Hydroxy Moiety Research Articles

Two-Step Synthesis of Enantiomerically Pure Morphans from (R)-Carvone.

Enantiomerically pure 4-hydroxymorphan-7-ones were prepared in two steps from the natural product (R)-carvone. At first, the isopropenyl moiety of (R)-carvone was converted into the epoxide 7. A Domino reaction consisting of epoxide opening with primary amines followed by intramolecular conjugate addition of the resulting secondary amines at the α,β-unsaturated ketone established the morphan scaffold. This novel morphan synthesis allowed the modification of the bicyclic system at three positions resulting in 26 diverse morphans. Various primary amines led to morphans 8-13 with different N-substituents. Acylation or water elimination followed by hydrogenation led to esters 15 and 16 or the morphan 18 without a hydroxy moiety. The benzylidenemorphans 25a and 26a were prepared by condensation of the ketones 11a and 12a with benzaldehyde. Finally, the α-methylene ketone of 11a and 12a was exploited to obtain indolomorphans, quinolinomorphans, pyrimidinomorphans and pyrazolomorphans. Affinity of the novel morphans at opioid receptors MOR, DOR and KOR could not be detected. However, the indolomorphan 19 and the quinolinomorphan 22 showed nanomolar σ1 receptor affinity (Ki=58 nM and 20 nM).

Construction of HaloTag-based macromolecular probe for multiple logic gates and photoactivatable bioimaging

Protein bioconjugation has emerged as one of the most valuable tools for the development of protein-based biochemical assays. Herein, we report a fluorescent macromolecular probe RF12_POI, in which the coumarin derivative RF12 is specifically conjugated onto the HaloTag fused protein of interest (POI) to achieve a dual stimuli-mediated fluorescence response. RF12 is first obtained by installing a photo-cleavable 1-ethyl-2-nitrobenzyl group onto the C7 hydroxy moiety of coumarin fluorophore with a HaloTag ligand attaching to the acid-labile 1,3-dioxane moiety. Upon stimulation, RF12_Halo exhibits a sequential fluorescence response to photon/H+ on both liquid and solid interfaces. Through the conjugation of RF12 onto the GFP_Halo protein, RF12_GFP_Halo presents a fluorescence resonance energy transfer (FRET) from photo-cleaved RF12 to GFP in the protein complex. Furthermore, by utilizing the stimuli-responsive fluorescence characteristics of coumarin derivatives RF12 (photon/H+) and RF16 (H2O2/H+), we construct RF12/RF16_POI based protein films and achieve multiple applications of logic circuits, including AND, OR, XOR, INHIBIT, Half-adder or Half-subtractor. In these circuits, the output value of I/I0 is dependent on the input sequence of photon, H2O2, and H+. Additionally, we evaluate the fluorescence labeling ability of RF12 to intracellular IRE1_Halo protein and demonstrate that RF12 containing the HaloTag ligand could be precisely retained in cells to track IRE1_Halo protein. Hence, we provide a unique structural design strategy to construct fluorescence dual-responsive macromolecules for information encryption and cellular protein visualization.

Computational Investigation about the Effects of Solvent Polarity and Chalcogen Element Electronegativity on ESIPT Behaviors for the Et2N-Substituted Flavonoid.

Inspired by the outstanding nature of flavonoid derivatives in the fields of chemistry and medicine, in this work we mainly focus on exploring the photo-induced properties of the novel Et2N-substituted flavonoid (ENF) fluorophore theoretically. Considering the potential photo-induced properties in different solvents and the chalcogen atomic electronegativity-associated photoexcitation, by time-dependent density functional theory (TDDFT) methods we primarily explore the intramolecular hydrogen bonding interactions and photo-induced charge redistribution behaviors. Via comparing geometrical data and the infrared (IR) spectral shifts-associated hydroxy moiety of ENF, we confirm that the intramolecular hydrogen bond O-H···O should be enhanced with facilitating an excited-state intramolecular proton-transfer (ESIPT) reaction. Particularly, the charge reorganization around hydrogen bonding moieties further reveals the tendency of ESIPT behavior. Combined with the construction of the potential energy surface and the search for reaction transition states, we finally confirmed the solvent-polarity-regulated behaviors as well as the chalcogen elements' electronegativity-dependent ESIPT mechanisms for the ENF fluorophore. We sincerely wish our work could accelerate the further development and applications of flavonoid derivatives.

Efficient Reductive N-11C-Methylation Using Arylamines or Alkylamines and InSitu-Generated [11C]Formaldehyde From [11C]Methyl Iodide.

Reductive N-11C-methylation using [11C]formaldehyde and amines has been used to prepare N-11C-methylated compounds. However, the yields of the N-11C-methylated compounds are often insufficient. In this study, we developed an efficient method for base-free reductive N-11C-methylation that is applicable to a wide variety of substrates, including arylamines bearing electron-withdrawing and electron-donating substituents. A 2-picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N-11C-methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N-11C-methylation generally increased the yield of the N-11C-methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N-11C-methylation should be applicable to a wide variety of substrates, including thermo-labile and base-sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.

Design of Reversible Adhesives by Using a Triple Function of Ionic Liquids

AbstractReversible adhesives are crucial for a circular economy of composites as they play a key role for rework, repair, and recycling of adhesively bonded components. Herein, electrically debondable adhesives are prepared by introducing ionic liquids in dynamic thiol–epoxy networks. The function of the ionic liquid in the networks is threefold as it accelerates the curing reaction between thiol and epoxy monomers, facilitates electrical debonding, and catalyzes thermoactivated transesterification reactions, required for rebonding at elevated temperature. A library of 1,3‐dibutylimidazolium‐based ionic liquids with varying anions is synthetized and it is found that 1,3‐dibutyl‐1H‐imidazol‐3‐ium dicyanamide (DiButIm─N(CN)2) is superior in accelerating bond‐exchange reactions between hydroxy and ester moieties at elevated temperature. Thus, a thiol–epoxy resin containing 20 wt% of DiButIm─N(CN)2 is used to impregnate glass fiber mats yielding adhesive connections for aluminum substrates with 10.2 MPa pull‐off strength. The adhesive connections are successfully debonded at the metal–adhesive interface by applying 120 V. The samples are then rebonded via the thermoactivated change in the networks’ viscoelastic properties and ≈80% (8.1 MPa) of their original bond strength can be regained. By providing a simple strategy to synthetize reversible adhesives, this approach paves a way toward improved recyclability and repairability of adhesively bonded structures.

Unveiling the potential of alginate-based nanomaterials in sensing technology and smart delivery applications.

Sensors are applied to many fields nowadays because of their high sensitivity, low cost, time-saving, user-friendly, and excellent selectivity. Current biomedical and pharmaceutical science has one focus on developing nanoparticle-based sensors, especially biopolymeric nanoparticles. Alginate is a widely used biopolymer in a variety of applications. The hydrogel-forming characteristic, the chemical structure with hydroxy and carboxylate moieties, biocompatibility, biodegradability, and water solubility of alginate have expanded opportunities in material and biomedical sciences. Recently, research on alginate-based nanoparticles and their applications has begun. These materials are gaining popularity because of their wide usage potential in the biomedical and pharmaceutical fields. Many review papers describe applications of alginate in the drug delivery field. The current study covers the structural and physicochemical properties of alginate-based nanoparticles. The prospective applications of alginate-based nanomaterials in various domains are discussed, including drug delivery and environmental sensing applications for humidity, heavy metals, and hydrogen peroxide. Moreover, biomedical sensing applications of alginate-based nanoparticles regarding various analytes such as glucose, cancer cells, pharmaceutical drugs, and human motion will also be reviewed in this paper. Future research scopes highlight existing challenges and solutions.

Phenol is a pH-activated linker to gold: a single molecule conductance study.

Single molecule conductance measurements typically rely on functional linker groups to anchor the molecule to the conductive electrodes through a donor-acceptor or covalent bond. While many linking moieties, such as thiols, amines, thiothers and phosphines have been used among others, very few involve oxygen binding directly to gold electrodes. Here, we report successful single molecule conductance measurements using hydroxy (OH)-containing phenol linkers and show that the molecule-gold attachment and electron transport are mediated by a direct O-Au bond. We find that deprotonation of the hydroxy moiety is necessary for metal-molecule binding to proceed, so that junction formation can be activated through pH control. Electronic structure and DFT+Σ transport calculations confirm our experimental findings that phenolate-terminated alkanes can anchor on the gold and show charge transport trends consistent with prior observations of alkane conductance with other linker groups. Critically, the deprotonated O--Au binding shows features similar to the thiolate-Au bond, but without the junction disruption caused by intercalation of sulfur into electrode tips often observed with thiol-terminated molecules. By comparing the conductance and binding features of O-Au and S-Au bonds, this study provides insight into the aspects of Au-linker bonding that promote reproducible and robust single molecule junction measurements.

Coumarin-Conjugated Macromolecular Probe for Sequential Stimuli-Mediated Activation.

Protein bioconjugation has emerged as one of the most valuable tools for the development of protein-based biochemical assays. Here, we report a fluorescent macromolecular material, RF16_Halo, in which the coumarin derivative RF16 is specifically conjugated onto HaloTag protein to achieve a dual-stimuli-mediated fluorescence response. RF16 is first obtained by installing a H2O2-sensitive boron cage onto the C7 hydroxy moiety of the coumarin fluorophore with a HaloTag ligand attaching to the pH-labile 1,3-dioxane moiety. Upon stimulation, RF16_Halo exhibits a sequential fluorescence response to H2O2/pH at both liquid and solid interfaces. The fluorescence of the RF16_Halo-based protein film increases linearly toward H2O2 with a higher sensitivity when compared with that of RF16. Subsequently, the H2O2-cleaved RF16_Halo presents a pH-dependent fluorescence decrease under acidic conditions. Such a stimulus-responsive fluorescence "off-on-off" multimode enables RF16_Halo to be applied as a sequential logic circuit. In addition, we evaluate the fluorescence labeling ability of RF16 to intracellular IRE1_Halo protein and demonstrate that RF16 containing the HaloTag ligand could be precisely retained in cells to track IRE1_Halo protein. Hence, we provide a unique structural design strategy to construct a fluorescence dual-responsive macromolecular probe for information encryption and protein tracking in cells.

Polydopamine-functionalized electrospun poly(vinyl alcohol)/chitosan nanofibers for the removal and determination of Cu(II)

Environmentally friendly and recycled polydopamine-functionalized electrospun poly(vinyl alcohol)/chitosan nanofibers (PVA/CS/PDA) were prepared through a low-energy-consumption procedure. The PDA coating endows PVA/CS/PDA nanofibers with good water stability. The PVA/CS/PDA nanofibers have a fibrillar and porous structure that is favorable for Cu(II) to access the active sites of the nanofibers. The adsorption isotherm and kinetics data preferably conform to the Liu isotherm and pseudo-second-order kinetic models, respectively. The maximum adsorption capacity of Cu(II) ions by PVA/CS/PDA nanofibers from the Liu isotherm model is 326.5 mg g−1. The PVA/CS/PDA nanofibers exhibit higher adsorption capacity than some other reported adsorbents. The adsorption mechanism study demonstrates that the Cu(II) adsorption is mainly ascribed to the complexation of Cu(II) with the imino, amino, and hydroxy moieties in PVA/CS/PDA nanofibers. The nanofibers can be employed for 5 cycles without significantly deteriorating performance. More interestingly, a fluorometry method based on the oxidation mimic enzyme activity of Cu(II) was developed to detect low concentrations of Cu(II) using the nanofibers as an adsorbent to preconcentrate Cu(II). The limit of detection is 0.42 mg L−1. The successful removal and detection of Cu(II) in Pearl River and mineral water samples demonstrates the great potential of PVA/CS/PDA nanofibers to remediate Cu(II)-polluted water.

On-demand Activation of Transesterification via Chemical Amplification in Dynamic Thiol-ene Photopolymers.

Chemical amplification is a well-established concept in photoresist technology, wherein one photochemical event leads to a cascade of follow-up reactions facilitating a controlled change in the solubility of a polymer. Herein, we transfer this concept to dynamic polymer networks to liberate both catalyst and functional groups required for bond exchange reactions via UV irradiation. For this, we exploit a photochemically-generated acid to catalyse a deprotection reaction of an acid-labile tert-butoxycarbonyl group, which is employed to mask the hydroxy groups of a vinyl monomer. At the same time, the released acid serves as a catalyst for thermo-activated transesterifications between the deprotected hydroxyl and ester moieties. Introduced in an orthogonally-cured (450 nm) thiol-click photopolymer, this approach allows for a spatio-temporally controlled activation of bond exchange reactions, which is crucial in light of the creep resistance vs reflow ability trade-off of dynamic polymer networks.

UV-Vis spectroscopic and colorimetric anion detection and fluorescence properties of new 3-amino-4-hydroxybenzenesulfonic acid-based Schiff bases depending on the strength and position of the electron donor substitution

In this study, 3-amino-4-hydroxybenzenesulfonic acid-based imine compounds; 3-(2,5-dihydroxybenzylideneamino)-4-hydroxybenzenesulfonic acid (1), 3-(2,4-dihydroxybenzylideneamino)-4-hydroxybenzenesulfonic acid (2) and 4-hydroxy-3-(2-hydroxy-3-methoxybenzylideneamino)-4-hydroxybenzenesulfonic acid (3) was synthesized. The compounds were analyzed using various spectroscopy methods, and the experimental UV–vis data matched the theoretical predictions. The compound 1 displayed lower stability, higher reactivity, and easier photoexcitation due to a smaller HOMO-LUMO energy gap. The investigated compounds 1-3 showed promise as chemosensors for anions, providing visible detection in daylight conditions. The compound 3 exhibited selective fluorescence at specific wavelengths. The compounds 1-3 interacted with DNA through electrostatic interactions. Also, compounds 1-3 showed higher antioxidant activity than BHT. However, fluorescence measurements indicated that the emission signals were strongly influenced by the position and strength of the electron-donating group. Adding a hydroxy or methoxy moiety near the -OH group on the phenyl ring decreased the fluorescence signal due to intersystem crossing and intramolecular charge transfer mechanisms, respectively. These findings were supported by femtosecond transient absorption spectroscopy measurements. The results emphasize the significance of substituents in imines derived from 3-amino-4-hydroxybenzenesulfonic acid in determining their biological activities, as well as their optical and sensor properties.

Synthesis and structure-activity relationship studies of naphthoquinones as STAT3 inhibitors

Based on previous studies, we synthesized a novel class of ortho- and para-naphthoquinones derivatives bearing a phenolic hydroxy or sulfonamide moiety and evaluated their in vitro antiproliferative and signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitory activities. The biological evaluations of these naphthoquinones revealed that ortho-naphthoquinones containing a phenolic hydroxyl group exhibited greater antiproliferative activity compared to compounds without a phenolic hydroxyl group. Among the synthesized para-naphthoquinones, 21, which has a condensed sulfonamide structure, showed substantially higher antiproliferative activity than that of the parent compound, and was also found to inhibit the phosphorylation of STAT3(Y705) in a dose-dependent manner. A docking simulation using AutoDock Vina suggested that 21 could directly bind to the hinge region of STAT3.

Electrochemical oxidation of sec-alcohols with MgBr2·6H2O

The electrochemical oxidation of sec-alcohols has been achieved using MgBr2·6H2O as an inexpensive active bromine source and electrolyte under constant current conditions. The reactions smoothly proceed in a simple undivided cell, and aliphatic/benzylic sec-alcohols bearing heteroaromatics as well as aryl and alkyl groups are successfully converted to the corresponding ketones in good to excellent yields. In addition, the present reaction conditions selectively transform a secondary hydroxy moiety over different classes of hydroxy groups.

Modulation Effect on Tubulin Polymerization, Cytotoxicity and Antioxidant Activity of 1H-Benzimidazole-2-Yl Hydrazones

1H-benzimidazol-2-yl hydrazones with varying hydroxy and methoxy phenyl moieties were designed. Their effect on tubulin polymerization was evaluated in vitro on porcine tubulin. The compounds elongated the nucleation phase and slowed down the tubulin polymerization comparably to nocodazole. The possible binding modes of the hydrazones with tubulin were explored by molecular docking at the colchicine binding site. The anticancer activity was evaluated against human malignant cell lines MCF-7 and AR-230, as well as against normal fibroblast cells 3T3 and CCL-1. The compounds demonstrated a marked antineoplastic activity in low micromolar concentrations in both screened in vitro tumor models. The most active were the trimethoxy substituted derivative 1i and the positional isomers 1j and 1k, containing hydroxy and methoxy substituents: they showed IC50 similar to the reference podophyllotoxin in both tumor cell lines, accompanied with high selectivity towards the malignantly transformed cells. The compounds exerted moderate to high ability to scavenge peroxyl radicals and certain derivatives-1l containing metha-hydroxy and para-methoxy group, and 1b-e with di/trihydroxy phenyl moiety, revealed HORAC values high or comparable to those of well-known phenolic antioxidants. Thus the 1H-benisimidazol-2-yl hydrazones with hydroxy/methoxy phenyl fragments were recognized as new agents exhibiting promising combined antioxidant and antineoplastic action.

Copper-Catalyzed Asymmetric Sulfonylative Desymmetrization of Glycerol.

Glycerol is the main side product in the biodiesel manufacturing process, and the development of glycerol valorization methods would indirectly contribute the sustainable biodiesel production and decarbonization. Transformation of glycerol to optically active C3 units would be one of the attractive routes for glycerol valorization. We herein present the asymmetric sulfonylative desymmetrization of glycerol by using a CuCN/(R,R)-PhBOX catalyst system to provide an optically active monosulfonylated glycerol in high efficiency. A high degree of enantioselectivity was achieved with a commercially available chiral ligand and an inexpensive carbonate base. The optically active monosulfonylated glycerol was successfully transformed into a C3 unit attached with differentially protected three hydroxy moieties. In addition, the synthetic utility of the present reaction was also demonstrated by the transformation of the monosulfonylated glycerol into an optically active synthetic ceramide, sphingolipid E.

Chemo-enzymatic Synthesis of Pseudo-trisaccharide Aminoglycoside Antibiotics with Enhanced Nonsense Read-through Inducer Activity.

Aminoglycosides (AGs) are broad-spectrum antibiotics used to treat bacterial infections. Over the last two decades, studies have reported the potential of AGs in the treatment of genetic disorders caused by nonsense mutations, owing to their ability to induce the ribosomes to read through these mutations and produce a full-length protein. However, the principal limitation in the clinical application of AGs arises from their high toxicity, including nephrotoxicity and ototoxicity. In this study, five novel pseudo-trisaccharide analogs were synthesized by chemo-enzymatic synthesis by acid hydrolysis of commercially available AGs, followed by an enzymatic reaction using recombinant substrate-flexible KanM2 glycosyltransferase. The relationships between their structures and biological activities, including the antibacterial, nephrotoxic, and nonsense readthrough inducer (NRI) activities, were investigated. The absence of 1-N-acylation, 3',4'-dideoxygenation, and post-glycosyl transfer modifications on the third sugar moiety of AGs diminishes their antibacterial activities. The 3',4'-dihydroxy and 6'-hydroxy moieties regulate the in vitro nephrotoxicity of AGs in mammalian cell lines. The 3',4'-dihydroxy and 6'-methyl scaffolds are indispensable for the ex vivo NRI activity of AGs. Based on the alleviated in vitro antibacterial properties and nephrotoxicity, and the highest ex vivo NRI activity among the five compounds, a kanamycin analog (6'-methyl-3''-deamino-3''-hydroxykanamycin C) was selected as a novel AG hit for further studies on human genetic disorders caused by premature transcriptional termination.

Artificial Water Channels—Progress Innovations and Prospects

Artificial Water Channels—Progress Innovations and Prospects

Photodissociation Dynamics of Astrophysically Relevant Propyl Derivatives (C3H7X; X = CN, OH, HCO) at 157 nm Exploiting an Ultracompact Velocity Map Imaging Spectrometer: The (Iso)Propyl Channel.

The photodissociation dynamics of astrophysically relevant propyl derivatives (C3H7X; X = CN, OH, HCO) at 157 nm exploiting an ultracompact velocity map imaging (UVMIS) setup has been reported. The successful operation of UVMIS allowed the exploration of the 157 nm photodissociation of six (iso)propyl systems─n/i-propyl cyanide (C3H7CN), n/i-propyl alcohol (C3H7OH), and (iso)butanal (C3H7CHO)─to explore the C3H7 loss channel. The distinct center-of-mass translational energy distributions for the i-C3H7X (X= CN, OH, HCO) could be explained through preferential excitation of the low frequency C-H bending modes of the formyl moiety compared to the higher frequency stretching of the cyano and hydroxy moieties. Although the ionization energy of the n-C3H7 radical exceeds the energy of a 157 nm photon, C3H7+ was observed in the n-C3H7X (X = CN, OH, HCO) systems as a result of photoionization of vibrationally "hot" n-C3H7 fragments, photoionization of i-C3H7 after a hydrogen shift in vibrationally "hot" n-C3H7 radicals, and/or two-photon ionization. Our experiments reveal that at least the isopropyl radical (i-C3H7) and possibly the normal propyl radical (n-C3H7) should be present in the interstellar medium and hence searched for by radio telescopes.

Robust Mesoporous Functional Hydrogen-Bonded Organic Framework for Hypochlorite Detection.

Although tremendous progress has been achieved in the field of hydrogen-bonded organic frameworks (HOFs), the low stability, small/none pores, and difficult functionality severely obstruct their development. Herein, a novel robust mesoporous HOF (HOF-FAFU-1) decorated with a high density of free hydroxy moieties has been designed and readily synthesized in the de novo synthesis. In HOF-FAFU-1, the planar building blocks are connected to each other by typical intermolecular carboxylate dimers to form two-dimensional (2D) layers with sql topology, which are further connected to their adjacent layers by face-to-face π-π interactions to obtain a three-dimensional (3D) open mesoporous framework. Owing to the high density of intermolecular hydrogen bonding and strong π-π interactions, HOF-FAFU-1 is very stable, allowing it to retain its structure in aqueous solutions with a pH range of 1-9. Benefiting from the decorated hydroxy moieties, HOF-FAFU-1 was exploited as a fluorescent sensor for hypochlorite detection in water media by a turn-off mode, which cannot be realized by its nonhydroxy groups anchoring counterpart (HOF-TCBP). The proposed sensing system is highly efficient, validated by a very broad linear range (0-0.45 mM), fast response (15 s), and small limit of detection (LOD) (1.32 μM). The fluorescent quenching of HOF-FAFU-1 toward hypochlorite was also investigated, mainly being ascribed to the transformation of building blocks from the fluorescent reduced state to the nonfluorescent oxidative state. This work not only demonstrates that HOFs integrated with high stability and large pores as well as high density of functional groups can be simultaneously realized by judicious design of building blocks but also conceptually elucidates that such HOFs can effectively extend the application fields of HOFs.

Photoredox-Catalyzed and Copper(II) Salt-Assisted Radical Addition/Hydroxylation Reaction of Alkenes, Sulfur Ylides, and Water

A visible light-driven photoredox-catalyzed and copper(II)-assisted three-component radical addition/hydroxylation reaction of alkenes, sulfur ylides, and water is reported. This process shows broad substrate scope and high functional group tolerance, with respect to both readily available sulfur ylides and alkenes, providing high-yielding and practical access to valuable γ-hydroxy carbonyl compounds. Key to the success of the reaction is the controlled generation of α-carbonyl carbon radicals from sulfur ylides via sulfonium salts by a visible-light-driven proton-coupled electron transfer (PCET) strategy in a mixture of 2,2,2-trifluoroethanol/CH2Cl2. Addition of Cu(TFA)2·H2O helps to accelerate the radical-cation crossover to improve the reaction efficiency. Mechanistic studies suggest that the hydroxy moiety in the products stems from water. This study also builds up a platform for further investigation into the radical synthetic chemistry of sulfur ylides.