the ligand.

A Phosphine-Oxide Cobalt(II) Complex and Its Catalytic Activity Studies toward Alcohol Dehydrogenation Triggered Direct Synthesis of Imines and Quinolines.

Herein, a new pincer-like amino phosphine donor ligand, H2L1, and its phosphine-oxide analog, H2L2, were synthesized. Subsequently, cobalt(II) complexes 1 and 2 were synthesized by the reaction of anhydrous Co(II)Cl2 with ligands H2L1 and H2L2, respectively. The ligands and complexes were fully characterized by various physicochemical and spectroscopic characterization techniques. Finally, the identity of the complexes 1 and 2 was confirmed by single crystal X-ray structure determination. The phosphine ligand containing complex 1 was converted to the phosphine oxide ligand containing complex 2 in air in acetonitrile solution. Both complexes 1 and 2 were investigated as precatalysts for alcohol dehydrogenation-triggered synthesis of imines in air. The phosphine-oxide complex 2 was more efficient than the phosphine complex 1. A wide array of alcohols and amines were successfully reacted in a mild condition to result in imines in good to excellent yields. Precatalyst 2 was also highly efficient for the synthesis of varieties of quinolines in air. As H2L2 in 2 has side arms that can be deprotonated, we investigated complex 2 for its base (KOtBu) promoted deprotonation events by various spectroscopic studies and DFT calculations. These studies have shown that mono deprotonation of the amine side arm attached to the pyridine is quite feasible, and deprotonation of complex 2 leads to a dearomatized pyridyl ring containing complex 2a. The mechanistic investigations of the catalytic reaction, by a combination of experimental and computational studies, have suggested that the dearomatized complex, 2a acted as an active catalyst. The reaction proceeded through the hydride transfer pathway. The activation barrier of this step was calculated to be 26.5 kcal/mol, which is quite consistent with the experimental reaction temperature under aerobic conditions. Although various pincer-like complexes are explored for such reactions, phosphine oxide ligand-containing complexes are still unexplored.

Visible-Light-Sensitive Photoliquefiable Arylazoisoxazoles for the Solar Energy Conversion, Storage and Controlled-Release of Heat at Room Temperature or Lower Temperatures.

The photoswitchable MOlecular Solar Thermal (MOST) energy storage systems that are capable of exhibiting high energy storage densities are found to suffer from the poor cyclability, the use of less abundant UV light of the solar spectrum, or reduced charging/discharging rates and poor photoconversions in solid states. Herein, we have designed and readily synthesized a novel set of para-thioalkyl substituted arylazoisoxazoles, that undergo high trans-cis and cis-trans photoconversions under visible light, and show fast charging/discharging and impressive cyclability. Remarkably, the presence of C6-or C10-thioalkyl chainin photochromes permitted reversible solid-liquid phase transition with the formation of cis-enriched charged states by 400 nm light irradiation and trans-enriched discharged states by 530 nm light at various temperatures (10-35 °C). The solid-to-liquid phase transition enabled storage of the latent heat in addition to the isomerization energy, resulting in a high net energy storage density of 189-196 J/g, which are substantially higher than that of many recently reported azobenzene-based MOST compounds (100-161 J/g). Using a high-resolution infrared camera, we further demonstrated that a brief irradiation of green light can be employed to readily release the trapped photon energy as heat. Our results suggest that the arylazoisoxazole with C6-thioalkyl chain at para-position can serve as an effective and eco-friendly photoliquefiable MOST material.

Photoisomerization and Light-Controlled Antibacterial Activity of Fluoroquinolone-Azoisoxazole Hybrids.

Photopharmacology holds a huge untapped potential to locally treat diseases involving photoswitchable drugs via the elimination of drugs' off-target effects. The growth of this field has created a pressing demand to develop such light-active drugs. We explored the potential for creating photoswitchable antibiotic hybrids by attaching pharmacophores norfloxacin/ciprofloxacin and azoisoxazole (photoswitch). All compounds exhibited a moderate to a high degree of bidirectional photoisomerization, long thermal cis half-lives, and impressive photoresistance. Gram-negative pathogens were found to be insensitive to these hybrids, while against Gram-positive pathogens, all hybrids in their trans states exhibited antibacterial activity that is comparable to that of the parent drugs. Notably, the toxicity of the irradiated hybrid 6 was found to be 2-fold lower than the nonirradiated trans isomer, indicating that the pre-inactivated cis-enriched drug can be employed for the site-specific treatment of bacterial infection using light, which could potentially eliminate the unwanted exposure of toxic antibiotics to both beneficial and untargeted harmful microbes in our body. Molecular docking revealed different binding affinity of the cis and trans isomers with the topoisomerase IV enzyme, due to their different shapes.

Direct Growth Control of Antibiotic-Resistant Bacteria Using Visible-Light-Responsive Novel Photoswitchable Antibiotics.

In addition to the discovery of new (modified) potent antibiotics to combat antibiotic resistance, there is a critical need to develop novel strategies that would restrict their off-target effects and unnecessary exposure to bacteria in our body and environment. We report a set of new photoswitchable arylazopyrazole-modified norfloxacin antibiotics that present a high degree of bidirectional photoisomerization, impressive fatigue resistance and reasonably high cis half-lives. The irradiated isomers of most compounds were found to exhibit nearly equal or higher antibacterial activity than norfloxacin against Gram-positive bacteria. Notably, against norfloxacin-resistant S. aureus bacteria, the visible-light-responsive p-SMe-substituted derivative showed remarkably high antimicrobial potency (MIC of 0.25 µg/mL) in the irradiated state, while the potency was reduced by 24-fold in case of its non-irradiated state. The activity was estimated to be retained for more than 7 hours. This is the first report to demonstrate direct photochemical control of the growth of antibiotic-resistant bacteria and to show the highest activity difference between irradiated and non-irradiated states of a photoswitchable antibiotic. Additionally, both isomers were found to be non-harmful to human cells. Molecular modellings were performed to identify the underlying reason behind the high-affinity binding of the irradiated isomer to topoisomerase IV enzyme.

Noninnocent Azo-Aromatic Cobalt(II)-Catalyzed sp3 C-H Alkylation of Fluorenes with Alcohols.

Herein, employing well-defined redox noninnocent cobalt(II) complexes an efficient sp3 C-H alkylation of fluorenes using alcohols as alkylating agents to result in alkylated fluorenes is reported. The catalytic protocol was versatile with various fluorenes and benzyl alcohols. It also showed very good functional group tolerance with both alcohols and fluorenes. Moreover, an efficient single-step and simultaneous di C-C as well as both C-C and the C-N alkylation reaction of fluorenes was observed with this catalytic protocol. Such selective single-step dialkylation of fluorenes is indeed beneficial. Several control experiments, deuterium labeling, and 1H NMR kinetic studies have revealed a ligand radical-based borrowing hydrogen mechanism involving the azo-aromatic complexes of cobalt as catalysts for the alkylation of fluorenes.

Photoswitchable Antibiotic Hybrids: Spacer Length-Dependent Photochemical Control of Antibacterial Activity.

Photopharmacology holds huge potential for the permanent (long-term) eradication of antibiotic resistance by the application of photoswitchable antibiotics. To construct such antibiotics, various methods have been employed to modify known antibiotics with photoswitches, such that the irradiated state shows activity comparable to or higher than that of the parent antibiotic and that a large activity difference between irradiated and nonirradiated states is achieved. However, most of those methods are ineffective when dealing with more than one drug with dissimilar structures. Here, we have demonstrated a new approach, in which two pharmacophores, one being a photoswitch, are covalently linked via a spacer of variable lengths, leading to a set of azopyrazole-norfloxacin antibiotic hybrids. All compounds showed a high degree of bidirectional photoisomerization, long thermal cis half-lives, and excellent photoresistance. Notably, the hybrid with an optimal four-carbon spacer length enabled the irradiated state to become 12-fold more potent than its nonirradiated state without losing much antimicrobial activity of norfloxacin. Only Gram-positive bacteria were found to be sensitive to this hybrid, and the full antibacterial potency of its irradiated state was found to be retained for nearly 24 h.

Genetically Encoded Aminocoumarin Lysine for Optical Control of Protein-Nucleotide Interactions in Zebrafish Embryos.

The strategic placement of unnatural amino acids into the active site of kinases and phosphatases has allowed for the generation of photocaged signaling proteins that offer spatiotemporal control over activation of these pathways through precise light exposure. However, deploying this technology to study cell signaling in the context of embryo development has been limited. The promise of optical control is especially useful in the early stages of an embryo where development is driven by tightly orchestrated signaling events. Here, we demonstrate light-induced activation of Protein Kinase A and a RASopathy mutant of NRAS in the zebrafish embryo using a new light-activated amino acid. We applied this approach to gain insight into the roles of these proteins in gastrulation and heart development and forge a path for further investigation of RASopathy mutant proteins in animals.

Photoisomerization of 2-Arylazoimidazoles under Visible Light: Identifying a Predictive Tool to Anticipate and Tune Likely Photoswitching Performance and Cis Half-Life.

Azopyrazoles are an emerging class of photoswitches, whereas analogous azoimidazole-based switches are unable to draw much attention because of their short cis half-lives, poor cis-trans photoreversion yields, and toxic ultraviolet (UV) light-assisted isomerization. A series of 24 various aryl-substituted N-methyl-2-arylazoimidazoles were synthesized, and their photoswitching performances and cis-trans isomerization kinetics were thoroughly investigated experimentally and theoretically. Para-π-donor-substituted azoimidazoles with highly twisted T-shaped cis conformations showed nearly complete bidirectional photoswitching, whereas di-o-substituted switches exhibited very long cis half-lives (days-years) with nearly ideal T-shaped conformations. This study demonstrates how the electron density in the aryl ring affects cis half-life and cis-trans photoreversion via twisting of the NNAr dihedral angle that can be used as a predictive metric for envisaging and tuning the likely switching performance and half-life of any given 2-arylazoimidazole. By applying this tool, two better-performing azoimidazole photoswitches were engineered. All switches permitted irradiation by violet (400-405 nm) and orange (>585 nm) light for forward and reverse isomerization, respectively, and displayed comparatively high quantum yields and impressive resistance to photobleaching.

Completely o-Phenylene Bridged N4-Cyclophane: A Missing Link in the Phenylene Bridge N4-Cyclophane Family.

Unprecedented types of metal-free complete o-phenylene bridged N4-cyclophanes (M1 and M2) have been synthesized via sequential palladium-catalyzed Buchwald-Hartwig N-arylation reactions. These cyclophanes may be considered as aromatic analogues of aliphatic group-spaced N4-macrocycles. These have been characterized fully using physicochemical characterization techniques and finally by single crystal X-ray structure determination. Their redox and spectral properties have been characterized by cyclic voltammetry, UV-vis spectro-electrochemistry, fluorescence spectral studies, and DFT calculations. These studies have shown rich redox, spectral, and photophysical properties that could make both M1 and M2 potential candidates for various applications.

Alcohol Dehydrogenation-Triggered Selective C3-Alkylation of Indoles by Homogeneous Azo-aromatic Cobalt Catalysts.

Herein, we report azo-benzimidazole containing cobalt complexes (1-3) for alcohol dehydrogenation-triggered C3-alkylation of indoles. In complexes 1-3, ligands are redox noninnocent and showed facile irreversible L/L• reduction followed by Co(II)/Co(I) reduction in close-lying potentials. Taking advantage of facile redox events in 1-3, the first aerial dehydrogenation of alcohols to their corresponding carbonyl compounds is explored. Subsequently, C3-alkylation of indole was studied using alcohols as the alkylating agents. The developed catalytic protocol was found to be efficient and very selective. It has a broad substrate scope and good functional group tolerance. As far as we are aware, it is the first homogeneous cobalt catalyst for C3-alkylation of indole using alcohol as the alkylating agent. Detailed mechanistic studies, including a deuterium labeling experiment, have suggested a borrowing hydrogen method for the C3-alkylation of indole. The coordinated ligand, cooperatively with the Co(II)/Co(I) redox couple, oxidized the coordinated alkoxide in a radical pathway to result in the carbonyl compound (Scheme 1), which on subsequent condensation with indole generates the alkylideneindolenine intermediate "X". Reduction of "X" by an azo-anion radical Co(I) catalyst intermediate resulted in the C3-alkylated indole.

Hemilabile Amine-Functionalized Efficient Azo-Aromatic Cu-Catalysts Inspired by Galactose Oxidase: Impact of Amine Sidearm on Catalytic Aerobic Oxidation of Alcohols.

A series of azo-aromatic copper(II) complexes, [1a-g] and a Cu(I) complex, [1h], with varying amine-functionalized hemilabile pincer-like [HL1-3] and [L1,2], methyl-substituted azo [L3], and imine [L4] ligands, were synthesized and characterized. These complexes were investigated for aerobic oxidation of a variety of aromatic alcohols in the presence of 2.0 mol % precatalysts [1a-g], cobaltocene (2.0 mol %), N-methyl imidazole (NMI) (8.0 mol %), and TEMPOH (2.0 mol %) at room temperature. The Cu(I) complex (1h) acted as a catalyst in the absence of cobaltocene. To understand the mechanism, detailed experimental and theoretical studies have been performed with the representative complex [1a], which has suggested a new kind of mechanism involving a Cu(II)/Cu(I) redox couple. Cobaltocene acts as a reductant to [1a] to generate a Cu(I) complex, which activates dioxygen in the presence of NMI. TEMPOH transfers a hydrogen atom to the activated dioxygen with the generation of TEMPO•, which further participates in α-C-H bond activation in the Cu(II)-alkoxide intermediate in an intermolecular fashion in the catalytic cycle. The amine sidearm in the ligand backbone of the complexes has a significant role in catalytic activity. Complexes with amine sidearms are more effective than complexes without them. Moreover, the aliphatic secondary amine sidearm is more efficient among the amine sidearm than the aromatic secondary amine and tertiary amines. The amine sidearm that remained coordinated to the Cu(II) center is hemilabile, and it facilitates alcohol coordination in the catalytic process. Alcohol coordination was the rate-limiting step, and it was supported by the isotope effect study on benzyl alcohol, substitution effect on the amine moiety of the ligands, and DFT calculation. The hemilabile amine sidearm of the coordinated ligand also acted as a base in deprotonating the alcoholic O-H proton and acted as an acid in releasing H2O2 during the catalysis.

Near-Complete Bidirectional Photoisomerization of para-Dialkylamino-Substituted Arylazopyrazoles under Violet and Green or Red Lights.

para-Dimethylamine- and para-pyrrolidine-substituted arylazopyrazoles display very high to near-quantitative or quantitative bidirectional isomerization under violet and green or red lights in both polar (DMSO and DMSO/aqueous buffer, pH 7.5) and nonpolar solvents. These switches confer a reasonable thermal stability to their cis-states (t1/2 ≈ 4-7 h in DMSO and DMSO/buffer) and also show a high level of resistance to photobleaching and an impressive stability to reduction by glutathione. Using DFT calculations, attempts have been made to decipher the photophysical properties and thermal stabilities of the cis isomers.

Polymerisation of styrene using pincer type amine functionalized azo aromatic complexes of Co(II) as catalysts.

In the present report, three mononuclear azo-aromatic complexes of Co(II), 1-3, and an imine-based Co(II) complex, 4, were synthesized through a reaction of respective amine-functionalized pincer-like ligands, HL1-4, with CoCl2·6H2O in the ligand-to-metal ratio of 1 : 1. All the complexes, 1-4, were thoroughly characterized using various physicochemical characterization techniques, single-crystal X-ray structure determination, and density functional theory (DFT) calculations. Complexes 1-4 were explored for the catalytic styrene polymerisation reaction separately in the presence of modified methyl aluminoxane (MMAO). All the complexes, 1-4, are indeed active for the polymerisation of styrene under mild conditions at room temperature upon activation with MMAO. Among the azo-aromatic complexes 1-3, complex 3 is the most efficient. The activity of the imine complex 4 is poor compared to those of the azo-aromatic complexes 1-3. The weight average molecular weight (Mw) of the isolated polystyrene ranges from 32.9 to 144.0 kg mol-1, with a polydispersity index (D) in the range of 1.1-1.8. Microstructural analysis of the isolated polymer from complexes 1-4 was carried out by 13C NMR spectroscopy, infrared spectroscopy, and powder X-ray diffraction studies. Their thermal properties were scrutinized by differential scanning calorimetry and thermogravimetric analysis. These studies have shown the atactic and amorphous nature of the polymers. The mechanical strength of the polymers was measured by a nanoindentation technique which has shown the good plastic/soft nature of the polymers.

Azide-Alkyne "Click" Reaction in Water Using Parts-Per-Million Amine-Functionalized Azoaromatic Cu(I) Complex as Catalyst: Effect of the Amine Side Arm.

A series of Cu(II) complexes, 1-4 and 6, were synthesized through a reaction of amine-functionalized pincer-like ligands, HL1,2, La,b, and a bidentate ligand L1 with CuCl2·2H2O. The chemical reduction of complex 1 using 1 equiv of sodium l-ascorbate resulted in a dimeric Cu(I) complex 5 in excellent yield. All of the complexes, 1-6, were thoroughly characterized using various physicochemical characterization techniques, single-crystal X-ray structure determination, and density functional theory calculations. Ligands HL1,2 and La,b behaved as tridentated donors by the coordination of the amine side arm in their respective Cu(II) complexes, and the amine side arm remained as a pendant in Cu(I) complexes. All of these complexes (1-6) were explored for copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) reaction at room temperature in water under air. Complex 5 directly served as an active catalyst; however, complexes 1-4 and 6 required 1 equiv of sodium l-ascorbate to generate their corresponding active Cu(I) catalyst. It has been observed that azo-based ligand-containing Cu(I)-complexes are air-stable and were highly efficient for the CuAAC reaction. The amine side arm in the ligand backbone has a dramatic role in accelerating the reaction rate. Mechanistic investigations showed that the alkyne C-H deprotonation was the rate-limiting step and the pendant amine side arm intramolecularly served as a base for Cu-coordinated alkyne deprotonation, leading to the azide-alkyne 2 + 3 cycloaddition reaction. Thus, variation of the amine side arm in complexes 1-4 and use of the most basic diisopropyl amine moiety in complex 4 has resulted in an unique amine-functionalized azoaromatic Cu(I) system for CuAAC reaction upon sodium l-ascorbate reduction. The complex 4 has shown excellent catalysis at its low parts-per-million level loading in water. The catalytic protocol was versatile and exhibited very good functional group tolerance. It was also employed efficiently to synthesize a number of useful functional triazoles having medicinal, catalytic, and targeting properties.

Irreversible Resistive State Switching in Devices with a Homoleptic Cobalt(II) Complex Active Layer.

Molecules with bi-stable electronic transport behaviour have been in upfront research topics of the molecular semiconductor devices in the past few decades due to the use of such materials in resistive data storage devices. Transition metal complexes (TMC) are expected to be potential candidates in regard to the tunable and manifold redox behaviour expecting multiple bulk transport states. Finding alternate mechanisms in such devices with TMC as the active layer materials would revoke the multifaceted approach to the functional gain. We have succeeded in demonstrating write once-read many (WORM) type of resistive memory device using a homoleptic Cobalt(II) (Co(II)) complex with large on/off current ratio ensuring the easy readout process at lower voltage. The advantage of this device was the turn on voltage was found to be the low (<2.7 V) operational voltage and the success ratio of the devices were more than 83%. The durability of the stored data was found to be more than 35,000 seconds which ensures the stability of the bistable state in the fabricated devices. Such ambient stable, solution processable devices are important for the large-scale printable devices. The manuscript describes the preparation, optical and electrochemical characterisation of the metal complex used along with a detailed mechanistic investigations and electrical characterisation of memory device obtained from a stable cobalt complex.

Robust bi-directional photoswitching of thiomethyl substituted arylazopyrazoles under visible light.

Mono-ortho- and para-thiomethyl-substituted arylazopyrazoles show substantial absorbance in visible wavelengths, enabling very high to near-quantitative forward and reverse isomerization in DMSO and aqueous solution by visible light. cis isomers display excellent thermal stability (∼3 days, 27 °C). Additionally, these switches possess good photostability and are resistant to reduction by glutathione.

Dehydrogenation of amines in aryl-amine functionalized pincer-like nitrogen-donor redox non-innocent ligands via ligand reduction on a Ni(ii) template.

We have synthesized a series of new redox non-innocent azo aromatic pincer-like ligands: 2-(phenylazo)-6-(arylaminomethyl)pyridine (HLa-c: HLa = 2-(phenylazo)-6-(2,6-diisopropylphenylaminomethyl)pyridine, HLb = 2-(phenylazo)-6-(2,6-dimethylphenylaminomethyl)pyridine, and HLc = 2-(phenylazo)-6-(phenylaminomethyl)pyridine), in which one side arm is an arylaminomethyl moiety and the other arm is a 2-phenylazo moiety. Nickel(ii) complexes, 1-3, of these ligands HLa-c were synthesized in good yield (approximately 70%) by the reaction of ligands : (NiCl2·6H2O) in a 1 : 1 molar ratio in methanol. The amine donor in each of the ligands HLa-c binds to the Ni(ii) centre without deprotonation. In the solid state, complex 3 is a dimer; in solution it exists as monomer 3a. The reduction of acetonitrile solutions of each of the complexes 1, 2 and 3a, separately, with cobaltocene (1 equivalent), followed by exposure of the solution to air, resulted in the formation of new complexes 7, 8 and 9, respectively. Novel free ligands Lx and Ly have also been isolated, in addition to complexes 7 and 8, from the reaction of complexes 1 and 2, respectively. Complexes 7-9 and free ligands Lx and Ly have been formed via a dehydrogenation reaction of the arylaminomethyl side arm. The mechanism of the reaction was thoroughly investigated using a series of studies, including cyclic voltammetry, EPR, and UV-Vis spectral studies and density functional theory (DFT) calculations. The results of these studies suggest a mechanism initiated by ligand reduction followed by dioxygen activation. A Cl-/I- scrambling experiment revealed that the dissociation of the chloride ligand(s) was associated with the one-electron reduction of the ligand (azo moiety) in each of the complexes 1, 2 and 3a. The dissociated chloride ligand(s) were reassociated with the metal following the dehydrogenation reaction to yield the final products. All of the newly synthesized compounds were fully characterized using a variety of physicochemical techniques. Single-crystal X-ray structures of the representative compounds were determined to confirm the identities of the synthesized molecules.

Reversible and Tunable Photoswitching of Protein Function through Genetic Encoding of Azobenzene Amino Acids in Mammalian Cells.

The genetic encoding of three different azobenzene phenylalanines with different photochemical properties was achieved in human cells by using an engineered pyrrolysyl tRNA/tRNA synthetase pair. In order to demonstrate reversible light control of protein function, azobenzenes were site-specifically introduced into firefly luciferase. Computational strategies were applied to guide the selection of potential photoswitchable sites that lead to a reversibly controlled luciferase enzyme. In addition, the new azobenzene analogues provide enhanced thermal stability, high photoconversion, and responsiveness to visible light. These small-molecule photoswitches can reversibly photocontrol protein function with excellent spatiotemporal resolution, and preferred sites for incorporation can be computationally determined, thus providing a new tool for investigating biological processes.

Effects of Ancillary Ligands on Redox and Chemical Properties of Ruthenium Coordinated Azoaromatic Pincer.

In this work, the effect of the electronically different ancillary ligands on the overall properties of the RuIIL moiety (L = 2,6-bis(phenylazo)pyridine) in heteroleptic complexes of general formula [RuLQCl]0/+ was investigated. Four different ancillary ligands (Q) with different electronic effects were used to prepare the heteroleptic compounds from the precursor complex, [RuL(CH3CN)Cl2] (1); Q = pcp: 2-(4-chloro-phenylazo)pyridine (strong π-acceptor), [2]+; bpy: 2,2'-bipyridyl (moderate π-acceptor), [3]+; acac-: acetylacetonate (strong σ-donor), 4; and DTBCat2-: 3,5-di- tert-butyl catecholate (strong π-donor), 5. The complexes [2]+, [3]+, 4, and 5 were fully characterized and structurally identified. The electronic structures of these complexes along with their redox partners were elucidated by using a host of physical measurements: nuclear magnetic resonance, cyclic voltammetry, electronic paramagnetic resonance, UV-vis-NIR spectroscopy, and density functional theory. The studies revealed significant effects of the coligands on azo bond lengths of the RuL moiety and their redox behavior. Aerobic alcohol oxidation reactions using these Ru complexes as catalysts were scrutinized. It was found that the catalytic efficiency is primarily controlled by the electronic effect of the coligand. Accordingly, the complex [2]+ (containing a strong π-acceptor coligand, pcp) brings about oxidation efficiently, producing 86% of benzaldehyde. In comparison, however, the complexes 4 and 5 (containing electron donating coligand) furnished only 15-20% of benzaldehyde under identical reaction conditions. Investigations of the reaction mechanism suggest that an unstable Ru-H species is formed, which is transformed to a Ru-hydrazo intermediate by H-walking as reported by Hall et al. ( J. Am. Chem. Soc., 2015, 137, 12330). Aerial O2 regenerates the catalyst via oxidation of the hydrazo intermediate.