Terminal Moiety Research Articles

Linker-length dependent intra/intermolecular coordination of synthetic zinc chlorophyll-a derivatives bearing a pyridine terminal in the C132-substituent

An ω-(m-pyridyl)alkyl group was introduced at the C132-methoxycarbonyl group of methyl pheophorbide-a as a chlorophyll-a derivative by exchange of the esterifying moiety. To avoid allomerization and epimerization of the C132-chiral center in the β-keto-ester moiety, a propyl group was substituted at the C132-position. The free bases were zinc-metalated to give zinc methyl 132-propyl-pheophorbides-a bearing an oligomethylene chain with a pyridyl terminal at the C132-position. Depending on the length of the alkyl chain between the terminal pyridine and C132-carboxylate moieties, the coordination of the m-pyridyl group with the central zinc atom in the stereochemically pure and fixed zinc chlorin–pyridine conjugates occurred in intra- or intermolecular fashions.

Catalytic Site-, Diastereo-, and Enantioselective Cascade Iodocyclization of 2-Geranylarenols.

A chiral amidophosphate-N-iodosuccinimide cooperative catalysis has been developed for the site-, diastereo-, and enantioselective iodocyclization of 2-geranylarenols with molecular iodine to give the corresponding iodo-containing polycyclic compounds with good levels of selectivity. This is the first example of a catalytic enantioselective iodocarbocyclization. A reactive chiral iodonium species is generated from molecular iodine via the dual halogen-bonding interactions with a chiral Lewis base and Lewis acid. The sterically demanding 3,3'-substituents of the chiral BINOL-derived amidophosphate are critical to induce the site-selective iodination at the less-hindered terminal alkenyl moiety of 2-geranylarenols.

Self-Assembly, Bioactivity, and Nanomaterials Applications of Peptide Conjugates with Bulky Aromatic Terminal Groups

The self-assembly and structural and functional properties of peptide conjugates containing bulky terminal aromatic substituents are reviewed with a particular focus on bioactivity. Terminal moieties include Fmoc [fluorenylmethyloxycarbonyl], naphthalene, pyrene, naproxen, diimides of naphthalene or pyrene, and others. These provide a driving force for self-assembly due to π-stacking and hydrophobic interactions, in addition to the hydrogen bonding, electrostatic, and other forces between short peptides. The balance of these interactions leads to a propensity to self-assembly, even for conjugates to single amino acids. The hybrid molecules often form hydrogels built from a network of β-sheet fibrils. The properties of these as biomaterials to support cell culture, or in the development of molecules that can assemble in cells (in response to cellular enzymes, or otherwise) with a range of fascinating bioactivities such as anticancer or antimicrobial activity, are highlighted. In addition, applications of hydrogels as slow-release drug delivery systems and in catalysis and other applications are discussed. The aromatic nature of the substituents also provides a diversity of interesting optoelectronic properties that have been demonstrated in the literature, and an overview of this is also provided. Also discussed are coassembly and enzyme-instructed self-assembly which enable precise tuning and (stimulus-responsive) functionalization of peptide nanostructures.

Synthesis and physico-chemical properties of dilateral flouro azo/ester four aromatic ring mesogens and their mixtures of liquid crystals

ABSTRACT Four series of di-flouro, namely; 4-substituted phenylazo-3-flouro phenyl-4′-n-alkoxy 3-flouro phenylazo benzoates (I n a-d) based on aromatic rings with the azo/ester/azo linkages core, were prepared and investigated for their mesomorphic properties. An alkoxy group with chain length varied from n = 6 to 16 is attached to the terminal phenylazobenzoate moiety and the other terminal is a compact group (X = –CH3O, –CH3, H and Br) attached to phenylazo moiety. The mesophases were investigated by DSC and POM and compared with previously investigated dilaterally methyl substituted analogues. Terminally unsubstituted and Br substituted analogues displayed dimorphic N and SmA phases, except the lower homologue (n = 6), while terminally – CH3O analogues exhibited monomorphic N phase. For terminally – CH3 substituted, compounds with n = 6–12 exhibited only N phase, while compounds with n = 14 and 16 displayed N and SmA phases. Meanwhile, the dilateral F substituents result in an enhancement in clearing thermal transitions compared with dilateral methyl substituents with a wide mesophase range. TGA analysis revealed that the prepared compounds are thermally stable within mesophase temperature range, except – CH3O, –CH3 and Br derivatives with n = 6. Binary mixtures of I6 a-d/I16 a-d derivatives were investigated. The photo-physical property was also studied.

NMR Characterization of Polyethylene Glycol Conjugates for Nanoparticle Functionalization.

The molecular weight, purity, and functionalization of polyethylene glycols are often characterized by 1H NMR spectroscopy. Oft-forgotten, the typical 1H NMR pulse sequence is not 13C decoupled. Hence, for large polymers, the 13C coupled 1H peaks arising from the repeating units have integrations comparable to that of the 1H of the terminal groups. Ignoring this coupling leads to erroneous assignments. Once correctly assigned, these 13C coupled 1H peaks can be used to determine both the molecular weight of the polymer and the efficacy of conjugation of a terminal moiety more accurately than the uncoupled 1H of the repeating unit.

Annealing of acetylene containing cyclotriphosphazene to generate nitrogen- and phosphorus-containing layered graphitic materials

A new strategy to access nitrogen- and phosphorus-containing layered graphitic materials from cyclotriphosphazene bearing reactive terminal acetylene moieties was developed.

Dimeric tetrabromo-p-quinodimethanes: synthesis and structural/electronic properties.

Despite their great potential as molecular building blocks for organic synthesis, tetrabromo-p-quinodimethanes (TBQs) are a relatively unknown family of compounds. Herein, we showcase a series of five derivatives incorporating two tetrabromo-anthraquinodimethane (TBAQ) units linked by π-conjugated spacers of different nature and length. The resulting dimers TBQ1-5 are fully characterised by means of thorough spectroscopic measurements and theoretical calculations. Interestingly, owing to the steric hindrance imposed by the four bulky bromine atoms, the TBAQ fragments adopt a characteristically warped geometry, somehow resemblant of a butterfly, and the novel dimers show a complex NMR pattern with signal splittings. To ascertain whether dynamic processes regarding fluxional inversion of the butterfly configurations are involved, first-principles calculations assessing the interconversion energy barriers are performed. Three possible stereoisomers are predicted involving two diastereomers, thus accounting for the observed NMR spectra. The rotational freedom of the TBAQ units around the π-conjugated linker influences the structural and electronic properties of TBQ1-5 and modulates the electronic communication between the terminal TBAQ moieties. The role of the linker on the electronic properties is investigated by Raman and UV-vis spectroscopies, theoretical calculations and UV-vis measurements at low temperature. TBQ1-5 are of interest as less-explored structural building precursors for a variety of scientific areas. Finally, the sublimation, self-assembly and reactivity on Au(111) of TBQ3 is assessed.

The sulfonadyns: a class of aryl sulfonamides inhibiting dynamin I GTPase and clathrin mediated endocytosis are anti-seizure in animal models.

We show that dansylcadaverine (1) a known in-cell inhibitor of clathrin mediated endocytosis (CME), moderately inhibits dynamin I (dynI) GTPase activity (IC50 45 μM) and transferrin (Tfn) endocytosis in U2OS cells (IC50 205 μM). Synthesis gave a new class of GTP-competitive dynamin inhibitors, the Sulfonadyns™. The introduction of a terminal cinnamyl moiety greatly enhanced dynI inhibition. Rigid diamine or amide links between the dansyl and cinnamyl moieties were detrimental to dynI inhibition. Compounds with in vitro inhibition of dynI activity <10 μM were tested in-cell for inhibition of CME. These data unveiled a number of compounds, e.g. analogues 33 ((E)-N-(6-{[(3-(4-bromophenyl)-2-propen-1-yl]amino}hexyl)-5-isoquinolinesulfonamide)) and 47 ((E)-N-(3-{[3-(4-bromophenyl)-2-propen-1-yl]amino}propyl)-1-naphthalenesulfonamide)isomers that showed dyn IC50 <4 μM, IC50(CME) <30 μM and IC50(SVE) from 12-265 μM. Both analogues (33 and 47) are at least 10 times more potent that the initial lead, dansylcadaverine (1). Enzyme kinetics revealed these sulfonamide analogues as being GTP competitive inhibitors of dynI. Sulfonadyn-47, the most potent SVE inhibitor observed (IC50(SVE) = 12.3 μM), significantly increased seizure threshold in a 6 Hz mouse psychomotor seizure test at 30 (p = 0.003) and 100 mg kg-1 ip (p < 0.0001), with similar anti-seizure efficacy to the established anti-seizure medication, sodium valproate (400 mg kg-1). The Sulfonadyn™ class of drugs target dynamin and show promise as novel leads for future anti-seizure medications.

A facile approach to create sensitive and selective Cu(ii) sensors on carbon fiber microelectrodes.

A facile platform derived from deposition of ethynyl linkers on carbon fiber microelectrodes has been developed for sensitive and selective sensing of Cu(ii). This study is the first to demonstrate the successful anodic deposition of ethynyl linkers, specifically 1,4-diethynylbenzene, onto carbon fiber microelectrodes. Multi-scan deposition of DEB on these microelectrodes resulted in an increased sensitivity and selectivity towards Cu(ii) that persists amidst other divalent interferents and displays sustained performance over four days while stored at room temperature. This method can be extended to other ethynyl terminal moieties, thereby creating a versatile chemical platform that will enable improved sensitivity and selectivity for a new frontier of biomarker measurement.

Alkaline cations dramatically control molecular hydrogelation by an amino acid-derived anionic amphiphile

Understanding the factors that control the formation of (supra)molecular hydrogels permits a rational tuning of their properties and represents a primary challenge for developing smart biocompatible soft materials. Hydrogel formation by molecular amphiphilic anions at millimolar concentrations is counterintuitive, considering the solubility of these species in water. Here we report hydrogel formation by a simple anionic molecular amphiphile and a rationale for the fibrillisation process observed. The studied molecule, DodValSuc, consists of a 12C alkyl chain, an l-valine unit and a terminal succinic acid moiety. Hydrogelation depends to a large degree on the nature and concentration of the alkaline cations present in the medium (Li+, Na+ or K+). As a result, gelation efficiency and properties like thermal stability or rheology are highly tunable using the alkaline cation present or its concentration as variables.A detailed study is reported, which includes the determination of minimum gelation concentration (MGC) by tabletop rheology, critical micelle concentration (CMC) using pyrene as a fluorescent probe, thermal stability (solubility) by 1H NMR, the morphology of the fibres by transmission electron microscopy (TEM), crystallinity by X-ray diffraction (XRD) and gel strength by oscillatory rheology. Additionally, dynamic light scattering (DLS) was used to evaluate the size of the micelles and permitted monitoring of the fibrillisation process.Altogether, the results are consistent with the formation of micelles that experience head crystallisation and subsequent aggregation into crystalline fibres. The alkaline cations play a crucial role in providing the cement that glues together the gelator molecules, making their concentration a critical parameter for gelation efficiency and properties. Furthermore, the gelation-promoting effects are inversely correlated with the size of the cations so that the highest thermal stability and rheological strength were found for the hydrogels formed in the presence of Li+.

Pseudo-irreversible butyrylcholinesterase inhibitors: Structure–activity relationships, computational and crystallographic study of the N-dialkyl O-arylcarbamate warhead

Alongside reversible butyrylcholinesterase inhibitors, a plethora of covalent butyrylcholinesterase inhibitors have been reported in the literature, typically pseudo-irreversible carbamates. For these latter, however, most cases lack full confirmation of their covalent mode of action. Additionally, the available reports regarding the structure–activity relationships of the O-arylcarbamate warhead are incomplete. Therefore, a follow-up on a series of pseudo-irreversible covalent carbamate human butyrylcholinesterase inhibitors and the structure–activity relationships of the N-dialkyl O-arylcarbamate warhead are presented in this study. The covalent mechanism of binding was tested by IC50 time-dependency profiles, and sequentially and increasingly confirmed by kinetic analysis, whole protein LC-MS, and crystallographic analysis. Computational studies provided valuable insights into steric constraints and identified problematic, bulky carbamate warheads that cannot reach and carbamoylate the catalytic Ser198. Quantum mechanical calculations provided further evidence that steric effects appear to be a key factor in determining the covalent binding behaviour of these carbamate cholinesterase inhibitors and their duration of action. Additionally, the introduction of a clickable terminal alkyne moiety into one of the carbamate N-substituents and in situ derivatisation with azide-containing fluorophore enabled fluorescent labelling of plasma human butyrylcholinesterase. This proof-of-concept study highlights the potential of this novel approach and for these compounds to be further developed as clickable molecular probes for investigating tissue localisation and activity of cholinesterases.

Simplified Y6-Based Nonfullerene Acceptors: In-Depth Study on Molecular Structure-Property Relation, Molecular Dynamics Simulation, and Charge Dynamics.

Two new Y6 derivatives of symmetrical YBO-2O and asymmetrical YBO-FO nonfullerene acceptors (NFAs) are prepared with a simplified synthetic procedure by incorporating octyl and fluorine substituents onto the terminal 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (INCN) moiety. By moving the alkyl substituents on the Y6 core to the terminal INCN moiety, the lowest unoccupied molecular orbital of the YBO NFAs increases without decreasing solubility, resulting in high open-circuit voltages of the devices. Molecular dynamics simulation shows that YBO-2O/-FO preferentially form core-core and terminal-terminal dimeric interactions, demonstrating their tighter packing structure and higher electron mobility than Y6, which is consistent with 2D grazing incidence X-ray scattering and space charge limited current measurements. In blend films, the hole transfer (HT) from YBO-2O/-FO to the polymer donor PM6 is studied in detail by transient absorption spectroscopy, demonstrating efficient HT from YBO-FO to PM6 with their suitable energy level alignment. Despite the simplified synthesis, YBO-FO demonstrates photovoltaic performance similar to that of Y6, exhibiting a power conversion efficiency of 15.01%. Overall, this design strategy not only simplifies the synthetic procedures but also adjusts the electrical properties by modifying the intermolecular packing and energy level alignment, suggesting a novel simplified molecular design of Y6 derivatives.

Pocket structures of surface protrusions shared among serologically distinct nervous necrosis viruses (NNVs) were predicted in silico to bind to sialylated N-glycans, a host cellular receptor

Nervous necrosis virus (NNV), one of the simplest spherical RNA-viruses, causes high mortality in aquaculture facilities worldwide. In this study, we investigated changes in the infectivity and reactivity of serologically distinct NNVs after treatment with 2.0 M urea, which was used as a means to predict a site or sites on surface protrusions responsible for NNV infection. Antigenicity of NNVs declined significantly after urea treatment but their infectivity was maintained, regardless of serological distinctions. The ability of urea-treated NNVs to be neutralized by antisera was also maintained, regardless of serological distinction. Moreover, weak but reliable cross-neutralizing reactions were observed between serologically distinct NNVs even after urea-treatment. These results suggested that common epitopes resistant to urea-treatment were shared among serologically distinct NNVs. Furthermore, two highly conserved amino-acid stretches among NNVs were revealed, and these stretches surround the pocket structures at the apex of surface protrusions. Molecular docking analysis showed that the pocket structure of surface protrusions was a site for maximally stable binding with the terminal moiety of sialylated N-glycans, a common cellular receptor for serologically distinct NNVs. Based on these results, the pocket structures on surface protrusions of NNVs, appear to be sites responsible for binding to sialylated N-glycans. Contrarily, a red-spotted grouper NNV (RGNNV)-specific MAb, neutralized naïve RGNNV but not the urea-treated RGNNV, suggesting that the epitope for this MAb was not present in the pocket structures. This suggests that disappearance of NNV infectivity due to binding with this MAb was the result of indirect inhibition of binding to the cellular receptor.

Coumarin-Ensembled Vanadium(V) Compounds and Their Affinity Studies Toward Biological Thiols Probed by Fluorescence Spectroscopy.

Fluorescence spectroscopic studies of a pair of new oxido-vanadium(V) compounds with biological thiols, such as homocysteine (Hcy), cysteine (Cys), and glutathione (GSH), have been investigated in this article. Despite notable progress in vanadium-thiol chemistry, no attention has been paid to exploring vanadium-based optical probes to study their interaction with biothiols. For this purpose, two oxido-vanadium(V) compounds, 1 and 2, have been prepared involving a tridentate ONO donor-based luminescent coumarin-derived ligand. Single crystal X-ray diffraction analysis, NMR (1 H, 13 C, and 51 V) spectroscopy, XPS, and DFT calculations have been used to establish their identities. The vanadium center in these compounds has a distorted octahedral environment. In compound 2, a methanol molecule is coordinated to the vanadium(V) center in the trans position of the terminal oxido moiety. The latter exerts a strong trans-labilizing influence on the coordinating methanol. Both 1 and 2 are weakly fluorescent. Photophysical investigations of the vanadium complexes in aqueous media at physiological pH (7.4) in the presence of various biothiols and amino acids showed significant fluorescence enhancement (83-fold) of the vanadium complexes, specifically with Hcy. The specific affinity of the complexes for Hcy remained unchanged even in the presence of other biothiols and amino acids. Kinetic investigation reveals pseudo-first order behavior of the compound with Hcy. Mechanistic studies have manifested that Hcy-induced reduction triggers the decomplexation of the vanadium compound, followed by hydrolysis and subsequent cyclization. Time-correlated single photon counting suggested that the radiative rate constant (kr ) of 1 and 2 in the presence of Hcy serves as the prime factor for the fluorescence enhancement of the medium. Compound 1 has been tested efficiently for Hcy measurement in blood plasma rendering it suitable for practical applications.

Efficient production of lacto-N-fucopentaose III in engineered Escherichia coli using α1,3-fucosyltransferase from Parabacteroides goldsteinii

Lacto-N-fucopentaose III (LNFP III) is a human milk oligosaccharide (HMO) with potential health benefits in infants, including in immune development and modulation of the intestinal environment. Low-cost fermentative production of various HMOs from lactose by engineered Escherichia coli has attracted attention, but few reports have investigated long-chain HMO production, such as of the pentasaccharide LNFP III. LNFP III is synthesized by α1,3-fucosyltransfer reaction to the glucosamine (GlcNAc) moiety in the lacto-N-neotetraose (LNnT) skeleton by α1,3-fucosyltransferase (α1,3-FucT). However, the known α1,3-FucTs also transfer fucose to the reducing terminal glucose moiety of LNnT or the starting material lactose, resulting in various byproducts. Here, we found a useful α1,3-FucT from Parabacteroides goldsteinii (PgsFucT), which is only reactive for GlcNAc in the N-acetyllactosamine (LacNAc) skeleton in vivo. On the basis of sequence alignment with a FucT of known structure, we also generated α1,3-FucT variants with altered reactivity for LacNAc or lactose. An E. coli strain heterologously expressing PgsFucT accumulated 3.84 g/L of LNFP III after 48 h of culture in a 3-L jar-fermenter. The amounts of various byproduct sugars were remarkably decreased compared with a strain expressing the previously characterized α1,3-fucT from Bacteroides fragilis.

Synthesis and characterization of a polystyrene-type polymer bearing a cyclic perfluoroalkylene group

Perfluoroalkyl-containing aromatic compounds are predicted to have fascinating material properties. In this work, a styrene derivative bearing a cyclic perfluoroalkylene group, –(CF2)4–, was synthesized and polymerized to afford the corresponding polymer. The styrene derivative was obtained via the Ullmann coupling of I–(CF2)4–I with 3′-bromo-4′-iodoacetophenone, NaBH4 reduction of the ketone moiety, and dehydration using P4O10. Free-radical polymerization (FRP) of the styrene derivative afforded polymer with number-average molecular weight (Mn) and dispersity index (DI) of 1.1 × 104 and 3.1, respectively. The thermal stability of the synthesized polymer (Td10% 359 °C, Tg 149 °C) was greater than the previously reported n-C4F9-substituted polystyrene (Td10% 296 °C, Tg 19 °C). The increased thermal stability of the newly synthesized polymer is hypothesized to arise from the lack of terminal CF3 moieties. The cyclic perfluoroalkylene-substituted polystyrene exhibited hydro- and oleo-phobicities comparable to those of the n-C4F9-substituted polystyrene, suggesting that the introduction of cyclic perfluoroalkylene groups instead of the commonly used Rf groups may have the potential to develop thermo-resistant polymers with hydro- and lipo-phobicity. Thew newly synthesized polymer is suitable for a variety of applications requiring high-Tg optical polymeric materials.

Design and synthesis of ether derivatives of spliceostatin A and their biological evaluation towards prostate cancer treatment

To confirm the hypothesis that the terminal epoxide structure of spliceostatin A may be active through hydrogen bond formation, we designed and synthesized novel ether derivatives of spliceostatin A, whose terminal epoxide is replaced with an ether-based moiety capable of hydrogen bond formation. The results of biological evaluation against AR-V7 and the conformational analysis of each derivative suggest that the terminal epoxide moiety of spliceostatin A expresses its activity through covalent bond formation rather than hydrogen bond formation.

Electron-Deficient Polycyclic Molecules via Ring Fusion for n-Type Organic Electrochemical Transistors.

The primary challenge for n-type small-molecule organic electrochemical transistors (OECTs) is to improve their electron mobilities and thus the key figure of merit μC*. Nevertheless, few reports in OECTs have specially proposed to address this issue. Herein, we report a 10-ring-fused polycyclic π-system consisting of the core of naphthalene bis-isatin dimer and the terminal moieties of rhodanine, which features intramolecular noncovalent interactions, high π-delocalization and strong electron-deficient characteristics. We find that this extended π-conjugated system using the ring fusion strategy displays improved electron mobilities up to 0.043 cm2 V-1 s-1 compared to our previously reported small molecule gNR, and thereby leads to a remarkable μC* of 10.3 F cm-1 V-1 s-1 in n-type OECTs, which is the highest value reported to date for small-molecule OECTs. This work highlights the importance of π-conjugation extension in polycyclic-fused molecules for enhancing the performance of n-type small-molecule OECTs.

Electron‐Deficient Polycyclic Molecules via Ring Fusion for n‐Type Organic Electrochemical Transistors

AbstractThe primary challenge for n‐type small‐molecule organic electrochemical transistors (OECTs) is to improve their electron mobilities and thus the key figure of merit μC*. Nevertheless, few reports in OECTs have specially proposed to address this issue. Herein, we report a 10‐ring‐fused polycyclic π‐system consisting of the core of naphthalene bis‐isatin dimer and the terminal moieties of rhodanine, which features intramolecular noncovalent interactions, high π‐delocalization and strong electron‐deficient characteristics. We find that this extended π‐conjugated system using the ring fusion strategy displays improved electron mobilities up to 0.043 cm2 V−1 s−1 compared to our previously reported small molecule gNR, and thereby leads to a remarkable μC* of 10.3 F cm−1 V−1 s−1 in n‐type OECTs, which is the highest value reported to date for small‐molecule OECTs. This work highlights the importance of π‐conjugation extension in polycyclic‐fused molecules for enhancing the performance of n‐type small‐molecule OECTs.

Spectroscopic and DFT investigations: Mesogenic alpha-Naphthyl derivatives with central cinnamate and ester linkages

Two novel mesomorphic homologous series of cinnamates and esters with terminal naphthalene derivatives: (E)-naphthalen-1-yl 3-(4-(alkoxy)phenyl)acrylate (I) and naphthalen-1-yl 4-(alkoxy)benzoate(II),were prepared and analyzed by standard spectroscopic characterization like UV, FT-IR,NMR,DSC,POM, and DFT studies. All the compounds with varying alkyl chain length exhibit mesomorphism with naphthalene attachment at the other terminal. In series I, n-ethoxy to n-butyloxy derivatives exhibit a monotropic nematic mesophase, whereas n-propyloxy and n-butyloxy derivatives exhibit a monotropic smectic A mesophase. Schlieren nematic and Smectic A mesophase commence from n-pentyloxy derivatives as enantiotropic and persist up to the last member synthesized. In series II, n-ethoxy to n-butyloxy derivatives are non-mesogenic, while both monotropic smectic A mesophase and schlieren nematic mesophase commence from n- pentyloxy derivatives as enantiotropic and persist up to the last member synthesized. Comparison with other homologous help to evaluate the effects of central cinnamate/ester linkage on mesomorphism, polarizability. We also use length/breadth (L/B) ratio from the MM2 models to gain understanding of the steric effect of the terminal naphthalene moiety. Furthermore, all the derivatives were geometrically optimized via time-dependent density functional theory (TD-DFT) at the B3LYP/6–31 G (d,p) computation also recorded the polarizability, interaction energy, HOMO – LUMO orbital energy gap.