Alkylthio Substituents Research Articles

Design, synthesis and evaluation of pyridine-based chromatographic adsorbents for antibody purification

The structure-based design and synthesis of four series of adsorbents for antibody purification by affinity chromatography has been investigated. The structures of 10 ligands were based on pyridine compounds that possessed thioalkyl substituents containing a primary amine, which was required for immobilisation of the ligands onto an epoxy-activated matrix (epoxy-Sepharose Fast Flow®). These new adsorbents were screened in monoclonal antibody binding assays in order to determine optimal buffer conditions for capture and elution under static and dynamic adsorption conditions. From batch binding measurements, the binding affinities, KD's, were found to be in the range of 3–5μM and the maximum capacities, qm's were between 12 and 30mgmAb/mL resin, depending on the substitution pattern of the thioalkylamine in the N-heterocyclic ring structure of the ligands. The amount of monoclonal antibody bound and eluted under overload conditions was influenced by the concentration of the sample loaded, the flow rate at which the sample was applied and the loading/volume. Further, the ability of these new adsorbents to selectively capture monoclonal antibodies of the class IgG1 from supernatants derived from genetically engineered CHO cells cultured in chemically defined media was investigated, documenting efficient capture and recovery of the mAb.

Molecular Suction Pads: Self‐Assembled Monolayers of Subphthalocyaninatoboron Complexes on Gold

Subphthalocyaninatoboron complexes with six long-chain alkylthio substituents in their periphery are applicable for the formation of self-assembled monolayers (SAMs) on gold. Such films are prepared from solution with the axially chlorido-substituted derivatives and characterised by near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results are in accord with the formation of SAMs assembled by the chemisorption of both covalently bound thiolate-type as well as coordinatively bound thioether units. The adsorbate molecules adopt an essentially flat adsorption geometry on the substrate, resembling a suction pad on a surface.

Self-Assembly, Chromic Properties, and Nanostructure Formation of Tetrathiafulvalene-Fused Dodecadehydro[18]annulenes

Abstract Multifunctional dodecadehydrotris(tetrathiafulvaleno)[18]annulenes 1b–1d, which have six peripheral butylthio substituents or six ester substituents, were synthesized together with the corresponding [12]annulene 2c. The [18]annulenes 1b–1d easily formed stacked dimers and higher oligomers in solution via nanoscopic phase separation among the π-frame, ester or alkylthio substituents, and inner sphere to show solvatochromism and thermochromism. Furthermore, the strong self-aggregation of their oxidized radical cations in solution resulted in electrochromism depending on the formation of various types of mixed-valence states and π-dimers. Interestingly, self-aggregation of the [18]annulenes 1b–1d in amphiphilic media such as THF–H2O either produced fibrous structures in the case of the hexabutylthio derivative 1b and hexabutyl ester 1c or resulted in the temperature hysteresis of the color, UV–vis absorptions, and 1H NMR signals obtained in solution in the case of the hexaoctyl ester 1d which forms no fiber and precipitate under similar conditions. It is noted that fibers of the hexabutyl ester 1c can be aligned in a magnetic field using the large diamagnetic response of the [18]annulene frame for the driving force. A small difference in the substituents of 1b–1d causes a remarkable change in either their solvato- and electrochromism or nanostructure formation of 1b–1d based on the self-assembling nature both in solution and in the solid state.

Self‐Assembled Monolayers of Single‐Molecule Magnets [Tb{Pc′(SR)8}2] on Gold

AbstractThe magnetic properties of the bis(phthalocyaninato)terbium complexes [Tb{Pc′(SR)8}2] (1) containing eight β‐positioned long‐chain alkylthio substituents SR (a: R=n‐C8H17, b: R=n‐C12H25) were studied by SQUID measurements, which revealed that both compounds are single‐molecule magnets with an effective energy barrier for spin reversal significantly higher than that found for pristine bis(phthalocyaninato)terbium [Tb(Pc)2]. Thin films on gold were fabricated from 1 a and 1 b by chemisorption from solution and were characterised by near‐edge X‐ray absorption fine structure (NEXAFS) and X‐ray photoelectron spectroscopy (XPS). In the case of 1 a, atomic force microscopy (AFM) was used in addition. The results are in accord with the formation of self‐assembled monolayers which contain the macrocyclic rings mainly in an approximately horizontal orientation. The chemisorption is primarily due to the peripheral SR substituents, giving rise to coordinatively bound thioether units, whose alkyl chains are in an almost parallel orientation with respect to the surface. In the case of 1 b, covalently attached thiolate units were also observed, indicating that the chemisorption process can lead to carbon–sulfur bond cleavage. In addition, the crystal structure of 1 a was determined.

Influence of Solvent and Bridge Structure in Alkylthio‐Substituted Triphenylamine Dyes on the Photovoltaic Properties of Dye‐Sensitized Solar Cells

Three new triphenylamine dyes that contain alkylthio-substituted thiophenes with a low bandgap as a π-conjugated bridge unit were designed and synthesized for organic dye-sensitized solar cells (DSSCs). The effects of the structural differences in terms of the position, number, and shape of the alkylthio substituents in the thiophene bridge on the photophysical properties of the dye and the photovoltaic performance of the DSSC were investigated. The introduction of an alkylthio substituent at the 3-position of thiophene led to a decrease in the degree of redshift and the value of the molar extinction coefficient of the charge-transfer band, and the substituent with a bridged structure led to a larger redshift than that of the open-chain structure. The introduction of bulky and hydrophobic side chains decreased the short-circuit photocurrent (J(sc)), which was caused by the reduced amount of dye adsorbed on TiO(2). This resulted in a decrease in the overall conversion efficiency (η), even though it could improve the open-circuit voltage (V(oc)) due to the retardation of charge recombination. Furthermore, the change in solvents for TiO(2) sensitization had a critical effect on the performance of the resulting DSSCs due to the different amounts of dye adsorbed. Based on the optimized dye bath and molecular structure, the ethylene dithio-substituted dye (ATT3) showed a prominent solar-to-electricity conversion efficiency of 5.20%.

Liquid crystalline octasubstituted lead(ii) phthalocyanines: effects of alkoxy and alkylthio substituents on film alignment and electrical properties

Octasubstituted lead(II) phthalocyanines containing alkylthio- and alkoxy- groups in peripheral positions have been synthesized and characterized using 1H and 13C NMR, UV-Vis, IR and mass spectroscopies as well as elemental analysis. The mesogenic properties of the octasubstituted lead(II) phthalocyanines have been investigated by differential scanning calorimetry, polarizing optical microscopy, and X-ray diffraction. The sandwich structures ITO/PbPc/In were prepared to investigate the J(V) characteristics of thin films of these molecules. The dissimilar behavior of the films before and after heat-treatment is expected to result in changing the alignment inside the columnar stacking of the molecules in the films.

Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa quorum sensing

Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure γ-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The γ-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations.

Synthesis and evaluation of 1-cyclopropyl-2-thioalkyl-8-methoxy fluoroquinolones

Novel fluoroquinolone derivatives substituted with a 2-thioalkyl moiety, with and without a concomitant 3-carboxylate group, were synthesized to evaluate the effect of C-2 thioalkyl substituents on gyrase binding and inhibition. The presence of a 2-thioalkyl group universally decreased activity as compared to parent fluoroquinolones. However, with derivatives of moxifloxacin the presence of either a 2-thioalkyl group or a 3-carboxylate moiety increased activity over the 2,3-unsubstituted derivative. Energy minimization of structures provides an explanation for relative activities of fluoroquinolones having a C-2 thio moiety.

A Successful Chemical Strategy To Induce Oligothiophene Self-Assembly into Fibers with Tunable Shape and Function

Functional supramolecular architectures for bottom-up organic nano- and microtechnology are a high priority research topic. We discovered a new recognition algorithm, resulting from the combination of thioalkyl substituents and head-to-head regiochemistry of substitution, to induce the spontaneous self-assembly of sulfur overrich octathiophenes into supramolecular crystalline fibers combining high charge mobility and intense fluorescence. The fibers were grown on various types of surfaces either as superhelices or straight rods depending on molecular structure. Helical fibers directly grown on a field effect transistor displayed efficient charge mobility and intrinsic 'memory effect'. Despite the fact that the oligomers did not have chirality centers, one type of hand-helicity was always predominant in helical fibers, due to the interplay of molecular atropisomerism and supramolecular helicity induced by terminal substituents. Finally, we found that the new sulfur overrich oligothiophenes can easily be prepared in high yields through ultrasound and microwave assistance in green conditions.

Phthalocyaninato complexes with peripheral alkylthio chains: Disk-like adsorbate species for the vertical anchoring of ligands onto gold surfaces

Thin metalorganic films were prepared on gold by self-assembly of thioether-functionalised phthalocyaninato complexes from solution. The phthalocyaninato ligands used contain eight peripheral, β-positioned, alkylthio substituents SR (1a: R=n-C8H17, 1b: R=n-C12H25), which serve as headgroups for surface binding and promote lateral assembly, while the disk-like phthalocyaninato core offers the scope for the attachment of axial ligands to the adsorbed molecules. This process was mimicked by coordination of pyridine (Py) to [Zn(1a)] and [Zn(1b)], respectively. The crystal structures of the products [Zn(1a)(Py)] and [Zn(1b)(Py)] were determined. The crystal structures of 4,5-bis(octylthio)phthalodinitrile and 4,5-bis(dodecylthio)phthalodinitrile were also determined. The films fabricated from [Mn(1a)Cl] and [Mn(1b)Cl] on gold were characterised by XPS, ToF-SIMS and NEXAFS spectroscopy, which revealed the presence of well-defined and homogeneous self-assembled monolayers (SAMs), whose constituents are bound to the substrate by thioether–gold linkages. The orientation of the macrocycles is predominantly parallel to the surface. Strong electronic interaction of the manganese(III) centre with the substrate leads to Cl loss upon adsorption and its reduction to MnII.

The synthesis and electrochemical study of novel phthalocyanines substituted with a crown ether and alkyl chains

A new class of soluble unsymmetrically substituted metallophthalocyanines (M = Zn, Ni, Co) bearing a crown ether and six alkylthio substituents was synthesized and their electrochemical and spectroelectrochemical properties studied. Cyclic and square wave voltammetry revealed well-defined ligand-based oxidation and reduction processes within the complexes. Assignment of the redox processes was performed by in-situ spectroelectrochemical measurements. The disappearance of the redox processes for the monomeric species and the observation of new waves indicated that intermolecular dimer formation occurred during the potentiometric titration of the complexes with K + and Na + ions.

Role of the hydrophobicity on the thermodynamic and kinetic acidity of Fischer thiocarbene complexes

Rate constants for the reversible deprotonation of (CO)(5)W=C(SR)CH(3) (W-SR) by OH(-), water and a number of primary aliphatic and secondary alicyclic amines, have been determined in 50% MeCN:50% water at 25 degrees C. In addition, solvation energy and proton affinities values for M-SR (M = Cr and W) in the gas phase and in acetonitrile have been computed at DFT level. Although there is not a linear correlation between the calculated proton affinities and the measured pK(a)s, the calculations reveal that when solvent effects are taken into account the substituted compounds studied show differences in their proton affinities. There is a good correlation between the change in cavitation energy (DeltaG(cav)) for the Fischer carbene complexes and log P of the thioalkyl substituents. In proton transfer reactions with amines, steric effects are more important for W complexes with respect to their Cr analogues as a consequence of differences in transition state progress. On the other hand, in reactions with OH(-), hydrophobicity of the R substituent is responsible for the observed changes in intrinsic kinetic acidities, which is supported by the good correlation obtained between log k(0) and log P. W complexes are more sensitive to hydrophobic effects due to the tighter solvation sphere with respect to their Cr counterparts. However, in the limit of log P = 0, the energy involved in the solvent reorganization process is the same regardless of the metal.

New Double-Decker Phthalocyanine Metallomesogens

The valence state and the mesomorphic behaviors of a homologous series of new cerium phthalocyanine double-decker complexes bearing thioalkyl substituents are described. Spectroscopic studies and Single crystal X-Ray crystallography data revealed that the metal center in this lanthanide double-decker complex is tetravalent making the whole molecule neutral and the two ligands structurally equivalent. As a consequence, the thermal stability of their mesophase is enhanced compared to those of other lanthanide phthalocyanine complexes. Moreover, these compounds show a strong tendency towards homeotropic alignment of their hexagonal columnar (Colh) mesophase on a glass substrate, which persist at room temperature (glass transition).

Investigation of the synthetic and mechanistic aspects of the highly stereoselective transformation of α-thioamides to α-thio-β-chloroacrylamides

Treatment of a series of alpha-thioamides with N-chlorosuccinimide results in efficient transformation to the analogous alpha-thio-beta-chloroacrylamides. The mechanistic pathway has been established through isolation and characterisation of intermediate compounds. The scope of the transformation has been explored-aryl and alkylthio substituents, primary, secondary and tertiary amides can be employed. In most instances, the chloroacrylamides are formed exclusively as the Z-stereoisomer; however, with tertiary propanamides or with amides derived from butanoic or pentanoic acid a mixture of E- and Z-stereoisomers is formed.

Design, synthesis, and biological evaluation of substituted 2-alkylthio-1,5-diarylimidazoles as selective COX-2 inhibitors

A new type of 1-aryl-5-(4-methylsulfonylphenyl)imidazoles, possessing C-2 alkylthio (SMe or SEt) substituents, were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti-inflammatory activity. The compound, 1-(4-bromophenyl)-5-(4-methylsulfonylphenyl)-2-methylthioimidazole ( 11g), was the most potent and selective COX-2 inhibitor (COX-2 IC 50 = 0.43 μM with no inhibition of COX-1 up to 25 μM) relative to the reference drug celecoxib (COX-2 IC 50 = 0.21 μM with no inhibition of COX-1 up to 25 μM) and also showed very good anti-inflammatory activity compared to celecoxib in carrageenan-induced rat paw edema assay.

Conducting Polymers Based on Alkylthiopyrroles

Three 3,4-bis(alkylthio)pyrroles (5a−c) were synthesized by a nonclassical pyrrole ring formation reaction followed by alkylation of the dithiol-2-one functional group. UV−vis absorption studies together with time dependent density-functional theory (TD-DFT) computations suggest that the monomers (5a−c) display low-energy π−σ* transitions (5a, 254 nm; 5b, 232 nm; 5c, 240 nm) compared to pyrrole (208 nm). Cyclic voltammetry investigations show that the monomers 5a−c possess significantly lower oxidation potentials (0.60 V for 5a, 0.58 V for 5b, and 0.71 V for 5c) than unsubstituted pyrrole (1.0 V). The corresponding polymers were successfully prepared by anodic electropolymerization and/or chemical oxidation (FeCl3 as oxidant) and investigated by cyclic voltammetry, spectroelectrochemistry and in situ conductivity studies. Our investigations of monomeric 3,4-disubstituted pyrroles and corresponding polymers suggest that the electron donating alkylthio substituents at the 3- and 4-positions of the pyrrole r...

Push-Pull-Substituted Oligo(2,5-thienyleneethynylene)s

Oligo(2,5-thienyleneethynylene)s (OTE) with terminal donor-acceptor substitution were synthesized by applying Sono-gashira-Hagihara reactions and a protection group technique. The combination of the alkylthio and nitro substituents provides a DAOTE series, whose long-wavelength absorption shows a monotonous bathochromic effect for increasing numbers n of repeat units. The convergence limit is already reached for n = 3.

A new double-decker phthalocyanine mesogen

The valence state and the mesomorphic behaviour of a new cerium phthalocyanine double-decker complex bearing thioalkyl substituents are described and spectroscopic studies have revealed that the metal center in this lanthanide double-decker complex is tetravalent making the whole molecule neutral.

Design, synthesis, and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4 H-1,2,4-triazoles as selective COX-2 inhibitors

A new type of 4,5-diaryl-4 H-1,2,4-triazole, possessing C-3 thio and alkylthio (SH, SMe or SEt) substituents, was designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti-inflammatory activity. The compound, 3-ethylthio-5-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)-4 H-1,2,4-triazole ( 10d), exhibited a high in vitro selectivity (COX-1 IC 50 = 20.5 nM; COX-2 IC 50 = 1.8 nM; SI = 11.39) relative to the reference drug celecoxib (COX-1 IC 50 = 3.7 nM; COX-2 IC 50 = 2.2 nM; SI = 1.68) and also showed good anti-inflammatory activity compared to celecoxib in a carrageenan-induced rat paw edema assay.

Synthesis, characterization, conduction and gas sensing properties of novel multinuclear metallo phthalocyanines (Zn, Co) with alkylthio substituents

Compound 1 has been prepared by the reaction of 4-nitrophthalonitrile and 2-nitro-2-methyl-1,3-propanediol by the common method of nucleophilic substitution of an activated nitro group in an aromatic ring. Interesting binuclear metallophthalocyanines (M = Zn and Co), compounds 2 and 3, respectively, of a new type have been synthesized from compound 1, 4,5-bis(hexylthio)phthalonitrile, and the corresponding metal salts [Zn(OAc) 2 and CoCl 2] by the method of statistically mixed condensation. Compound 2 was converted to the tetranuclear zinc (II) phthalocyanine 4 by the reaction with NaOH solution and activated zinc powder in a mixture of MeOH and THF as the solvent. Impedance spectroscopy (IS) and d.c conductivity ( σ d.c) measurements were performed on spin coated films of these compounds as a function of temperature (290–400 K) and frequency (40–10 5 Hz.) The sensing properties for volatile organic compounds (VOCs) were also investigated. Although the d.c conductivity shows typical Arrehenius behaviour for compound 2, a discontinous point was observed in the slope of ln σ d.c versus 1/ T plot for compound 4. Unlike the films of 2 and 4, the d.c behaviour of compound 3 obeys the variable range hopping (VRH) model. At room temperature, a curved line was observed from the complex plane plots of impedance for all compounds. These curved lines transformed into a full semicircle with increasing temperature. The a.c conductivity of the films is represented by the form ω s . The dependency of the frequency exponent s on temperature suggests a correlated barrier hopping. A sensor using compound 4 as the sensing layer had the highest sensitivity for all volatile organic compounds investigated and showed complete reversibility even at room temperature. The results indicated that the film of compound 4 has potential as a sensitive coating for the monitoring of VOC vapours.