Pyridoxine‐Derived Organoselenium Compounds with Glutathione Peroxidase‐Like and Chain‐Breaking Antioxidant Activity

One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis‐4,5‐(carboethoxy)‐2‐iodo‐3‐pyridinol with disodium diselenide and LiAlH₄‐reduction. After work‐up, selone 7 was isolated in good yield as an air‐stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se ??? H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2 kcal mol^?1. Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12 , and, on further oxidation, seleninic acid 13 . Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14 . The glutathione peroxidase‐like properties of the pyridoxine‐derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain‐breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N‐acetylcysteine as a thiol reducing agent. Diselenide 15 could match α‐tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time.     

Synthesis and Structure–Activity Correlation Studies of Secondary‐ and Tertiary‐Amine‐Based Glutathione Peroxidase Mimics

In this study, a series of secondary‐ and tertiary‐amino‐substituted diaryl diselenides were synthesized and studied for their glutathione peroxidase (GPx) like antioxidant activities with H₂O₂, cumene hydroperoxide, or tBuOOH as substrates and with PhSH or glutathione (GSH) as thiol cosubstrates. This study reveals that replacement of the tert‐amino groups in benzylamine‐based diselenides by sec‐amino moieties drastically enhances the catalytic activities in both the aromatic thiol (PhSH) and GSH assay systems. Particularly, the N‐propyl‐ and N‐isopropylamino‐substituted diselenides are 8–18 times more active than the corresponding N,N‐dipropyl‐ and N,N‐diisopropylamine‐based compounds in all three peroxide systems when GSH is used as the thiol cosubstrate. Although the catalytic mechanism of sec‐amino‐substituted diselenides is similar to that of the tert‐amine‐based compounds, differences in the stability and reactivity of some of the key intermediates account for the differences in the GPx‐like activities. It is observed that the sec‐amino groups are better than the tert‐amino moieties for generating the catalytically active selenols. This is due to the absence of any significant thiol‐exchange reactions in the selenenyl sulfides derived from sec‐amine‐based diselenides. Furthermore, the seleninic acids (RSeO₂H) derived from the sec‐amine‐based compounds are more stable toward further reactions with peroxides than their tert‐amine‐based analogues.     

Thermosensitive and control release behavior of poly (N‐isopropylacrylamide‐co‐acrylic acid) latex particles

In this work, poly(N‐isopropylacrylamide‐co‐acrylic acid) (poly(NIPAAm‐AA)) copolymer latex particles (microgels) were synthesized by the method of soapless emulsion polymerization. Poly(NIPAAm‐AA) copolymer microgels have the property of being thermosensitive. The concentration of acrylic acid (AA) and crosslinking agent N,N′‐methylenebisacrylamide were important factors to influence the lower critical solution temperature (LCST) of poly(NIPAAm‐AA) microgels. The effects of AA and crosslinking agent on the swelling behavior of poly(NIPAAm‐AA) microgels were also studied. The poly(NIPAAm‐AA) copolymer microgels were then used as a thermosensitive drug carrier to load caffeine. The effects of concentration of AA and crosslinking agent on the control release of caffeine were investigated. How the AA content and crosslinking agent influenced the morphology and LCST of the microgels was discussed in detail. The relationship of morphology, swelling, and control release behavior of these thermosensitive microgels was established. A new scheme was proposed to interpret the control release of the microgels with different morphological structures. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5734–5741, 2008     

Dual stimuli‐responsive microgels based on photolabile crosslinker: Temperature sensitivity and light‐induced degradation

The synthesis and characterization of a new photocleavable crosslinker is presented here. Dual stimuli‐responsive P(VCL‐co‐NHMA) microgels were prepared by precipitation polymerization of vinylcaprolactam (VCL) with N‐hydroxymethyl acrylamide (NHMA) and the new crosslinker. The microgels had distinct temperature sensitivity as observed in the case of PVCL‐based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing NHMA content. Photolytic degradation experiments were investigated by irradiation with UV light, which led to microgel disintegration caused by cleavage of the photolabile crosslinking points. The degradation behavior of the microgels was conducted with respect to degradation rates by means of the relative turbidity changes. Hence, the microgels could totally degrade into short linear polymers by UV light, thus representing a great potential as new light and temperature dual responsive nanoscale materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1676–1685     

Polypyrrole/poly(N‐isopropylacrylamide‐co‐acrylic acid) thermosensitive and electrically conductive composite microgels

The electrically conductive polypyrrole/dodecylbenzene sulfonic acid/poly(N‐isopropylacrylamide‐co‐acrylic acid) (PPy/DBSA/poly(NIPAAm‐co‐AA)) composite microgels were synthesized by a chemical oxidation of pyrrole in the presence of DBSA as the primary dopant, and poly(NIPAAm‐co‐AA) microgels as the polymeric codopant and template, in which APS was used as the oxidant. It was proposed to prepare “intelligent” polymer microgel particles containing both thermosensitive and electrically conducting properties. The polymerization of pyrrole took place directly inside the microgel networks, leading to formation of composite microgels and the morphology was observed by transmission electron microscope. PPy particles interacted strongly with microgels, as the acid groups of microgels acted as the polymeric codopant. The composite microgels thus formed showed electrically conducting behavior dependent on humidity and temperature. At temperatures lower than lower critical solution temperature, the conductivity decreased with increasing the humidity and a small hysteresis phenomenon was observed. The hysteresis became indistinct when temperature was near volume phase transition temperature. However, after the treatment of high temperature and high humidity, the conductivity increased surprisingly due to the structure reorganization inside the composite microgels. The distinctive functionality of the PPy composite microgels was expected to be utilized in many attractive applications. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1648–1659, 2006     

Investigation of the Catalytic Activity of a 2‐Phenylidenepyridine Palladium(II) Complex Bearing 4,5‐Dicyano‐1,3‐bis(mesityl)imidazol‐2‐ylidene in the Mizoroki‐Heck Reaction

The phenylidenepyridine (ppy) palladacycles [PdCl(ppy)(IMes)] ( 4 ) [IMes = 1,3‐bis(mesityl)imidazol‐2‐ylidene] and [PdCl(ppy){(CN)₂IMes}] ( 6 ) [(CN)₂IMes = 4,5‐dicyano‐1,3‐bis(mesityl)imidazol‐2‐ylidene] were prepared by facile two step syntheses, starting with the reaction of palladium(II) chloride with 2‐phenylpyridine followed by subsequent addition of the NHC ligand to the precatalyst precursor [PdCl(ppy)]₂. Suitable crystals for the X‐ray analysis of the complexes 4 and 6 were obtained. It was shown that 6 has a shorter NHC‐palladium bond than the IMes complex 4 . The difference of the palladium carbene bond lengths based on the higher π‐acceptor strength of (CN)₂IMes in comparison to IMes. Thus, (CN)₂IMes should stabilize the catalytically active central palladium atom better than IMes. As a measure for the π‐acceptor strength of (CN)₂IMes compared to IMes, the selone (CN)₂IMes · Se ( 7 ) was prepared and characterized by ⁷⁷Se‐NMR spectroscopy. The π‐acceptor strength of 7 was illuminated by the shift of its ⁷⁷Se‐NMR signal. The ⁷⁷Se‐NMR signal of 7 was shifted to much higher frequencies than the ⁷⁷Se‐NMR signal of IMes · Se. Catalytic experiments using the Mizoroki‐Heck reaction of aryl chlorides with n‐butyl acrylate showed that 6 is the superior performer in comparison to 4 . Using complex 6 , an extensive substrate screening of 26 different aryl bromides with n‐butyl acrylate was performed. Complex 6 is a suitable precatalyst for para‐substituted aryl bromides. The catalytically active species was identified by mercury poisoning experiments to be palladium nanoparticles.     

Preparation of P(MBA‐co‐MAA)/Zr(OH)4/P(EGDMA‐co‐MAA)/TiO2 Tetra‐layer Hybrid Microspheres and the Corresponding ZrO2/TiO2 Double‐shelled Hollow Microspheres

Double‐shelled zirconia/titania (ZrO₂/TiO₂) hollow microspheres were prepared by the selective removal of the polymer components via the calcination of the corresponding tetra‐layer poly(N,N′‐methylenebisacryl amide‐co‐methacrylic acid) (P(MBA‐co‐MAA))/Zr(OH)₄/poly(ethyleneglycol dimethacrylate‐co‐methacrylic acid) (P(EGDMA‐co‐MAA))/TiO₂ hybrid microspheres. These tetra‐layer microspheres were synthesized by the combination of the distillation copolymerization of N,N(‐methylenebisacryl amide‐co‐methacrylic acid (MBA) or ethyleneglycol dimethacrylate (EGDMA) crosslinker and methacrylic acid (MAA) for the preparation of polymer core and third‐layer as well as the controlled sol‐gel hydrolysis of inorganic precursors for the construction of zirconium hydroxide (Zr(OH)₄) and titania (TiO₂) layers. The thicknesses of zirconia and titania shell‐layers were conveniently controlled via varying the feed of zirconium n‐butoxide (Zr(OBu)₄) and titanium tetrabutoxide (TBOT) during the sol‐gel hydrolysis, while the sizes of polymer layers were tuned through a multi‐stage distillation precipitation copolymerization. The structure and morphology of the resultant microspheres were characterized by transmission electron microscopy (TEM), X‐ray diffractometer (XRD), X‐ray photoelectronic spectroscopy (XPS), and thermogrametric analysis (TGA).     

Oxidation‐Triggered Ring‐Opening Metathesis Polymerization

Eight new N‐Hoveyda‐type complexes were synthesized in yields of 67–92 % through reaction of [RuCl₂(NHC)(Ind)(py)] (NHC=1,3‐bis(2,4,6‐trimethylphenylimidazolin)‐2‐ylidene (SIMes) or 1,3‐bis(2,6‐diisopropylphenylimidazolin)‐2‐ylidene (SIPr), Ind=3‐phenylindenylid‐1‐ene, py=pyridine) with various 1‐ or 1,2‐substituted ferrocene compounds with vinyl and amine or imine substituents. The redox potentials of the respective complexes were determined; in all complexes an iron‐centered oxidation reaction occurs at potentials close to E=+0.5 V. The crystal structures of the reduced and of the respective oxidized Hoveyda‐type complexes were determined and show that the oxidation of the ferrocene unit has little effect on the ruthenium environment. Two of the eight new complexes were found to be switchable catalysts, in that the reduced form is inactive in the ring‐opening metathesis polymerization of cis‐cyclooctene (COE), whereas the oxidized complexes produce polyCOE. The other complexes are not switchable catalysts and are either inactive or active in both reduced and oxidized states.     

N‐vinylcaprolactam‐based microgels: Synthesis and characterization

Poly(N‐vinylcaprolactam) (PVCL) is well known for its thermoresponsive behavior in aqueous solutions. PVCL combines useful and important properties; it is biocompatible polymer with the phase transition in the region of physiological temperature (32–38 °C). This combination of properties allows consideration of PVCL as a material for design biomedical devices and use in drug delivery systems. In this work, PVCL based temperature‐sensitive crosslinked particles (microgels) were synthesized in a batch reactor to analyze the effect of the crosslinker, initiator, surfactant, temperature, and VCL concentration on polymerization process and final microgels characteristics. The mean particle diameters at different temperatures and the volume phase‐transition temperature of the final product were analyzed. To obtain information about the inner structure of microgel particles, semicontinuous polymerizations were carried out and the evolution of the hydrodynamic average particle diameters at different temperatures of the microgel synthesized was investigated. In the case of microgel particles obtained in a batch reactor the size and the swelling‐de‐swelling behavior as a function of the temperature of the medium can be tuned by modulating the reaction variables. When the microgel particles were synthesized in a semibatch reactor different swelling‐de‐swelling behaviors were observed depending on particles inner structure. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2510–2524, 2008     

Synthesis and structure of a µ‐oxo diiron(III) complex with an N‐pyridylmethyl‐N,N‐bis(4‐methylbenzimidazol‐2‐yl)amine ligand and its catalytic property for hydrocarbon oxidation

A µ‐oxo diiron(III) complex [{Fe(pbba)Cl}₂(µ‐O)]Cl₂ (1, pbba = N‐pyridylmethyl‐N,N‐bis(4‐methylbenzimidazol‐2‐yl)amine) bearing multi‐imidazolyl motifs was synthesized and characterized by X‐ray crystallography to closely mimic the structural features of methane monooxygenase. As shown by its X‐ray crystal structure, complex 1 is a centrosymmetric dimer with an Fe? O? Fe angle of 180° , and pseudo‐octahedral around each iron(III) center. The catalytic ability of title compound in the oxidation of alkane and alkene is investigated by employing tert‐butylhydroperoxide and m‐chloroperbenzoic acid as oxidants under mild conditions. The catalytic oxidation results showed that radical intermediate dominates the oxidation process. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis strategies to incorporate acrylic acid into N‐vinylcaprolactam‐based microgels

Two different synthesis strategies were used to synthesize N‐vinylcaprolactam (VCL)‐acrylic acid (AA)‐based temperature‐ and pH‐sensitive microgels under the adequate conditions to avoid possible hydrolysis of VCL due to the presence of carboxylic groups provided by AA. Polymeric and colloidal features of the microgels were analyzed: the partial conversion evolutions of each comonomer were determined by ¹H NMR and the swelling/deswelling behavior by means of Photon Correlation Spectroscopy. Considering that microgels are porous soft nanoparticles, conductimetric titrations at the swollen state were carried out to calculate the volumetric charge density. The results indicate that the addition of AA after 30 minutes of reaction time helped to incorporate higher amounts of AA into microgels and as a result, to obtain both temperature‐ and pH‐sensitive nanoparticles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Catalytic reduction of 4‐nitrophenol using silver nanoparticles‐engineered poly(N‐isopropylacrylamide‐co‐acrylamide) hybrid microgels

Nearly monodisperse poly(N ‐isopropylacrylamide‐co ‐acrylamide) [P(NIPAM‐co‐AAm)] microgels were synthesized using precipitation polymerization in aqueous medium. These microgels were used as microreactors to fabricate silver nanoparticles by chemical reduction of silver ions inside the polymer network. The pure and hybrid microgels were characterized using Fourier transform infrared and UV–visible spectroscopies, dynamic light scattering, X‐ray diffraction, thermogravimetric analysis, differential scanning calorimetry and transmission electron microscopy. Results revealed that spherical silver nanoparticles having diameter of 10–20 nm were successfully fabricated in the poly(N ‐isopropylacrylamide‐co ‐acrylamide) microgels with hydrodynamic diameter of 250 ± 50 nm. The uniformly loaded silver nanoparticles were found to be stable for long time due to donor–acceptor interaction between amide groups of polymer network and silver nanoparticles. Catalytic activity of the hybrid system was tested by choosing the catalytic reduction of 4‐nitrophenol as a model reaction under various conditions of catalyst dose and concentration of NaBH₄ at room temperature in aqueous medium to explore the catalytic process. The progress of the reaction was monitored using UV–visible spectrophotometry. The pseudo first‐order kinetic model was employed to evaluate the apparent rate constant of the reaction. It was found that the apparent rate constant increased with increasing catalyst dose due to an increase of surface area as a result of an increase in the number of nanoparticles.     

Bis(N,N‐diethyl‐1,1‐di­seleno­carbam­ato‐Se)­selenium, [(Se2CNEt2)2Se]

The poly­seleno title compound, bis(N,N‐diethyl­seleno­carbamoyl) tri­selenide, [(Se₂CNEt₂)₂Se] or C₁₀H₂₀N₂Se₅, is obtained from the disproportion of sodium N,N‐diethyl‐1,1‐di­seleno­carbamate. An Se atom connects two N,N‐diethyl‐1,1‐di­seleno­carbamate groups with Se—Se distances in the range 2.4500 (11)–2.8601 (12) Å     

Multi‐responsive methylcellulose/Fe‐alginate‐g‐PVA/PVA/Fe3O4 microgels for immobilizing enzyme

To take advantage of the respective character of methylcellulose (MC), poly(vinyl alcohol) (PVA), and alginate, novel physically cross‐linked methylcellulose/Fe‐alginate‐g‐PVA/PVA (MC/Fe‐Alg‐g‐PVA/PVA) microgels were prepared by emulsification/thermal gelation/freezing–thawing/ionic cross‐linking technique. Subsequently, some ferrous ions bound in the microgels were transformed into magnetite via in situ self oxidation. A model enzyme α‐amylase was immobilized into microgels by direct adsorption. The release behavior of α‐amylase indicated that the obtained complex microgels were magnetic‐, temperature‐, and pH‐ triple sensitive. Copyright © 2010 John Wiley & Sons, Ltd.     

TMEDA in Iron‐Catalyzed Hydromagnesiation: Formation of Iron(II)‐Alkyl Species for Controlled Reduction to Alkene‐Stabilized Iron(0)

N,N,N′,N′‐Tetramethylethylenediamine (TMEDA) has been one of the most prevalent and successful additives used in iron catalysis, finding application in reactions as diverse as cross‐coupling, C?H activation, and borylation. However, the role that TMEDA plays in these reactions remains largely undefined. Herein, studying the iron‐catalyzed hydromagnesiation of styrene derivatives using TMEDA has provided molecular‐level insight into the role of TMEDA in achieving effective catalysis. The key is the initial formation of TMEDA–iron(II)–alkyl species which undergo a controlled reduction to selectively form catalytically active styrene‐stabilized iron(0)–alkyl complexes. While TMEDA is not bound to the catalytically active species, these active iron(0) complexes cannot be accessed in the absence of TMEDA. This mode of action, allowing for controlled reduction and access to iron(0) species, represents a new paradigm for the role of this important reaction additive in iron catalysis.     

Syntheses,Structures, and Catalytic Activities of Copper(I) Complexes with the Ligand 2(4,5‐Diphenyl‐1H‐imidazol‐2‐yl)­pyridine

Two copper(I) complexes of compositions [Cu(HL)I]₂ · EtOH ( 1 ) and [Cu(HL)₃]I · MeOH ( 2 ) were synthesized via the reactions of HL [HL = 2(4,5‐diphenyl‐1H‐imidazol‐2‐yl)pyridine] and CuI in EtOH and MeOH, respectively, under solvothermal conditions. The complexes were characterized by X‐ray single crystal diffraction, IR spectroscopy, and elemental analysis. Compounds 1 and 2 are catalytically active towards ketalization reaction, giving various ketals under mild conditions.     

Probing the Formation of a Seleninic Acid in Living Cells by the Fluorescence Switching of a Glutathione Peroxidase Mimetic

Glutathione peroxidase (GPx) is a selenoenzyme that protects cells against oxidative damage. Although the formation of a seleninic acid (‐SeO₂H) by this enzyme during oxidative stress has been proposed, a selenic acid has not been identified in cells. Herein, we report that the formation of a seleninic acid can be monitored in living cells by using a redox‐active ebselen analogue with a naphthalimide fluorophore. The probe reacts with H₂O₂ to generate the highly fluorescent seleninic acid. The electron withdrawing nature of the ‐SeO₂H moiety and strong Se???O interactions, which prevent the photoinduced electron transfer, are responsible for the fluorescence.     

meso–meso‐Linked Diarylamine‐Fused Porphyrin Dimers

A meso–meso‐linked diphenylamine‐fused porphyrin dimer and its methoxy‐substituted analogue were synthesized from a meso–meso‐linked porphyrin dimer by a reaction sequence involving Ir‐catalyzed β‐selective borylation, iodination, meso‐chlorination, and S_NAr reactions with diarylamines followed by electron‐transfer‐mediated intramolecular double C?H/C?I coupling. While these dimers commonly display characteristic split Soret bands and small oxidation potentials, they produced different products upon oxidation with tris(4‐bromophenyl)aminium hexachloroantimonate. Namely, the diphenylamine‐fused porphyrin dimer was converted into a dicationic closed‐shell quinonoidal dimer, while the methoxy‐substituted dimer gave a meso–meso, β‐β doubly linked porphyrin dimer.     

Intra‐ and intermolecular Se...X (X = Se,O) interactions in selenium‐containing heterocycles: 3‐benzoylimino‐5‐(morpholin‐4‐yl)‐1,2,4‐diselenazole

In the selenium‐containing heterocyclic title compound {systematic name: N‐[5‐(morpholin‐4‐yl)‐3H‐1,2,4‐diselenazol‐3‐ylidene]benzamide}, C₁₃H₁₃N₃O₂Se₂, the five‐membered 1,2,4‐diselenazole ring and the amide group form a planar unit, but the phenyl ring plane is twisted by 22.12 (19)° relative to this plane. The five consecutive N—C bond lengths are all of similar lengths [1.316 (6)–1.358 (6) Å], indicating substantial delocalization along these bonds. The Se...O distance of 2.302 (3) Å, combined with a longer than usual amide C=O bond of 2.252 (5) Å, suggest a significant interaction between the amide O atom and its adjacent Se atom. An analysis of related structures containing an Se—Se...X unit (X = Se, S, O) shows a strong correlation between the Se—Se bond length and the strength of the Se...X interaction. When X = O, the strength of the Se...O interaction also correlates with the carbonyl C=O bond length. Weak intermolecular Se...Se, Se...O, C—H...O, C—H...π and π–π interactions each serve to link the molecules into ribbons or chains, with the C—H...O motif being a double helix, while the combination of all interactions generates the overall three‐dimensional supramolecular framework.     

Solvent‐ and Temperature‐Controlled In Situ Ligand Reactions Mediated by CuII and 3′‐[(E)‐{[(1S,2S)‐2‐Aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐4‐biphenylcarboxlic Acid

Three new compounds, CuL, CuL′, and Cu₂O₂L′′₂ (H₂L=3′‐[(E)‐{[(1S,2S)‐2‐aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐4‐biphenylcarboxlic acid, H₂L′=3′‐[(E)‐{[(1S,2S)‐2‐aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐5′‐nitro‐4‐biphenylcarboxlic acid, H₂L′′=3′‐(N,N‐dimethylamino methyl)‐4′‐hydroxy‐4‐biphenylcarboxlic acid), were selectively synthesized through a controlled in situ ligand reaction system mediated by copper(II) nitrate and H₂L. Selective nitration was achieved by using different solvent mixtures under relatively mild conditions, and an interesting and economical reductive amination system in DMF/EtOH/H₂O was also found. All crystal structures were determined by single‐crystal X‐ray diffraction analysis. Both CuL and CuL′ display chiral 1D chain structures, whereas Cu₂O₂L′′₂ possesses a structure with 13×16 Å channels and a free volume of 41.4 %. The possible mechanisms involved in this in situ ligand‐controlled reaction system are discussed in detail.