Multifunctional Precursor Research Articles

Recent Approaches in the Synthesis of 5-Arylidene-2,4-thiazolidinedione Derivatives Using Knoevenagel Condensation

Abstract: 5-Arylidene-2,4-thiazolidinedione (5-A-TZD) is an emerging precursor molecule in medicinal chemistry for discovering multifunctional therapeutic agents. For synthesizing this precursor molecule, Knoevenagel Condensation (KC) is one of the most excellent tools in modern organic chemistry. The 5-A-TZD framework has a variety of therapeutic functions such as antidiabetic, anticancer, antimicrobial, and anti-inflammatory. As a result, several approaches and methods of KC have been established for the synthesis of this multifunctional precursor. However, the use of highly corrosive catalysts, prolonged reaction times, by-products formation, and poor product yields are the main drawbacks in 5-A-TZDs synthesis via KC. Therefore, several authors have been successfully established fast, effective, and environmentally sustainable protocols of KC using organic catalysts, inorganic catalysts, heterogeneous solid catalysts, ionic liquids (ILs), and bio-catalysts to synthesize 5-A-TZD derivatives with high conversion yield and selectivity. In this review, we have summarized the recent approaches for synthesizing 5-A-TZDs via KC and their therapeutic application as a precursor molecule in medicinal chemistry.

Metallasilsesquioxane-derived ultrathin porous carbon nanosheet 3D architectures via an “in situ dual templating” strategy for ultrafast sodium storage

It is the first time that metallasilsesquioxanes are introduced into the synthesis of porous carbon nanosheets. Lithium hepta(i-butyl)silsesquioxane trisilanolate is a multifunctional precursor for both carbon sources and templates with different dimensions.

Phenanthroline derivative based europium(III) covalently bonded silica hybrid material for high-selectivity sensing of anion and small organic molecule

A new polysilsesquioxane bridge (PhenOHSi) was synthesized here using 2-(2-hydroxyphenyl)-imidazo[4,5-f]-1,10-phenanthroline (PhenOH) and 3-(triethoxysilyl)propyl isocyanate respectively as a ligand of Eu3+ ion and a siloxane network precursor. Then, an organic–inorganic hybrid material covalently grafted with an Eu3+ complex (denoted as Eu(PhenOHSi)2Phen) was synthesized by coordination of an Eu3+ ion with a multifunctional precursor PhenOHSi and a second ligand Phen in a sol–gel process. This hybrid material was found to exhibit intensive red luminescence under UV light triggered by the ligand antenna effect. Further luminescent studies indicate that Eu(PhenOHSi)2Phen not only displays high sensitivity sensing targeted at fluoride ions, but also exhibits distinct solvent-dependent luminescent spectra with emission intensities that are significantly quenched by N,N-dimethylformamide.

N,S-Codoped hierarchical porous carbon spheres embedded with cobalt nanoparticles as efficient bifunctional oxygen electrocatalysts for rechargeable zinc-air batteries.

Rational design and fabrication of cost-effective, efficient bifunctional electrocatalysts is fundamentally important for the air cathode of metal-air batteries. Herein, a Co(ii) ion-driven self-assembly strategy is described for the synthesis of cobalt-based nanostructured transition metal compounds (Co-NTMCs) embedded in nitrogen and sulfur codoped hierarchical porous carbon submicrospheres (Co-NTMCs@NSC), where condensation of thiourea-ethylenediamine-formaldehyde resin (TEFR) is induced by Co(ii) ions which is simultaneously assembled with polydopamine to form a multifunctional precursor through coordinated interaction. The resulting Co-NTMCs@NSC sample comprises abundant hierarchical porous textures, a high content of active cobalt species including the nanoparticles of Co, Co3O4 and amorphous CoSx, and a considerable amount of defective structures. These characteristics lead to remarkable oxygen electrocatalytic activities, with a half-wave potential of +0.833 V vs. RHE, which is comparable to that of commercial Pt/C for the oxygen reduction reaction (ORR), and a lower overpotential of 284 mV than RuO2 at 10 mA·cm-2 for the oxygen evolution reaction (OER) in alkaline media. Furthermore, its operational stability is also much higher than that of commercial RuO2 and Pt/C catalysts. When used as a breathing air electrode for Zn-air batteries, Co-NTMCs@NSC shows a higher open-circuit voltage (1.509 V), higher discharge power density (262 mW cm-2) and better charge-discharge reversibility than commercial Pt/C. The results from the present work suggest that controlled assembly of functional polymers may be exploited for the preparation of doped carbon/metal nanoparticle nanocomposites as viable, high-performance catalysts for electrochemical energy technologies.

Chemical Foaming Coupled Self-Etching: A Multiscale Processing Strategy for Ultrahigh-Surface-Area Carbon Aerogels

Due to the unique structure, carbon aerogels have always shown great potential for multifunctional applications. At present, it is highly desirable but remains challenging to tailor the microstructures with respect to porosity and specific surface area to further expand its significance. A facile chemical foaming coupled self-etching strategy is developed for multiscale processing of carbon aerogels. The strategy is directly realized via the pyrolysis of a multifunctional precursor (pentaerythritol melamine phosphate) without any special drying process and multiple steps. In the micrometer scale, the macroporous scaffold structures with interconnected and strutted carbon nanosheets are built up by chemical foaming from decomposition of melamine, whereas the meso/microporous nanosheets are formed via self-etching by phosphorus-containing species. The delicately hierarchical structures and record-breaking specific surface area of 2668.4 m2 g-1 render the obtained carbon aerogels great potentials for absorption (324.1-593.6 g g-1 of absorption capacities for varied organic solvents) and energy storage (338 F g-1 of specific capacitance). The construction of such novel carbon nanoarchitecture will also shed light on the design and synthesis of multifunctional materials.

Self-catalytic Synthesis of ZnO Nanoparticles@SiO2 Composites with Controllable Fluorescence

ZnO nanoparticles@SiO2 (ZnO NPs@SiO2) composites have been prepared by a self-catalytic approach in a water–ethanol solution at near neutral conditions. A multifunctional precursor combining not only a silicon alkoxide and a metal carboxylate group, but also a protonated amine group was designed. The intramolecular protonated amine groups could act as catalytic sites for the hydrolysis and condensation of silicon alkoxides. Thus self-catalytic reactions would proceed spontaneously without the addition of any other catalyst. By adjusting the manner of adding the silica source, ZnO NPs with an average diameter of 2.61, 4.00, and 5.72 nm for ZnO NPs@SiO2 composites could be controllably synthesized. Accordingly, the different ZnO NPs@SiO2 composites displayed blue, green, and yellow three emission under ultraviolet light.

Ultrastable hydrogen evolution electrocatalyst derived from phosphide postmodified metal-organic frameworks

Developing non-precious metal catalyst with high activity, good stability and low cost for electrocatalytic hydrogen evolution reaction (HER) is critical for hydrogen product from water splitting. Here, we proposed a facile and effective approach to in situ synthesize highly efficient and ultrastable iron phosphide hybrids anchored inside a hollow N-P codoped carbon derived from MIL-101-NH2-Fe-P (not only acting as multifunctional precursor but also nanoscale confined space during pyrolysis) via one-step method for HER. The newly developed FexP@NPC catalyst exhibits high electrocatalytic activity and shows a nearly constant voltage with only less 0.1% increase at 10mAcm−2 after 90h in full water splitting cell with high Faradaic efficiency of near 100% and keep very similar level even after shelving 10 days.

Pyrrole-Terminated Ionic Liquid Surfactant: One Molecule with Multiple Functions for Controlled Synthesis of Diverse Multispecies Co-Doped Porous Hollow Carbon Spheres.

Rationally and efficiently controlling chemical composition, microstructure, and morphology of carbon nanomaterials plays a crucial role in significantly enhancing their functional properties and expending their applications. In this work, a novel strategy for simultaneously controlling these structural parameters was developed on the base of a multifunctional precursor approach, in which the precursor not only serves as carbon source and structure-directing agent, but also contains two heteroatom doping sites. As exemplified by using pyrrole-terminated ionic liquid surfactant as such precursor, in conjunction with sol-gel chemistry this strategy allows for efficiently producing well-defined hollow carbon spheres with controlled microstructure and chemical compositions. Remarkably, the dual-doping sites in confined silica channels provide an exciting opportunity and flexibility to access various doped carbons through simply anion exchange or altering the used oxidative polymerization agent, especially the multispecies codoped materials by combination of the two doping modes. All the results indicate that the described strategy may open up a new avenue for efficiently synthesizing functional carbon materials with highly controllable capability.

Synthesis and characterization of resorcinarene-centered amphiphilic A8B4miktoarm star copolymers based on poly(ε-caprolactone) and poly(ethylene glycol) by combination of CROP and “click” chemistry

Well-defined amphiphilic A8B4 miktoarm star copolymers with eight poly(ethylene glycol) chains and four poly(ε-caprolactone) arms (R-8PEG-4PCL) were prepared using “click” reaction strategy and controlled ring-opening polymerization (CROP). First, multi-functional precursor (R-8N3-4OH) with eight azides and four hydroxyls was synthesized based on the derivatization of resorcinarene. Then eight-PEG-arm star polymer (R-8PEG-4OH) was prepared through “click” reaction of R-8N3-4OH with pre-synthesized alkyne-terminated monomethyl PEG (mPEG-A) in the presence of CuBr/N,N,N′,N″,N″′- pentamethyldiethylenetriamine (PMDETA) in DMF. Finally, R-8PEG-4OH was used as tetrafunctional macroinitiator to prepare resorcinarene-centered A8B4 miktoarm star copolymers via CROP of ε-caprolactone utilizing Sn(Oct)2 as catalyst at 100 °C. These miktoarm star copolymers could self-assemble into spherical micelles in aqueous solution with resorcinarene moieties on the hydrophobic/hydrophilic interface, and the particle sizes could be controlled by the ratio of PCL to PEG. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2824–2833.

Novel lanthanide luminescent materials based on multifunctional complexes of 2-sulfanylpyridine-3-carboxylic acid and silica/titania hosts

Three different types of organic–inorganic hybrid materials formed by trivalent lanthanide (Ln3+ = Eu3+, Tb3+) complexes covalently grafted to silica-, titania-, or silica/titania-based hosts have been prepared and fully characterized. Since the organic ligand 2-sulfanylpyridine-3-carboxylic acid (SPC), a derivative of nicotinic acid, exhibits three potential binding sites (pyridine N, sulfhydryl S and carboxylic O), the multifunctional precursor can be prepared through the reaction of the carboxylic group with titanium alkoxide and the modification of the sulfhydryl group with silane crosslinking reagents. Thus, the organic–inorganic hybrid materials covalently grafted with Eu3+ or Tb3+ complexes are synthesized through coordination of the Ln3+ ions with the heterocyclic group in the multifunctional precursor during the sol–gel process. The obtained hybrid materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared (FTIR) spectroscopy, and photoluminescence (PL). The detailed PL studies showed that, compared with the titania-based hybrid materials (denoted as Ln–SPC–Ti), the silica- and silica/titania-based hybrid materials (denoted as Ln–SPCSi and Ln–SPCSi–Ti, respectively) exhibited higher luminescence intensity and emission quantum efficiency.

Preparation, characterization and luminescence properties of ternary europium complexes covalently bonded to titania and mesoporous SBA-15

A novel multifunctional precursor Ti-MAB-S15 (MAB = meta-aminobenzoic acid) were prepared through the reaction of the carboxylic group with titanium alkoxide, and the amino group was modified with the coupling agent 3-(triethoxysilyl)-propyl isocyanate (TEPIC) and covalently bonded to mesoporous silica SBA-15. Then, novel organic–inorganic luminescent mesoporous hybrid titania materials, designated as Eu(Ti-MAB-S15)2(NTA)3, were obtained by introducing the Eu(NTA)3·2H2O (NTA = 1-(2-naphthoyl)-3,3,3-trifluoroacetonate) complex into the hybrid materials Ti-MAB-S15via a ligand exchange reaction. FTIR, SAXRD, N2 absorption measurements, TEM, SEM, and photoluminescent spectra were characterized, and the results reveal that it has high surface area, is uniform in the mesostructure, and has good crystallinity. In addition, compared to the pure complex Eu(NTA)3·2H2O, the mesoporous hybrid titania material Eu(Ti-MAB-S15)2(NTA)3 exhibits longer luminescent lifetime and higher quantum efficiency, which indicates that the introduction of the multifunctional ligand Ti-MAB-S15 can sensitize the luminescence emission of the Eu3+ ions. Moreover, the luminescent mesoporous hybrid titania materials containing terbium ions, designated as Tb(Ti-MAB-S15)2(NTA)3, were also prepared, and were found to emit green photoluminescence characteristic of terbium ions.

Regulation of Proopiomelanocortin Gene Expression

Pituitary melanotroph and corticotroph cells produce and secrete peptides from the multifunctional precursor protein proopiomelanocortin (POMC). Stimulation of the secretory activity of both cell types involves production of cyclic 3′5′‐adenosine monophosphate (cAMP) and increases in the concentration of intracellular Ca2+. The increase in secretory activity is accompanied by enhanced expression of the POMC gene. Surprisingly, the POMC promoter lacks both cAMP‐responsive elements and Ca2+‐responsive elements through which the cAMP and Ca2+ signals could, in a relatively direct way, act on POMC gene expression. It is thus apparent that other, more indirect, mechanisms have evolved to utilize cAMP and Ca2+ signaling cascades to regulate POMC expression. This review gives an overview of the complex pathways and events that lead to the regulation of POMC gene expression in corticotrophs and melanotrophs. Another major site for POMC production is in hypothalamic neurons of the arcuate nucleus. In these neurons expression of the POMC gene relies on enhancer regions and responsive elements that differ from those utilized in the pituitary gland. In this review some attention will be given to progress made in unraveling the regulatory strategies acting on POMC expression in hypothalamic neurons. It is clear that the complexities of the promoter/enhancer structure of the POMC gene contribute to the versatility of this gene in participating in complex adaptation processes.

Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice

Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into saposin B's physiological functions, a specific deficiency was created in mice by a knock-in mutation of an essential cysteine in exon 7 of the prosaposin locus. No saposin B protein was detected in the homozygotes (B−/−) mice, whereas prosaposin, and saposins A, C and D were at normal levels. B−/− mice exhibited slowly progressive neuromotor deterioration and minor head tremor by 15 months. Excess hydroxy and non-hydroxy fatty acid sulfatide levels were present in brain and kidney. Alcian blue positive (sulfatide) storage cells were found in the brain, spinal cord and kidney. Ultrastructural analyses showed lamellar inclusion material in the kidney, sciatic nerve, brain and spinal cord tissues. Lactosylceramide (LacCer) and globotriaosylceramide (TriCer) were increased in various tissues of B−/− mice supporting the in vivo role of saposin B in the degradation of these lipids. CD68 positive microglial cells and activated GFAP positive astrocytes showed a proinflammatory response in the brains of B−/− mice. These findings delineate the roles of saposin B for the in vivo degradation of several GSLs and its primary function in maintenance of CNS function. B−/− provide a useful model for understanding the contributions of this saposin to GSL metabolism and homeostasis.

From Multifunctional Precursor to Novel Reaction Products: Oligimerization and Central Metal Ion Exchange Reaction of Ferrocenyl Carboxylate Complexes

A distinctive multifunctional precursor complex Zn(bafca)2(phen)(H2O), 1 (bafca− = α-benzamido-β-ferrocenylacrylic carboxylate; phen = 1,10-phenantholine), is synthesized. As an acceptor, it takes part in the oligimerization to produce a novel decanuclear Zn(II) cluster, [Zn(OCH3)(HOCH3)(bafca)]10·8H2O, 1A; as a donor, it undergoes the unusual central metal ion exchange reaction, resulting in a new Cd(II) skeleton, [Cd(bafca)2(phen)]2·8H2O, 1B. X-ray crystallographic analysis shows that the molecule of 1A consists of a centrosymmetric ring comprised of 10 Zn(II) ions held together by 10 μ2-methoxide, 10 μ2-methanol, 10 1,3-bridging bafca− ligands. In the ring, the 10 zinc atoms are approximately coplanar and are coordinated in a distorted octahedral manner by six oxygen donor atoms. Compound 1A is the analogue of Lippard’s famous “ferric wheel” [Fe(OMe)2(O2CCH2Cl)]10 of bivalent metal ions ( J. Am. Chem. Soc. 1990, 112, 9629; 1994, 116, 823), and its synthesis proves that the bivalent metal ions can also ...

Defective prodynorphin processing in mice lacking prohormone convertase PC2.

Prodynorphin, a multifunctional precursor of several important opioid peptides, is expressed widely in the CNS. It is processed at specific single and paired basic sites to generate various biologically active products. Among the prohormone convertases (PCs), PC1 and PC2 are expressed widely in neuroendocrine tissues and have been proposed to be the major convertases involved in the biosynthesis of hormonal and neural peptides. In this study we have examined the physiological involvement of PC2 in the generation of dynorphin (Dyn) peptides in mice lacking active PC2 as a result of gene disruption. Enzymological and immunological assays were used to confirm the absence of active PC2 in these mice. The processing profiles of Dyn peptides extracted from brains of these mice reveal a complete lack of Dyn A-8 and a substantial reduction in the levels of Dyn A-17 and Dyn B-13. Thus, PC2 appears to be involved in monobasic processing, leading to the generation of Dyn A-8, Dyn A-17, and Dyn B-13 from prodynorphin under physiological conditions. Brains of heterozygous mice exhibit only half the PC2 activity of wild-type mice; however, the levels of Dyn peptides in these mice are similar to those of wild-type mice, suggesting that a 50% reduction in PC2 activity is not sufficient to significantly reduce prodynorphin processing. The disruption of the PC2 gene does not lead to compensatory up-regulation in the levels of other convertases with similar substrate specificity because we find no significant changes in the levels of PC1, PC5/PC6, or furin in these mice as compared with wild-type mice. Taken together, these results support a critical role for PC2 in the generation of Dyn peptides.

Le lobe intermédiaire de l'hypophyse, modèle de communication neuroendocrinienne

The intermediate lobe of the pituitary is composed of a homogeneous population of endocrine cells, the melanotrophs, which secrete several bioactive peptides including alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. In contrast to most endocrine glands which are richly vascularized, the intermediate lobe of the pituitary contains very few blood vessels; in some species, the pars intermedia is virtually totally avascular. In contrast, pituitary melanotrophs are richly supplied by nerve fibers originating from the hypothalamus. The pars intermedia thus appears as a pure model of neuroendocrine communication, i.e. it is an archetype of the mode of transducing interface between the central nervous system and endocrine effectors. In mammalian species, different types of nerve terminals containing dopamine, norepinephrine, gamma-aminobutyric acid (GABA) and serotonin have been identified. In lower vertebrates, particularly in fish and amphibians, the pars intermedia is also innervated by peptidergic fibers which are though to take part in regulation of the secretory activity of the melanotroph. In these animals, the pars intermedia is regarded as a major center of neuroendocrine integration and an exceptional model to investigate the process of communication between the brain and the endocrine glands. The purpose of the present review is to summarize our current knowledge on the synthesis, processing and release of peptide hormones from pars intermedia cells and to survey the multiple regulatory mechanisms which are involved in the control of the activity of pituitary melanotrophs. Proopiomelanocortin, a multifunctional precursor. Pituitary melanotrophs synthetise a major precursor protein called proopiomelanocortin (POMC) which generates through proteolytic cleavage several biologically active peptides including adrenocorticotropic hormone (ACTH), endorphins and MSHs. In lower vertebrates, alpha-MSH is generally considered as the major hormone secreted by melanotrophs, in that it is involved in the process of skin colour adaptation. The post-translational processing of POMC, which yields to the mature hormones released by melanotrophs, includes a number of steps: glycosylation, phosphorylation, tissue-specific proteolytic cleavage, amidation and acetylation. Some of these posttranslational modifications can be regulated by neuroendocrine factors. For instance, in frogs, it has been shown that dopamine inhibits acetylation of alpha-MSH and thus reduces the secretion of the biologically active form of the peptide. The intermediate lobe of the pituitary: a model of neuroendocrine integration. In most vertebrate species, the intermediate lobe of the pituitary is innervated by catecholamine-containing fibers. In particular, the presence of dopaminergic nerve fibers has been observed in the pars intermedia of mammals and poikilotherms.(ABSTRACT TRUNCATED AT 400 WORDS)

Processing of thyrotropin-releasing hormone prohormone (pro-TRH) generates a biologically active peptide, prepro-TRH-(160-169), which regulates TRH-induced thyrotropin secretion.

Rat thyrotropin-releasing hormone (TRH) prohormone contains five copies of the TRH progenitor sequence Gln-His-Pro-Gly linked together by connecting sequences whose biological activity is unknown. Both the predicted connecting peptide prepro-TRH-(160-169) (Ps4) and TRH are predominant storage forms of TRH precursor-related peptides in the hypothalamus. To determine whether Ps4 is co-released with TRH, rat median eminence slices were perifused in vitro. Infusion of depolarizing concentrations of KCl induced stimulation of release of Ps4- and TRH-like immunoreactivity. The possible effect of Ps4 on thyrotropin release was investigated in vitro using quartered anterior pituitaries. Infusion of Ps4 alone had no effect on thyrotropin secretion but potentiated TRH-induced thyrotropin release in a dose-dependent manner. In addition, the occurrence of specific binding sites for 125I-labeled Tyr-Ps4 in the distal lobe of the pituitary was demonstrated by binding analysis and autoradiographic localization. These findings indicate that these two peptides that arise from a single multifunctional precursor, the TRH prohormone, act in a coordinate manner on the same target cells to promote hormonal secretion. These data suggest that differential processing of the TRH prohormone may have the potential to modulate the biological activity of TRH.

Proopiomelanocortin (POMC)-related peptides in the brain of the rainbow trout, Salmo gairdneri

We have investigated the presence of ACTH, α-MSH and β-endorphin, three peptides which derive from the multifunctional precursor protein proopiomelanocortin (POMC) in the brain of the rainbow trout Salmo gairdneri. Using both the indirect immunofluorescence and peroxidase-antiperoxidase techniques, a discrete group of positive cells was identified in the hypothalamus, within the anterior part of the nucleus lateralis tuberis. α-MSH-containing neurons represented the most abundant immunoreactive subpopulation. Coexistence of α-MSH, ACTH and β-endorphin was observed in the lateral part of the nucleus. ACTH- and β-endorphin-containing cells were mainly distributed in the rostral and caudal regions of the nucleus. In the medial portion of the nucleus lateralis tuberis, numerous cells were only stained for α-MSH. Moderate to dense plexuses of immunoreactive fibers were observed in the ventral thalamus and the floor of the hypothalamus. Some of these fibers projected towards the pituitary. The concentrations of ACTH, α-MSH and β-endorphin-like immunoreactivities were measured in microdissected brain regions by means of specific radioimmunoassays. Diencephalon, mesencephalon and medulla oblongata extracts gave dilution curves which were parallel to standard curves. The highest concentrations of POMC-derived peptides were found in the diencephalon (α-MSH: 4.28±0.43 ng/mg prot.; ACTH: 1.08±0.09 ng/mg prot.; β-endorphin: 1.02±0.1 ng/mg prot.), while lower concentrations were detected in the mesencephalon, medulla oblongata and telencephalon. The present results demonstrate that various peptides derived from POMC coexist within the same cell bodies of the fish hypothalamus. Taken together, these data suggest that expression and processing of POMC in the fish brain is similar to that occurring in pituitary melanotrophs.