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The lack of functional groups or binding sites largely hindered the broad application of microporous organic networks (MONs). Herein, we report the fabrication of the sulfonate group-enriched magnetic MON composite (MMON-SO 3 H@SO 3 Na) via the combination of the sulfonic acid group containing the monomer and thiol-yne click postmodification for efficient magnetic solid-phase extraction (MSPE) of benzimidazole fungicides (BZDs) from complex sample matrices. The well-defined core-shell-structured MMON-SO 3 H@SO 3 Na was obtained and served as an advanced adsorbent for MSPE for concentrating and monitoring trace BZDs. The MMON-SO 3 H@SO 3 Na with numerous sulfonate groups provides plenty of ion-exchange, hydrogen-bonding, and π-π sites, leading to the favorable affinity to BZDs via multiple interaction mechanisms. The MMON-SO 3 H@SO 3 Na-based MSPE-high-performance liquid chromatography method afforded a wide linear range, low limits of detection, large enrichment factors, good precisions, and reusability for BZDs. Trace BZDs in complex vegetables and fruit samples were successfully detected by the established method. The MMON-SO 3 H@SO 3 Na also exhibited good selectivity toward multiple types of polar contaminants containing hydrogen-bonding sites and aromatic structures. This work provided a new postsynthesis strategy for constructing novel and multifunctioned magnetic MONs for preconcentration of trace analytes in a complex matrix.

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (β-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-βCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-βCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.

Graphene oxide (GO) crosslinked nanocomposites hydrogels (NCH) of chitosan (CS) and carboxymethyl cellulose (CMC) were synthesized and the feasibility of its application as a versatile adsorbent for the remediation of cationic (methylene blue, MB) as well as anionic (methyl orange, MO) dyes contaminated wastewater was explored. Initially, GO was functionalized with vinyltriethoxysilane which was subsequently used as a chemical crosslinker to synthesize the NCH of CS and CMC (CS/CMC-NCH) with the polymeric mixture of diallyldimethylammonium chloride and 2-acrylamido-2-methyl-1-propanesulfonic acid. About 99% dye was adsorbed from 50 mg/L dye solution of MB dye with 0.4 g/L of CS/CMC-NCH at pH 7, whereas, for MO about 82% dye was adsorbed with 0.6 g/L of CS/CMC-NCH at pH 3. The Adsorption of both dyes is well explained using pseudo-second-order and Langmuir models with the maximum adsorption capacities of 655.98 mg dye /g ads for MB and 404.52 mg dye /g ads for MO. Thermodynamics studies suggested spontaneous and exothermic nature of the adsorption process with values of ΔS < 0 and ΔH > 0. Furthermore, CS/CMC-NCH showed excellent regeneration capacity for continuous twenty cycles of adsorption-desorption. Therefore, the synthesized CS/CMC-NCH is a versatile adsorbent that can treat both anionic and cationic dyes contaminated wastewater., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable photoprotecting groups has the potential to further expand the established utility of the photoactivation strategy in biological applications by offering higher tissue penetration, diminished phototoxicity, and compatibility with other light-dependent techniques. Nevertheless, a critical barrier to such applications remains the significant hydrophobicity of most visible-light excitable photocaging groups. Here, we find that applying the conventional 2,6-sulfonation to meso -methyl BODIPY photocages is incompatible with their photoreaction due to an increase in the excited state barrier for photorelease. We present a simple, remote sulfonation solution to BODIPY photocages that imparts water solubility and provides control over cellular permeability while retaining their favorable spectroscopic and photoreaction properties. Peripherally disulfonated BODIPY photocages are cell impermeable, making them useful for modulation of cell-surface receptors, while monosulfonated BODIPY retains the ability to cross the cellular membrane and can modulate intracellular targets. This new approach is generalizable for controlling BODIPY localization and was validated by sensitization of mammalian cells and neurons by visible-light photoactivation of signaling molecules.

In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.

Four stimuli-responsive polymers of N -isopropylacrylamide (NIPA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) and crosslinked derivatives by N,N' -methylene bisacrylamide (MBA) were synthesized: PNA, PAMPSA, PNAM, PAMPSAM. The effect of the cross-linker and methyl sulphonic acid (-CH₃-SO₃H) group on particle size, aggregation and volume phase transition temperature (VPTT) was investigated. Polymeric particles were synthesized via the surfactant free precipitation polymerization (SFPP) at 70 °C in the presence of cationic initiator 2,2'-azobis[2-methylpropionamidine] dihydrochloride (AMP) system. Chemical composition and morphology of investigated samples were evaluated using ATR-FTIR spectroscopy, ¹H-NMR spectrometry and SEM-EDS techniques. The hydrodynamic diameters (HD), zeta potential (ZP), and polydispersity index (PDI) in aqueous dispersions were assessed by dynamic light scattering (DLS) between 18⁻42 °C. HD values at 18 °C for PNA, PAMPSA, PNAM, PAMPSAM polymers were approx. 32, 730, 715, 665 nm, and ZP values were -1.36, -0.01, 8.90, -0.09 mV, respectively. The VPTT range was observed between 29 and 41 °C. PDI's for PNA and PNAM were low and varied between 0.276 and 0.460, and between 0.119 and 0.056, respectively. PAMPSA and PAMPSAM were characterized by higher PDI in the range 0.728⁻0.959 and 0.658⁻0.836, respectively. The results confirmed the thermal sensitivity of the synthesized polymers and indicated a significant polydispersity and aggregation tendency of the resulting molecules. The conductivity results were applied for the interpretation of the polymerization process.

Biliverdin (BV) possesses antioxidant and anti-inflammatory properties, with previous reports identifying protection against oxidant and inflammatory injury in animal models. Recent reports indicate that intra-duodenal administration of BV results in the formation of an uncharacterised metabolite, which is potently absorbed into the blood and excreted into the bile. This compound may be responsible for protection against inflammatory responses. This study aimed to identify novel, enterally-derived BV metabolites and determine the source of their metabolic transformation. Rat duodena and bacterial cultures of Citrobacter youngae were treated with BV and subsequently analysed via high performance liquid chromatography/high resolution tandem mass spectrometry to identify and characterise metabolites of BV. A highly abundant metabolite was detected in duodenal wash and bacterial culture supernatants with a 663.215 m/z (3 ppm mass accuracy) and a composition of C 33 N 4 O 9 H 36 S, which conformed to the predicted structure of bilirubin-10-sulfonate (BRS) and possessed a λ max of 440 nm. Bilirubin-10-sulfonate was then synthesized for comparative LCMS/MS analysis and matched with that of the biologically formed BV metabolite. This report confirms the formation of a previously undocumented metabolite of BV in mammals, indicating that a new metabolic pathway likely exists for BV metabolism requiring enteric bacteria, Citrobacter youngae. These data may have important implications with regard to understanding and harnessing the therapeutic efficacy of oral BV administration.

For soil rehabilitation, the surfactant-enhanced remediation has emerged as a promising technology. For this purpose, starch derivatives were difunctionalized by 1,4-butane sultone (BS) and 2-octen-1-ylsuccinic anhydride (OSA). Eight distinct products were obtained under different synthesis conditions. The chemical structural characteristics were investigated by (1)H NMR spectroscopy. The compounds were evaluated for their apparent aqueous solubility and their ability to increase the solubility of a hydrophobic pollutant such as benzo[a]pyrene (BaP), used as a polycyclic aromatic hydrocarbon model. In comparison with native starch, the best obtained compound increased starch apparent aqueous solubility by a factor of 10 (up to 3.50g/L) and also stimulated 77-fold BaP aqueous solubilization (up to 232.97μg/L) underlining its very high surfactant property. In this study, the right balance between hydrophobic character (octenyl succinate group (OS) grafted) of starch derivatives and starch apparent aqueous solubility (BS grafted) was highlighted., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We report a modular three-component dynamic kinetic resolution (DKR) that affords enantiomerically enriched hemiaminal esters derived from azoles and aldehydes. The novel and scalable reaction can be used to synthesize valuable substituted azoles in a regioselective manner by capping (e.g., acylation) of the equilibrating azole-aldehyde adduct. With the use of a prolinol-derived DMAP catalyst as the chiral Lewis base, the products can be obtained in high chemical yield and with high enantiomeric excess. The DKR was performed on a multikilogram scale to produce a tetrazole prodrug fragment for a leading clinical candidate that posed formidable synthesis challenges.

A self-immolative γ-aminopropylsulfonate linker was investigated for use in the development of prodrugs that are reactive to various chemical or biological stimuli. To demonstrate their utility, a leucine-conjugated prodrug of 5-chloroquinolin-8-ol (5-Cl-8-HQ), which is a potent inhibitor against aminopeptidase from Aeromonas proteolytica (AAP), was synthesized. The sulfonate prodrug was considerably stable under physiological conditions, with only enzyme-mediated hydrolysis of leucine triggering the subsequent intramolecular cyclization to simultaneously release 5-Cl-8-HQ and form γ-sultam. It was also confirmed that this γ-aminopropylsulfonate linker was applicable for prodrugs of not only 8-HQ derivatives but also other drugs bearing a phenolic hydroxy group., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Dissymmetric and symmetric anionic gemini surfactants, N-alkyl-N'-alkyl-N,N'dipropanesulfonylethylenediamine (CmCnSul, where m and n represent alkyl chain lengths of m-n = 4-16, 6-14, 8-12, 10-10, and 12-12), were synthesized by two- or three-step reactions. Their physicochemical properties were characterized by equilibrium surface tension measurements, steady-state fluorescence spectroscopy of pyrene, and dynamic light scattering. The critical micelle concentration (CMC) of the dissymmetric surfactants C4C16Sul, C6C14Sul, and C8C12Sul was slightly lower than that of the symmetric surfactant C10C10Sul. The occupied area per molecule (A) of C8C12Sul was smaller than that of C10C10Sul, indicating that C8C12Sul has a high surface activity. However, the increase in the degree of dissymmetry from C8C12Sul to C6C14Sul and then to C4C16Sul resulted in high surface tension and large A. Based on the surface tension, the standard free energies of micellization (∆G°mic) and adsorption (∆G°ads), the efficiency of surface adsorption (pC20), and the effectiveness of surface adsorption (CMC/C20) were obtained. These parameters suggested that C8C12Sul formed micelles more readily than the other surfactants. The properties determined from the surface tension indicated that C8C12Sul's ability is intermediate between those of C10C10Sul and C12C12Sul. The pyrene fluorescence and dynamic light scattering results revealed that the micelle size depends on the longer of the two alkyl chains in dissymmetric surfactants.

Superoxide anion radical (O2(•-)) is undoubtedly the most important primary reactive oxygen species (ROS) found in cells, whose formation and fate are intertwined with diverse physiological and pathological processes. Here we report a highly sensitive and selective O2(•-) detecting strategy involving O2(•-) cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We have synthesized three new O2(•-) fluorescent probes (HKSOX-1, HKSOX-1r for cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit excellent selectivity and sensitivity toward O2(•-) over a broad range of pH, strong oxidants, and abundant reductants found in cells. In confocal imaging, flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied to detect O2(•-) in multiple cellular models, such as inflammation and mitochondrial stress. Additionally, our probes can be efficiently applied to visualize O2(•-) in intact live zebrafish embryos. These probes open up exciting opportunities for unmasking the roles of O2(•-) in health and disease.

Two sulfonated resorcinarenes were synthesized by reacting C-tetra(butyl) resorcinarene or C-tetra(2-(methylthio)ethyl)resorcinarene with formaldehyde in the presence of sodium sulfite. Their structures were determined via FT-IR, 1H-NMR, 13C-NMR and mass spectrometry. Thermal gravimetric analyses of the derivatives were also carried out and revealed the presence of water molecules in the solid state. The sulfonated product of C-tetra(butyl)resorcinarene was characterized by an X-ray crystal structure determination. The asymmetric unit contains eight molecules of water and two of acetone, and analysis indicated that sulfonated resorcinarene prefers a cone configuration (rccc conformation) in the solid state. In the crystal array, classical hydrogen bond interactions O-H···O and intermolecular contacts were observed. In the crystal packing, a linear array of capsules of sulfonated resorcinarenes was generated for a chain of sodium atoms and sulfonate groups.

A series of novel cyano oximino sulfonate derivatives were prepared from the reaction of arylsulfonyl chloride with different cyanoacetamide-based oximes ranging from the simplest unsubstituted amide to analogues containing N-ethyl (mimicking the Oxyma template), N-piperidinyl and N-morpholinyl chains. In addition, the cyano oximes, N-hydroxybenzimidoyl cyanide and N-hydroxypicolinimidoyl cyanide were also used in the synthesis of the novel cyano oximino sulfonate derivatives. The structures of the prepared compounds were confirmed by (1)H-NMR, (13)C-NMR, and elemental analysis. The preliminary bioassays showed that some of the title compounds, such as 2-oxo-2-(piperidin-1-yl)-N-(tosyloxy)acetimidoyl cyanide (TsPipOx), N-(tosyloxy)benzimidoyl cyanide (TsPhOX), N-(naphthalen-2-ylsulfonyloxy)-2-oxo-2-(piperidin-1-yl)acetimidoyl cyanide (NpsPipOx), 2-amino-N-(naphthalen-2-ylsulfonyloxy)-2-oxoacetimidoyl cyanide (NpsAmOx), N-(naphthalen-2-ylsulfonyloxy)benzimidoyl cyanide (NpsPhCN), and N-(naphthalen-2-ylsulfonyloxy)picolinimidoyl cyanide (NpsPyCN), showed anti-proliferation effect on the mouse fibroblast L929. The calculated IC50-values were ranging between 36.5 µg/mL and 0.235 mg/mL. However the anti-proliferation effects seem to be cytostatic rather than cytotoxic. The compounds only minimize the growth activity without completely killing the cells.

Sulfonated carbonaceous material useful as a solid acid catalyst was prepared from lignosulfonate, a waste of the paper-making industry sulfite pulping process, and characterized by 13C-NMR, FT-IR, TGA, SEM and elemental analysis, etc. The sulfonic acid group density and total density of all acid groups in the sulfonated carbonaceous material was determined by titration to be 1.24 mmol/g and 5.90 mmol/g, respectively. Its catalytic activity in the esterification of cyclohexanecarboxylic acid with anhydrous ethanol was shown to be comparable to that of the ionic exchange resin Amberlyst-15, when they were used in the same amount. In the meantime, the sulfonic acid group was found to be leached out by 26%-29% after it was exposed to hot water (95 °C) for 5 h. The catalytic usefulness of the prepared carbonaceous material was investigated by performing esterifications.

An unusual NaH-mediated remote anionic 1,5-thia-Fries rearrangement reaction was developed. This method provides an efficient approach for the regioselective synthesis of not only 2-(2-hydroxyphenyl)-3-indole triflones but also related 3-sulfonylindoles.

Synthetic hydrogel polymers were prepared by free radical photopolymerization in aqueous solution of the sodium salt of 2-acrylamido-2-methylpropane sulfonic acid (Na-AMPS). Poly(ethylene glycol) diacrylate (PEGDA) and 4,4'-azo-bis(4-cyanopentanoic acid) were used as the crosslinker and UV-photoinitiator, respectively. The effects of varying the Na-AMPS monomer concentration within the range of 30-50% w/v and the crosslinker concentration within the range of 0.1-1.0% mol (relative to monomer) were studied in terms of their influence on water absorption properties. The hydrogel sheets exhibited extremely high swelling capacities in aqueous media which were dependent on monomer concentration, crosslink density, and the ionic strength and composition of the immersion medium. The effects of varying the number-average molecular weight of the PEGDA crosslinker from [Formula: see text] = 250 to 700 were also investigated. Interestingly, it was found that increasing the molecular weight and therefore the crosslink length at constant crosslink density decreased both the rate of water absorption and the equilibrium water content. Cytotoxicity testing by the direct contact method with mouse fibroblast L929 cells indicated that the synthesized hydrogels were nontoxic. On the basis of these results, it is considered that photopolymerized Na-AMPS hydrogels crosslinked with PEGDA show considerable potential for biomedical use as dressings for partial thickness burns. This paper describes some structural effects which are relevant to their design as biomaterials for this particular application.

A superabsorbent composite (alginate-g-PAMPS/MMT) was prepared by graft copolymerization from alginate, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and Na+ montmorillonite (MMT) in an inert atmosphere. Effects of polymerization variables on water absorbency, including the content of Na+ montmorillonite, sodium alginate, N,N'-methylenebisacrylamide and AMPS, were studied. The introduced montmorillonite formed a loose and porous surface and improved the water absorbency of the alginate-g-PAMPS/MMT superabsorbent composite. Swelling behaviors of the superabsorbent composites in various cationic salt solutions (NaCl, CaCl2 and FeCl3) and anionic salt solutions (NaCl and Na2SO4) were also systematically investigated. The superabsorbent composite was further characterized using Fourier transform infrared spectroscopy (FTIR), rheology, thermogravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM) taking alginate-g-PAMPS as a reference., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

An anionic fluorene-phenylene poly{1,4-phenylene-[9,9-bis(4-phenoxy-butylsulfonate)]fluorene-2,7-diyl}-based copolymer containing on-chain perylenediimine (PDI) chromophoric units, PBS-PFP-PDI, was synthesized and its photophysical properties studied as aggregates and isolated chains in water and dioxane/water (1:1) solution. UV-vis and emission spectroscopy measurements, time-correlated single photon counting, and wide field imaging have been employed to investigate the excited-state behavior of the PBS-PFP-PDI copolymer, including the effect of environment on the energy and electron transfer to the on-chain PDI chromophore. Although the Förster overlap integral is favorable, no evidence is found for intramolecular singlet excitation energy transfer in isolated copolymer chains in solution. Fluorescence is suggested to involve an interchain process, thus revealing that isolated copolymer chains in solution do not undergo efficient intramolecular energy transfer. However, quenching of the PBS-PFP excited state by PDI is observed in aqueous media and ultrafast pump-probe studies in water or dioxane-water solutions show that electron transfer occurs from the phenylene-fluorene units to the PDI. The extent of electron transfer increases with aggregation, suggesting it is largely an interchain process. The interaction of the negatively charged PBS-PFP-PDI copolymer with the positively charged surfactant hexadecyltrimethylammonium bromide (CTAB) in solution has also been studied. The copolymer PBS-PFP-PDI aggregates with the surfactant already at concentrations below the critical micelle concentration (cmc) and the nonpolar environment allows intermolecular energy transfer, observed by the weak emission band located at 630 nm that is associated with the emission of the PDI chromophore. However, the fact that the PDI photoluminescence (PL) lifetime (~1.4 ns) obtained in the presence of CTAB is considerably shorter than that of the nonaggregated chromophore (~5.4 ns) suggests that even in this case there is considerable PL quenching, possibly through some charge transfer route. The increase of the PBS-PFP-PDI photoluminescence intensity at surfactant concentrations above the cmc indicates deaggregation of polyelectrolyte within the initially formed polyelectrolyte-surfactant aggregates.

A series of 3-substituted (5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl sulfonate (nitroCBI) prodrugs containing sulfonate leaving groups undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents. They were evaluated (along with chloride leaving group analogs for comparison) for their cytotoxicity against cultures of SKOV3 and HT29 human tumor cell lines under both aerobic and hypoxic conditions. Sulfonates with neutral side chains (e.g., 5,6,7-trimethoxyindole; TMI) show consistently higher hypoxic cytotoxicity ratios (HCRs) (34-246) than the corresponding chloro analogs (2.8-3.1) in SKOV3 cells, but these trends do not hold for compounds with cationic or polar neutral side chains., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The insertion reaction of diazocarbonyls to acids could be performed smoothly in fluorinated alcohols in the absence of metal catalyst. This new procedure allowed the chemoselective preparation of various functionalized compounds such as acyloxyesters, depsipeptides, and sulfonate, phosphonate, or boronate derivatives.

Photochemical bond-cleavage reactions are potentially useful in chemistry, bioorganic chemistry and medicinal chemistry. We previously reported on a photochemical cleavage reaction of 8-quinolinyl sulfonate (8-QS) derivatives in aqueous solution at neutral pH, which we proposed to proceed via an excited triplet state. In this report, we report on the synthesis of some new photocleavable 8-QS derivatives, in which halogen atoms or a nitro group was introduced at the 7-position, in an attempt to improve photoreactive properties and to produce a red-shift in the irradiation wavelength. The introduction of bromine and iodine resulted in an acceleration in the photoreaction by about 1.5 times, possibly due to a heavy atom effect. It was also found that 7-nitro-8-QS absorbs at >360 nm, and, as a result, the S-O bond of this compound can be cleaved by photoirradiation with a fluorescent lamp in aqueous solution and on silicon surface.

alpha-Methyl esters sulfonates (alpha-MES) are anionic surfactants that are derived from biorenewable resources, offering interesting environmental and chemical properties for application in the detergent industry. A simulation of their production process was conducted using a commercial production process currently used for palm oil. Results, prices of raw materials were submitted to economic analysis, and final MES price was compared with available data for linear alkyl benzene sulfonates (LAS) prices. The results for substances properties and product streams obtained from simulation were reliable in agreement to real values. It was found that increasing methyl ester national price by 20%, 50% and the equivalent to linear alkyl benzene price, the final price of alpha-methyl ester sulfonates was lower than the current price of linear alkyl benzene sulfonates. The capital cost and payout period for a production capacity of 49,000tons of surfactant per year were obtained. Results indicate that the process is economically feasible and can be applied to palm oil-based industries in Colombia.

The synthesis of the polymerizable fluorinated surfactant sodium 1,1,2,2-tetrafluoro-2-(1,1,2,2-tetrafluoro-2-(4-vinylphenyl)ethoxy)ethanesulfonate (1) and a number of related fluorocarbon compounds is described. Compound 1 is synthesized using a copper-mediated cross-coupling reaction of 4-bromobenzaldehyde and sodium 5-iodooctafluoro-3-oxapentanesulfonate. The resulting benzaldehyde is converted to a styrene unit using a Wittig reaction with methyltriphenylphosphonium bromide in acetonitrile, using DBU as a base. This strategy for converting an iodo-functionalized fluorosurfactant to a styrene-containing fluorosurfactant is highly efficient because both reactions are performed in polar solvents and are compatible with the sulfonate moiety. In addition, the copper-mediated cross-coupling reaction is most efficient with electron-poor aryl bromides like 4-bromobenzaldehyde. We wish to employ 1 for the construction of nanostructured membranes by polymerization of 1 in a microemulsion or in lyotropic liquid crystalline phases.

Employment of heteroaromatic tosylates and phosphates as suitable electrophiles in iron-catalyzed cross-coupling reactions with alkyl Grignard reagents is reported. These reactions are performed at low temperature allowing good functional group tolerance and full conversion is achieved within minutes. In addition, an aryl-aryl cross-coupling utilizing a heteroaryl sulfamate electrophile is reported.

A set of 1-alkyl-3-methylimidazolium alkanesulfonate ionic liquids, [C(n)mim][C(k)SO(3)], formed by the variation of the alkyl chain lengths both in the cation and the anion (n = 1-6, 8, or 10; k = 1-4, or 6), was synthesised, with sixteen of them being novel. The ionic liquids were characterised by (1)H and (13)C NMR spectroscopy, and mass spectrometry. Their viscosities and densities as a function of temperature, as well as melting points and decomposition temperatures, were determined. The molecular volumes, both experimental and calculated, were found to depend linearly on the sum (n + k).

The number of reports on new techniques in molecular imaging has been recently increasing because of their usefulness in biological, medical, and clinical research. Fluorescence imaging methods are generally superior in terms of sensitivity, selectivity and ease of use. Cyanine dyes have been employed as fluorescent labels in fluorescence imaging studies of biological mechanisms. In particular, tricarbocyanines have the advantage that light at their emission and absorption maxima in the near-infrared (NIR) region around 650-900 nm is relatively poorly absorbed by biomolecules, and so can penetrate deeply into tissues. There is also less autofluorescence in this region. In addition to cyanine dyes for straightforward fluorescence labeling, we successfully developed cyanine dyes whose fluorescence intensity changes upon specific reaction with nitric oxide, which is an important signaling molecule involved in the regulation of a wide range of physiological and pathophysiological mechanisms, and many disorders. Then, we synthesized dipicolylcyanine (DIPCY), consisting of tricarbocyanine as a fluorophore and dipicolylethylenediamine as a heavy metal chelator, and investigated its response to various heavy metal ions. Upon addition of zinc ion, a red shift of the absorbance maximum was observed. Namely, DIPCY can work as a ratiometric fluorescent sensor for zinc ion in the NIR region. Moreover, we have recently developed several pH probes based on the amine-substituted tricarbocyanine fluorophore. We could measure pH with these fluorescent probes by a ratiometric monitoring method.

We identified a series of 2-phenyl-ethenesulfonic acid phenyl ester analogues as novel dual-function agents that suppressed nitric oxide production in lipopolysaccharide/interferon gamma-stimulated RAW264.7 cells and activated peroxisome proliferator-activated receptor gamma (PPARgamma) in a cell-based transactivation assay. Western blot analysis demonstrated that these compounds inhibit the expression of inducible nitric oxide synthase protein, and scintillation proximity assay validated their ability to bind to PPARgamma. Our studies provide the basis for developing these dual-function agents for anti-inflammation and anti-atherosclerosis therapy.

The appropriately substituted 5-O-tosyl derivative (1), easily prepared from 1,2-O-isopropylidene-alpha-d-xylofuranose, serves as a useful precursor for the preparation of highly condensed cyclic carbohydrates. The synthesis involves a first cyclization of the 5-O-tosyl sugar derivative 1 to a highly reactive cyclic enamine, which subsequently undergoes the nucleophilic attack of a bifunctional reagent X(CH2)nZ in a regio- and stereospecific way. Finally, a spontaneous cyclization step allows the formation of a stereochemically defined extra ring, fused to the sugar backbone. The functionalization and size of this ring can be varied by the proper choice of the bifunctional reagent. X-ray diffraction analysis and intensive NMR studies with one of these carbohydrates were performed to highlight the strained nature of these compounds.

The first member of a novel class of chemoselective reagents, glycosyl methanedithiosulfonates, has been synthesized, identified and employed in the first examples of chemical, site-selective construction of a trisulfide-modified protein with complete conversion.

A novel water-soluble solvatochromic molecule, 7-(dimethylamino)-2-fluorenesulfonate (2,7-DAFS), was prepared by a three-step reaction from 2-nitrofluorene in good overall yield. The pH and solvent effects on the UV-VIS absorption and fluorescence spectra of 2,7-DAFS have been studied. Protonation of the dimethylamino group switches the absorption from intramolecular charge-transfer (ICT) to pi --> pi* transition. The ground state pKa value of 2,7-DAFS was determined as 4.51. The fluorescence spectrum of the excited basic form, *(DAFS), shows a structureless single band with a large Stokes shift, whereas that of the acidic form, *((+)HDAFS), exhibits a structured band with a small Stokes shift. The emission intensities of the basic and acidic forms versus pH/Ho plots show stretched sigmoidal curves and indicate that (1) the rate of deprotonation of *((+)HDAFS) is comparable to the fluorescence decay of the species, and (2) the efficient proton-induced quenching of *(DAFS) fluorescence occurs. The pKa* was estimated as -1.7 from the fluorescence titration curve. The fluorescence maximum of *(DAFS) is blue-shifted as the polarity of solvent decreases. However, no clear dependency of the emission intensity and spectral half width, and thus fluorescence quantum yield, on the solvent polarity was revealed. It appears that the fluorescence sensitivity of 2,7-DAFS is 15 approximately 25 times greater than the sensitivity of a widely utilized fluorescent probe, 5-(dimethylamino)-1-naphthalenesulfonate. This higher sensitivity, together with the ease of derivatization, would provide the fluorene-based fluorescent molecules significant advantages for a variety of applications.

Paeoniflorin is one of the bioactive ingredients of the roots of Paeonia lactiflora (Paeoniaceae). A comparative study of processed and non-processed commercial samples of dried roots of P. lactiflora indicated a very low level of paeoniflorin in the processed sample and the formation of a new more polar component, sodium paeoniflorin sulphonate, during treatment of the roots with sulphiting agents.

AstraZeneca plc is developing tesaglitazar, an oral dual peroxisome proliferator-activated receptor alpha/gamma agonist, for the potential improvement of dyslipidemia and glycemic control in type 2 diabetic patients.

The thermotropic polymorphism of a series of guanidinium alkanesulfonates (6 < or = n < or = 18) was investigated by optical microscopy and differential scanning calorimetry. Hydrogen bonding was analyzed by infrared spectroscopy. Molecular volumes were measured by dilatometry. The structure of the crystal, smectic A, and ordered smectic phases observed were studied by X-ray diffraction and utilized to prove that the supramolecular arrangement of the molecules in the crystal survives in the smectic phases at high temperature.

The replacement of peptide bond is an important segment in the synthesis of peptidomimetics, because this modification may result in the preparation of biologically active analogues with improved properties, especially regarding bioavailability and metabolical stability. The introduction of sulfonamide group increases polarity of a molecule and the hydrogen-bond donor properties as a sulfonamide N-H is more acidic (pKa=11-12) than carboxamide. Furthermore, due to geometry of sulfur atom the sulfonamido bond shows structural similarity to the tetrahedral transition state present as an intermediate in the enzymatic hydrolysis of an amide bond thus making these compounds candidates in the development of new drugs. Recent advances in the synthesis of building blocks for sulfonamidopeptides, such as alpha or beta- substituted aminoalkylsulfonates and efficient methods for the formation of sulfonamide bond have enabled the preparation of large number of oligomers with potential applications on various fields. These methods have been applied for the synthesis of oligopeptidosulfonamides, catalysts, receptor molecules and enzyme inhibitors. This article deals with physicochemical properties of sulfonamides, synthesis of aminoalkylsulfonates and sulfonamidopeptides, and the biological activity of these compounds.

A method for the generation of soluble glycosphingolipid derivatives that retain the receptor activity of the parent (BBRC 257:391-394, Carb Res 335:91-100) was used to investigate the consequence of 3'sulfogalactolipid (SGL) specific binding within the N-terminal ATPase-containing domain of Hsc70. Sulfogalactosyl ceramide (SGC) was deacylated, and the resulting sulfogalactosylsphingosine coupled to an alpha-adamantane or a norbornane rigid hydrophobic frame. The resulting conjugate preferentially partitioned into water, as opposed to organic solvent. In the range of 100-300 microM, these conjugates inhibited the specific binding of bovine brain Hsc70 to immobilized SGLs. A similar dose-related inhibition of bovine brain Hsc70 ATPase activity was seen between 100 and 300 microM adamantylSGC (adaSGC). Adamantyl conjugates of glycolipids not bound by Hsp70s had no effect. Kinetic analysis indicated that adaSGC was a noncompetitive inhibitor of Hsc70 ATPase activity, a special case of mixed inhibition since the K(m) values were not statistically different, 0.89 +/- 0.024 microM to 0.93 +/- 0.038 microM, but the V(max) decreased from 0.20 +/- 0.012 pmol min(-1) microg(-1) to 0.15 +/- 0.016 pmol min(-1) microg(-1). A reproducible 5 min lag was observed prior to ATPase inhibition that could be eliminated by preincubation of adaSGC with Hsc70 or by adding the cochaperone Hdj-1. The dependence of ATPase inhibition on the rate of hydrolysis indicates that adaSGC binding occurs at a specific stage of the ATPase cycle. These studies identify a new mechanism for the regulation of Hsp70 ATPase activity.

We report the facile preparation of O2-sulfonated diazeniumdiolates and mechanistic investigation of their reactions with representative nucleophiles. This new class of compounds extends the range of O2-substituted diazeniumdiolates available for potential applications in research and medicine.

Two new compounds, sodium N-(6, '8-dimercaptooctanoyl)-2-amino ethanesulfonate- and sodium N-(6, 8-dimercaptooctanoyl)-L-aspartate - zinc complex were synthesized from alpha-lipoyl-2-aminoethanesulfonate and alpha-lipoyl-L- aspartate by reduction of zinc/acetic acid respectively. These alpha-lipoyl-amino acids were obtained by a coupling of alpha-lipoic acid and 2-aminoethanesulfonate or L-aspartate, using a mixed anhydride method. Scavenging activities of these derivatives against hydroxyl radicals (*OH) was demonstrated directly using electron spin resonance (ESR) spectrometry with spin trapping. Otherwise an apparent superoxide anion radical (O2*-) scavenging effect of these derivatives may be due to the inhibition of 02*- generation system, i.e., xanthine oxidase. Scavenging activities of these compounds against nitric oxide radicals (NO*), and peroxynitrite (ONOO-) were estimated by the flow injection analysis using the Griess reagent and by a fluorescence spectrometry using dihydrorhodamine 123 respectively. Meanwhile, these derivatives showed protective effects against lipid peroxidation and protein carbonyl formation. Scavenging activities against NO* and ONOO-, and inhibitory effects on protein carbonyl formation of these derivatives were much stronger than these of alpha-lipoic acid itself.

In the previous paper, we described a series of 2-phenylethenesulfonamide derivatives, a novel class of ET(A)-selective endothelin (ET) receptor antagonists, including the 2-methoxyethoxy derivative 2a and the 2-fluoroethoxy derivative (2b). In this paper, we wish to report further details of structure-activity relationships (SARs) of the two regions of the molecule in compound 2b, which were the alkoxy region at the 6-position of the core pyrimidine ring and the 2-phenylethenesulfonamide region. In these modifications, replacement of the 2-fluoroethoxy group with a methoxy group (6e) and replacement of the 2-phenylethenesulfonamide group with a 2-(pyridin-3-yl)ethenesulfonamide group (6l) or 2-phenylethanesulfonamide group (6q) were well tolerated both in the ET(A) binding affinity and ET(A) selectivity. Among them, compound 6e showed further improvement in oral activity compared to 2b. After oral administration, compound 6e inhibited the big ET-1 induced pressor response in conscious rats at 0.3mg /kg with a duration of >6.5h. Compound 6e also exhibited a potent antagonistic activity in the pithed rats.

A number of alkanesulfonyl halides (chlorides and fluorides) and esters were synthesized and their effect on the activity of lipoprotein lipase (LPL) was studied. Sulfonyl fluorides proved to be efficient inhibitors of LPL when the enzyme was incubated with a 10-fold molar excess of the inhibitors in a buffer containing bile salts (deoxycholate). Hexadecane- and dodecanesulfonyl fluorides caused 50% inhibition of LPL activity at concentrations of 10 to 20 microM.

[reaction: see text] Reactions of steroidal alpha,beta-epoxy vinyl triflates in Pd-catalyzed reactions are described. Oxidative insertion of Pd(0) into the C-O bond, giving vinylpalladium 12, is faster than formation of the pi-allyl derivative from the vinyl epoxide. Although 12 can be trapped under certain conditions, it eventually rearranges to palladium alkoxide 14, which is in equilibrium with 15 and/or 10.

Aryl/alkyl-sulfonyl-, aryl/alkylcarboxyl- and aryl(sulfonyl)carbamyl/thiocarbamyl-derivatives of dibenzo-1,4-dioxine-2-acetyloxime were prepared by reaction of the title compound with sulfonyl halides, sulfonic acid anhydrides, acyl chlorides/carboxylic acids, arylsulfonyl isocyanates, aryl/acyl isocyanates or isothiocyanates. Several of the newly synthesized compounds showed effective in vitro antifungal activity against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole (with minimum inhibitory concentrations in the range of 1.2-4 microg/mL) against the two Aspergillus strains, but possessing a lower activity as compared to ketoconazole against C. albicans. Of the three investigated strains, best activity was detected against A. flavus. The mechanism of action of these compounds probably involves inhibition of ergosterol biosynthesis by interaction with lanosterol-14-alpha-demethylase (CYP51A1), since reduced amounts of ergosterol were found by means of HPLC, in cultures of the sensitive strain A. flavus treated with some of these inhibitors. Thus, the compounds reported here might possess a similar mechanism of action at molecular level with that of the widely used azole antifungals.

Amyloid is a term for extracellular protein fibril deposits that have characteristic tinctorial and structural properties. Heparan sulphate, or the heparan sulphate proteoglycan perlecan, has been identified in all amyloids and implicated in the earliest stages of inflammation-associated (AA) amyloid induction. Heparan sulphate interacts with the AA amyloid precursor and the beta-peptide of Alzheimer's amyloid, imparting characteristic secondary and tertiary amyloid structural features. These observations suggest that molecules that interfere with this interaction may prevent or arrest amyloidogenesis. We synthesized low-molecular-weight (135-1,000) anionic sulphonate or sulphate compounds. When administered orally, these compounds substantially reduced murine splenic AA amyloid progression. They also interfered with heparan sulphate-stimulated beta-peptide fibril aggregation in vitro.

The ability of 3-hydroxypyrid-4-ones bearing either a carboxylic acid or sulfonic acid group to mobilize iron into the bile and urine of normal rats has been examined and compared with that produced by 1,2-dimethyl-3-hydroxypyrid-4-one (L1). The compounds tested were 3-hydroxy-1-methyl-4-oxopyridine-6-carboxylic acid and 1-[3-hydroxy-6-(hydroxymethyl)-4-oxopyridyl]-2-ethanesulfonic acid, whose synthesis, biological activity, and X-ray crystallographic properties are described. Although estimates of activity, based on polarity and membrane permeability, predict such compounds to be ineffective, they were found to have an iron-mobilizing ability similar to that of the compounds which do not bear any charge at physiological pH when given parenterally. When given orally, the 3-hydroxypyrid-4-one containing a carboxylate group enhanced the urinary excretion of iron, while the sulfonate analog did not substantially increase the excretion of iron in the urine relative to the controls. The results obtained here suggest that the previous emphasis on the preparation of 3-hydroxypyrid-4-ones that are electrically neutral at physiological pH is unnecessarily restrictive and that the presence of an appropriate group bearing a single negative charge is consistent with a high level of activity. It is proposed that such negatively charged molecules may gain access to the interior of cells in both the kidney and the liver via monoanionic transport systems. Such compounds may prove to be less toxic than the neutral 3-hydroxypyrid-4-ones.

A series of sulfonate esters that are attached to a noncationic minor-groove-binding N-methylpyrrole dipeptide (Lex) related to netrospin have been synthesized. The compounds prepared differ in two respects: (1) the length [(CH2)2 vs (CH2)8] of the tether between the DNA affinity binding portion of the molecule and the sulfonate ester and (2) whether a methyl group [MeOSO2(CH2)n-Lex] or the dipeptide including the aliphatic tether [MeSO2O(CH2)n-Lex] is covalently transferred to the DNA. The DNA-cleavage patterns of these bimolecular alkylating compounds have been mapped in 32P-end-labeled restriction fragments using neutral thermal hydrolysis and alkali treatment to expose single-strand breaks at bases with thermally labile modifications. In contrast to the alkylation of DNA by simple alkyl alkanesulfonate esters, that predominantly yield major-groove alkylation at N7-guanine, the modification of DNA by MeOSO2(CH2)n-Lex and MeSO2O(CH2)n-Lex occurs primarily at N3-adenine residues associated with previously footprinted Lex DNA affinity binding regions. The ratio for the formation of N3-methyladenine (minor groove) to N7-methylguanine (major groove) in calf thymus DNA is 1:7 for dimethyl sulfate, while only the former adenine product is observed with MeSO2O(CH2)n-Lex indicating the change in groove specificity. DNA cleavage by MeOSO2(CH2)n-Lex and MeSO2O(CH2)n-Lex is efficiently inhibited by the coaddition of distamycin; however, only the DNA damage generated by the latter is blocked by NaCl. As expected, increasing the length of the (CH2)n tether from n = 2 to n = 8 moves the alkylation site by 1-2 base pairs further from the affinity binding domain. Finally, a comparison of the methylation patterns of MeOSO2(CH2)n-Lex as a function of tether length provides an insight into Lex sequence and orientational preferences.

New hydrophilic alkylating agents, isethionic acid esters, are proposed for use as synthetic biological alkylating agents. Methyl, ethyl, and isopropyl esters of isethionic acid were synthesized starting from isethionate and the corresponding alkyl bromides or iodides in good yields. This synthetic procedure might be generally applicable to syntheses of alkyl isethionates. The derivatives thus prepared were water-soluble, as expected, and their alkylating abilities were very similar to those of the corresponding methanesulfonates. Hence, isethinonic acid esters might be suitable for use as hydrophilic biological alkylating agents in place of methanesulfonates. In order to determine the effectiveness of isethionates as anticancer alkylating agents, 1,4-butanediol diisethionate was prepared as a model compound and its anticancer activities against adenocarcinoma 755, sarcoma 180, L1210, and P388 were compared with those of the corresponding methanesulfonate, busulfan. The isethionate was superior to busulfan in all the assay systems employed. 1,5-Pentanediol diisethionate was also prepared and assayed. The results were similar to those for the 1,4-butanediol analog. In conclusion, in the design of molecules for use as cancer chemotherapeutics, the isethionic acid ester group is worth considering, and may be preferable to other commonly used leaving groups, including methanesulfonic acid ester.

Homologous dialkanesulfonic esters of 2,2'-iminodiethanol, 3,3'-iminodi-1-propanol, N-(2-hydroxyethyl)-6-amino-1-hexanol, and N-(3-hydroxypropyl)-6-amino-1-hexanol were prepared via the N-trityl derivatives and screened for L1210 activity. For each active agent significant increases in life-span in L1210 tests (ILS) were correlated by linear least-squares regression with the corresponding log doses. The maximum ILS, taken from this regression line at the determined LD10, was used as a quantitative measure of antileukemic effectivenss. Within each homologoud series log ILSmax could be correlated with a binomial expression in lipophilic-hydrophilic balance, as measured by Rm values, but all active members from the four series could not be successfully included in a single correlation. By modification of Rm values with an ionization factor, log (H+/H+ + Ka), all active compounds could then be included in a significant correlation equation.