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.     

Synthesis and Characterization of New Cross‐like Porphyrin–Naphthalocyanine and Porphyrin–Phthalocyanine Pentads

Synthesis and characterization of new cross‐like porphyrin–naphthalocyanine and porphyrin–phthalocyanine systems, where one naphthalocyanine and one phthalocyanine are the central moieties of the pentads, respectively, and in both cases substituted with four porphyrin units, in a cross‐shape structure. Porphyrin–naphthalonitrile and porphyrin–phthalonitrile adducts were prepared from the reaction of 5‐(p‐hydroxyphenyl)‐10,15,20‐triphenylporphyrin with the appropriate dihalogenated naphthalonitrile or phthalonitrile, respectively, to provide a straightforward cyclotetramerization in the presence of metallic magnesium, used as template. Spectroscopic characterization and initial photophysical assessment are also reported.     

Synthesis of fused pyrimidines with N‐, S‐heterocyclic moieties by double‐annelation reaction

A variety of tri‐ and tetracyclic hetero systems were obtained by reaction of heteroaromatic ortho‐aminoesters or ortho‐aminonitriles with iminothioether, yielding double‐annelation of a thiazolo[3,2‐a]‐pyrimidine, pyrimido[2,l‐b]thiazine, imidazo[1,2‐a]pyrimidine, and pyrimido[1,2‐a]pyrimidine moieties in a one‐pot process.     

2‐Ethyl­phenyl acridine‐9‐carboxyl­ate and 2,5‐dimethyl­phenyl acridine‐9‐carboxyl­ate

The title compounds, 2‐ethyl­phenyl acridine‐9‐carboxyl­ate, C₂₂H₁₇NO₂, (I), and 2,5‐dimethyl­phenyl acridine‐9‐carboxyl­ate, C₂₂H₁₇NO₂, (II), form triclinic and monoclinic crystals, respectively. Related by a centre of symmetry, adjacent molecules of (I) are linked in the lattice via a network of C—H·π and non‐specific dispersive interactions. As a result, acridine moieties and independent phenyl moieties of (I) are parallel in the lattice. The molecules of (II), arranged in a `head‐to‐tail' manner and related by a centre of symmetry, form pairs stabilized via C—H·π interactions. These are linked in the crystal via dispersive interactions. Acridine and independent phenyl moieties lie parallel within the pairs, while adjacent pairs are perpendicular, forming a herring‐bone pattern.     

Photo‐initiated thiol–ene “click” hydrogels from RAFT‐synthesized poly(N‐isopropylacrylamide)

Despite the efficiency and robustness of the widely used copper‐catalyzed 1,3‐dipolar cycloaddition reaction, the use of copper as a catalyst is often not attractive, particularly for materials intended for biological systems. The use of photo‐initiated thiol‐ene as an alternative “click” reaction to synthesize “model networks” is investigated here. Poly(N‐isopropylacrylamide) precursors were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization and were designed to have trithiocarbonate moieties as end groups. This structure design provides opportunity for subsequent end‐group modifications in preparation for thiol‐ene “click.” Two reaction routes have been proposed and studied to yield thiol and ene moieties. The advantages and disadvantages of each reaction path were investigated to propose a simple but efficient route to prepare copper‐free “click” hydrogels. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4626–4636     

A Palladium(II)‐Catalyzed C?H Activation Cascade Sequence for Polyheterocycle Formation

Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)‐catalyzed C H activation strategy for the construction of such systems has been developed. Starting from simple 1,3‐dienyl‐substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step.     

Zeolitic Imidazolate Framework (ZIF)‐Derived,Hollow‐Core,Nitrogen‐Doped Carbon Nanostructures for Oxygen‐Reduction Reactions in PEFCs

The facile synthesis of a porous carbon material that is doped with iron‐coordinated nitrogen active sites (FeNC‐70) is demonstrated by following an inexpensive synthetic pathway with a zeolitic imidazolate framework (ZIF‐70) as a template. To emphasize the possibility of tuning the porosity and surface area of the resulting carbon materials based on the structure of the parent ZIF, two other ZIFs, that is, ZIF‐68 and ZIF‐69, are also synthesized. The resulting active carbon material that is derived from ZIF‐70, that is, FeNC‐70, exhibits the highest BET surface area of 262 m² g^?1 compared to the active carbon materials that are derived from ZIF‐68 and ZIF‐69. The HR‐TEM images of FeNC‐70 show that the carbon particles have a bimodal structure that is composed of a spherical macroscopic pore (about 200 nm) and a mesoporous shell. X‐ray photoelectron spectroscopy (XPS) reveals the presence of Fe‐N‐C moieties, which are the primary active sites for the oxygen‐reduction reaction (ORR). Quantitative estimation by using EDAX analysis reveals a nitrogen content of 14.5 wt. %, along with trace amounts of iron (0.1 wt. %), in the active FeNC‐70 catalyst. This active porous carbon material, which is enriched with Fe‐N‐C moieties, reduces the oxygen molecule with an onset potential at 0.80 V versus NHE through a pathway that involves 3.3–3.8 e^? under acidic conditions, which is much closer to the favored 4 e^? pathway for the ORR. The onset potential of FeNC‐70 is significantly higher than those of its counterparts (FeNC‐68 and FeNC‐69) and of other reported systems. The FeNC‐based systems also exhibit much‐higher tolerance towards MeOH oxidation and electrochemical stability during an accelerated durability test (ADT). Electrochemical analysis and structural characterizations predict that the active sites for the ORR are most likely to be the in situ generated N? FeN₂₊₂/C moieties, which are distributed along the carbon framework.     

A diaryl‐terminated hexa‐1,5‐diyne‐3,4‐dione

The structure of bis­(4‐tert‐butyl‐2,6‐dimethyl­phenyl)hexa‐1,5‐diyne‐3,4‐dione, C₃₀H₃₄O₂, has been determined, revealing an extended s‐trans conformation of the dione and the two ynone moieties, which are shielded by the flanking methyl substituents. The structural parameters and the packing arrangement suggest little electronic delocalization between the two ynone moieties.     

Formation of thermo‐sensitive and cross‐linkable micelles by self‐assembly of poly(pentafluorophenyl acrylate)‐containing block copolymer

Poly(pentafluorophenyl acrylate)‐block‐poly(N‐isopropylacrylamide) (PPFPA‐b‐PNIPAM) is synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. Light‐responsive moieties of ortho‐nitrobenzyl (ONB)‐protected diamine are partially introduced to the PFPA moieties via postpolymerization modification. The amphiphilic block copolymers are assembled into micelles in water. The ONB‐protected diamine group in the micelle core is released upon UV irradiation, which subsequently induces an in situ cross‐linking by a spontaneous reaction with the remaining PFPA groups in the core and yields stable cross‐linked micelles. Micellization of the copolymers is confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). 4‐Nitro‐7‐piperazino‐2,1,3‐benzoxadiazole (NBD) and pyrene are loaded in the core of cross‐linked micelles to demonstrate the possibility for additional post‐functionalization of residual PFPA moieties and hydrophobic molecule encapsulation, respectively. It is anticipated that these micelles can be alternative cargos for incorporating active compounds that may be useful for advanced applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1103–1113     

Precision synthesis of microstructures in star‐shaped copolymers of ϵ‐caprolactone,L‐lactide,and 1,5‐dioxepan‐2‐one

Star‐shaped homo‐ and copolymers were synthesized in a controlled fashion using two different initiating systems. Homopolymers of ε‐caprolactone, L ‐lactide, and 1,5‐dioxepan‐2‐one were firstly polymerized using (I) a spirocyclic tin initiator and (II) stannous octoate (cocatalyst) together with pentaerythritol ethoxylate 15/4 EO/OH (coinitiator), to give polymers with identical core moieties. Our gained understanding of the versatile and controllable initiator systems kinetics, the transesterification reactions occurring, and the role which the reaction conditions play on the material outcome, made it possible to tailor the copolymer microstructure. Two strategies were used to successfully synthesize copolymers of different microstructures with the two initiator systems, i.e., a more multiblock‐ or a block‐structure. The correct choice of the monomer addition order enabled two distinct blocks to be created for the copolymers of poly(DXO‐co‐LLA) and poly(CL‐co‐LLA). In the case of poly(CL‐co‐DXO), multiblock copolymers were created using both systems whereas longer blocks were created with the spirocyclic tin initiator. © 2008 Wiley Periodicals, Inc. JPolym Sci Part A: Polym Chem 46: 1249–1264, 2008     

Pericyclic Transformations at the Periphery of Chromen‐4‐one (=4H‐1‐Benzopyran‐4‐one): An Unusual Preference for a 1,5‐Shift of Allylic Moieties over the Ene Reaction

Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems, similarly disposed moieties on the periphery of the chromen‐4‐one (=4H‐1‐benzopyran‐4‐one) system fail to undergo an ene reaction and display a rather unusual preference for an overall [1,5] shift of the allylic C‐atom. Thus, heating xylene solutions of 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, and 2‐(N‐cinnamylamino)‐substituted (E)‐(oxochromenyl)propenoates 9a – c and 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted (E)‐(oxochromenyl)propenoates 16a – c in a sealed tube at 220–230° leads to a [1,5] shift of the allylic moieties (allyl, crotyl, cinnamyl), which is followed by intramolecular cyclization involving the N‐atom and the ester function, to give the 3‐allyl‐3‐crotyl‐, and 3‐cinnamyl‐substituted‐1‐phenyl‐ or 1‐benzyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 10a – c and 17a – c . The anticipated carbonyl–ene reaction in the 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, 2‐(N‐cinnamylanilino)‐, 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted 4‐oxochromene‐3‐carboxaldehydes 8a – c and 15a – c is also not observed, and these molecules remain untransformed under identical conditions. No [1,5] shifts of benzyl, phenyl, or methyl groups are observed, even in the absence of allylic moieties, though facile [1,5]‐H shift occurs in 2‐(benzylamino)‐ and 2‐(phenylamino)‐substituted (E)‐(oxochromenyl)propenoates 23a , b , which is followed by a similar intramolecular cyclization leading to the 2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 24a , b .     

Columnar Self‐Assembly in Electron‐Deficient Heterotriangulenes

A series of soluble carbonyl‐bridged heterotriangulenes, in which flexible n‐dodecyl chains are attached through different spacers to the planar nitrogen‐centered polycyclic core, have been synthesized. The introduction of triisopropylsilylethynyl moieties enabled, for the first time, the characterization of single‐crystal columnar packing of a substituted heterotriangulene by X‐ray crystallography. Electrochemical studies disclosed the carbonyl‐bridged heterotriangulene core as a reasonably strong acceptor for a reversible two‐electron transfer. The tendency of substituted heterotriangulenes to self‐assemble in solution, on surfaces, and in the bulk appeared to sensitively depend on the nature of the lateral substituents, their steric demand, and the applied solution processing conditions. It can be concluded that 1) additional phenylene moieties between the heterotriangulene core and the n‐dodecyl chains facilitate self‐assembly by extending the π‐conjugated polycyclic disc, 2) the rod‐like ethynylene spacers introduce some additional flexibility and hence lower the overall aggregation tendency, and 3) the combination of both features in the phenylene–ethynylene moieties induces thermotropic liquid crystallinity.     

[2]Pseudorotaxanes Based on Naphtho‐21‐crown‐7 and Secondary Dialkylammonium Salts: Remarkably Improved Association Constants Among Four Threaded Structures

This research article is focused on the recognition interaction of a new host naphtho‐21‐crown‐7 and four secondary dialkylammonium salts. In acetone, they can form 1:1 host‐guest complexes which belong to slow‐exchange systems. We also found the differences of binding affinity and binding selectivity between the host and its complementary guest moieties, which could be ascribed to the aromatic π‐π stacking effect and the acidity increase of N‐methylene and ammonium hydrogens due to the increasing electron withdrawing ability from butyl to methoxyphenyl to phenyl to p‐cyanophenyl substituents in the recognition motif.     

Cross‐Coupling of Aryl‐Bromide and Porphyrin‐Bromide on an Au(111) Surface

Cross‐coupling is of great importance in organic synthesis. Here it is demonstrated that cross‐coupling of aryl‐bromide and porphyrin‐bromide takes place on a Au(111) surface in vacuo. The products are oligomers consisting of porphyrin moieties linked by p‐phenylene at porphyrin’s meso‐positions. The ratio of the cross‐coupled versus homocoupled bonds can be regulated by the reactant concentrations. Kinetic Monte Carlo simulations were applied to determine the activation barrier. It is expected that this reaction can be employed in other aryl‐bromide precursors for designing alternating co‐polymers incorporating porphyrin and other functional moieties.     

Protecting‐Group‐Controlled Enzymatic Glycosylation of Oligo‐N‐Acetyllactosamine Derivatives

We describe a chemoenzymatic strategy that can give a library of differentially fucosylated and sialylated oligosaccharides starting from a single chemically synthesized tri‐N‐acetyllactosamine derivative. The common precursor could easily be converted into 6 different hexasaccharides in which the glucosamine moieties are either acetylated (GlcNAc) or modified as a free amine (GlcNH₂) or Boc (GlcNHBoc). Fucosylation of the resulting compounds by a recombinant fucosyl transferase resulted in only modification of the natural GlcNAc moieties, providing access to 6 selectively mono‐ and bis‐fucosylated oligosaccharides. Conversion of the GlcNH₂ or GlcNHBoc moieties into the natural GlcNAc, followed by sialylation by sialyl transferases gave 12 differently fucosylated and sialylated compounds. The oligosaccharides were printed as a microarray that was probed by several glycan‐binding proteins, demonstrating that complex patterns of fucosylation can modulate glycan recognition.     

Chemical cross‐linking with a diazirine photoactivatable cross‐linker investigated by MALDI‐ and ESI‐MS/MS

Crystallography and nuclear magnetic resonance are well‐established methods to study protein tertiary structure and interactions. Despite their usefulness, such methods are not applicable to many protein systems. Chemical cross‐linking of proteins coupled with mass spectrometry allows low‐resolution characterization of proteins and protein complexes based on measuring distance constraints from cross‐links. In this work, we have investigated cross‐linking by means of a heterobifunctional cross‐linker containing a traditional N‐hydroxysuccinimide (NHS) ester and a UV photoactivatable diazirine group. Activation of the diazirine group yields a highly reactive carbene species, with potential to increase the number of cross‐links compared with homobifunctional, NHS‐based cross‐linkers. Cross‐linking reactions were performed on model systems such as synthetic peptides and equine myoglobin. After reduction of the disulfide bond, the formation of intra‐ and intermolecular cross‐links was identified and the peptides modified with both NHS and diazirine moieties characterized. Fragmentation of these modified peptides reveals the presence of a marker ion for intramolecular cross‐links, which facilitates identification. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthese von Sulfolenobilinen und deren Cyclisierung zu Chlorinatozink‐Fulleren‐Dyaden

Synthesis of Sulfolenobilins and Their Cyclization Directed to Chlorinatozinc‐Fullerene Dyads A novel chlorinatozinc‐fullerene dyad 18 was synthesized to model the photosynthetic reaction center. The synthetic key step for the formation of the dyad 18 is an unusual one‐pot reaction of the (sulfolenobilinato)nickel rac‐ 16a , b with concomitant generation of the chlorin macrocycle and linkage to the [5,6]fullerene‐C₆₀‐I_h. This one‐pot reaction is a complex cascade of single reaction steps with a total yield of 32% and an average yield of 83% for the individual steps. The chlorinatozinc‐fullerene dyad is so far one of three examples that contain chlorin moieties, the chromophores in naturally occurring photosynthetic systems.     

Crystal Structure,Magnetic Exchange Interaction,and DFT Study of 2,2′‐(1‐Oxidopyridine‐2,6‐diyl)bis[4,5‐dihydro‐4,4,5,5‐tetramethyl‐3‐oxido‐1H‐imidazol‐1‐oxyl] Hydrate

The structure of a novel oxido‐aminoxyl (=`nitronyl nitroxide') biradical, 2,2′‐(1‐oxidopyridine‐2,6‐diyl)bis[4,5‐dihydro‐4,4,5,5‐tetramethyl‐3‐oxido‐1H‐imidazol‐1‐oxyl] hydrate ( 1 ⋅H₂O) was established by X‐ray analysis in the solid state: monoclinic, space group P2₁/c, Z=4 with a=12.621(4), b=15.704(5), and c=13.001(4) Å, and β=115.202(6)°. Variable‐temperature magnetic susceptibilities show a weak antiferromagnetic interaction between the two oxido‐substituted aminoxyl moieties of 1 , indicative of a singlet ground state. AM1 Calculations located minima for the possible structure based on the X‐ray crystal structure. A hybride density‐functional‐theory calculation with the UB3LYP method from the X‐ray crystal structure establishes the same spin sign in the two aminoxyl moieties and shows that a small spin density is localized at the C‐atoms of the pyridine moiety. These theoretic results are in good agreement with the determined weak antiferromagnetic interaction of 1 .     

D3h‐Symmetric Porphyrin‐Based Rigid Macrocyclic Ligands for Multicofacial Multinuclear Complexes in a One‐Nanometer‐Sized Cavity

The one‐step synthesis of D_3h‐symmetric cyclic porphyrin trimers 1 composed of three 2,2′‐[4,4′‐bis(methoxycarbonyl)]bipyridyl moieties and three porphyrinatozinc moieties was achieved from a nickel‐mediated reductive coupling of meso‐5,15‐bis(6‐chloro‐4‐methoxycarbonylpyrid‐2‐yl)porphyrinatozinc. Although cyclic trimers 1 were obtained as a mixture that included other cyclic and acyclic porphyrin oligomers, an extremely specific separation was observed only for cyclic trimers 1 when using columns of silica gel modified with pyrenylethyl, cyanopropyl, and other groups. Structural analysis of cyclic trimers 1 was carried out by means of NMR spectroscopy and X‐ray crystallography. Treatment of an η³‐allylpalladium complex with a cyclic trimer gave a tris(palladium) complex containing three η³‐allylpalladium groups inside the space, which indicated that the bipyridyl moieties inside the ring could work as bidentate metalloligands.     

7,7,8,8‐Tetraaryl‐o‐quinodimethane Stabilized by Dibenzo Annulation: A Helical π‐Electron System That Exhibits Electrochromic and Unique Chiroptical Properties

When two benzene rings are fused to a tetraaryl‐o‐quinodimethane skeleton, sterically hindered helical molecules 1 acquire a high thermodynamic stability. Because the tetraarylbutadiene subunit contains electron‐donating alkoxy groups, 1 undergo reversible two‐electron oxidation to 2 ²⁺, which can be isolated as deeply colored stable salts. Intramolecular transfer of the point chirality (e.g., sec‐butyl) on the aryl groups to helicity induces a diastereomeric preference in dications 2 b ²⁺ and 2 c ²⁺, which represents an efficient method for enhancing circular‐dichroism signals. Thus, those redox pairs can serve as new electrochiroptical response systems. X‐ray analysis of dication 2 ²⁺ revealed π–π stacking interaction of the diarylmethylium moieties, which is also present in solution. The stacking geometry is the key contributor to the chirosolvatochromic response.