Formation Of Stoichiometric Complex Research Articles

MOSR and NDHA Genes Comprising G-Quadruplex as Promising Therapeutic Targets against Mycobacterium tuberculosis: Molecular Recognition by Mitoxantrone Suppresses Replication and Gene Regulation.

Occurrence of non-canonical G-quadruplex (G4) DNA structures in the genome have been recognized as key factors in gene regulation and several other cellular processes. The mosR and ndhA genes involved in pathways of oxidation sensing regulation and ATP generation, respectively, make Mycobacterium tuberculosis (Mtb) bacteria responsible for oxidative stress inside host macrophage cells. Circular Dichroism spectra demonstrate stable hybrid G4 DNA conformations of mosR/ndhA DNA sequences. Real-time binding of mitoxantrone to G4 DNA with an affinity constant ~105-107 M-1, leads to hypochromism with a red shift of ~18 nm, followed by hyperchromism in the absorption spectra. The corresponding fluorescence is quenched with a red shift ~15 nm followed by an increase in intensity. A change in conformation of the G4 DNA accompanies the formation of multiple stoichiometric complexes with a dual binding mode. The external binding of mitoxantrone with a partial stacking with G-quartets and/or groove binding induces significant thermal stabilization, ~20-29 °C in ndhA/mosR G4 DNA. The interaction leads to a two/four-fold downregulation of transcriptomes of mosR/ndhA genes apart from the suppression of DNA replication by Taq polymerase enzyme, establishing the role of mitoxantrone in targeting G4 DNA, as an alternate strategy for effective anti-tuberculosis action in view of deadly multi-drug resistant tuberculosis disease causing bacterial strains t that arise from existing therapeutic treatments.

Exploring the potential of quercetin/aspirin-loaded chitosan nanoparticles coated with Eudragit L100 in the treatment of induced-colorectal cancer in rats.

Growing evidence suggests quercetin and aspirin may have anticancer properties, notably in the case of colorectal cancer. The goal of this study was to create Pluronic F127 and polyethylene glycol4000 solid dispersion-loaded chitosan nanoparticles for colonic quercetin and aspirin delivery. In 1:1 polymeric stoichiometric ratio, solubility and complex formation were verified. Solid dispersion-loaded chitosan nanoparticles with a diameter of 244.45 ± 8.5nm, a surface charge of 34.1 ± 3.3mV, and encapsulation effectiveness of 76.3 ± 4.3% were generated under ideal conditions. In some cases, coating with Eudragit L100 resulted in a decrease in zeta potential and an increase in particle size. The coated formulation released the actives in a pH-dependent manner, considering their physicochemical features. Surprisingly, when compared to the actives' suspension and uncoated formulation, the coated formulation had greater anti-inflammatory efficacy, with a substantial reduction of PGE2 and IL-8 production in colonic tissues (16.9 ± 7.9ng/g tissue and 134.9 ± 10.1pg/g tissue, respectively). It also reversed most of the dimethyl hydrazine-induced histological alterations in the colon. It also demonstrated a greater reduction in TNF expression in colonic tissues. As a result, Eudragit L100-coated QT/AS-loaded chitosan nanoparticles are suggested to provide a potential platform for colonic delivery of quercetin and aspirin.

Oligo-DNA Stoichiometrically Binds β-1,3-Glucan with the Best Fit Length.

Oligo-deoxyadenylic acid (dAX) forms a novel 1:2 triple-helix with β-1,3-d-glucan schizophyllan (SPG). We found that dAX meticulously selects the most suitable length of SPG to bind; for example, dA30 only complexes with a short SPG chain having 30, 60, or 90 main-chain glucoses, and they can be easily isolated with each other. This study demonstrated such a novel stoichiometric complex formation by using gel permeation chromatography coupled with multi-angle light scattering and synchrotron small-angle X-ray scattering. These oligo-DNA/polysaccharide complexes can be used as a tool for delivering therapeutic oligonucleotides to immunocytes that express the β-1,3-d-glucan receptors. The present study provides a robust platform technique to characterize them in terms of modern regulatory science of nanomedicines, which is requisite to transfer drug candidates into clinical trial. Our findings are important for characterizing these complexes as well as for providing a new insight into nucleotide and saccharide chemistry.

Exploring the Structure and Stability of Cholesterol Dimer Formation in Multicomponent Lipid Bilayers

For 40 years, the existence and possible functional importance of cholesterol dimer formation has been discussed. Due to challenges associated with structural studies of membrane lipids, there has as yet been no direct experimental verification of the existence and relevance of the cholesterol dimer. Building on recent advances in lipid force fields for molecular simulation, in this work the structure and stability of the cholesterol dimer is characterized in POPC bilayers in absence and presence of sphingomyelin. The cholesterol dimer structural ensemble is found to consist of sub-states that reflect, but also differ from, previously proposed dimer structures. While face-to-face dimer structures predominate, no evidence is found for the existence of tail-to-tail dimers in POPC lipid bilayers. Near stoichiometric complex formation of cholesterol with sphingomyelin is found to effect cholesterol dimer structure without impacting population. Comparison with NMR-derived order parameters provide validation for the simulation model employed and conclusions drawn related to the structure and stability of cholesterol dimers in multicomponent lipid bilayers. © 2016 Wiley Periodicals, Inc.

INTERPOLYELECTROLYTE COMPLEXATION OF SULFONATE-CONTAINING AROMATIC POLY- AND COPOLYAMIDES IN ORGANIC AND AQUEOUS-ORGANIC MEDIA

Complex formation of sulfonate-containing aromatic poly- and copolyamides with copolymers of acrylonitrile with N,N-dimethyl-N,N-diallylammonium chloride and N,N-diethylaminoethyl methacrylate was studied in organic and aqueous-organic media. The values of conversion degree for interpolymer reactions were determined. At optimal conditions in the presence of poly-4,4'-(2-sodium sulfonate)diphenylaminoisophthalamide and poly-4,4'-(2-sodium sulfonate)diphenylaminoterephthalamide the degree of conversion was equal to ~0.80 and 0.78, respectively. The reduction of number of sulfonate containing units in the polymer chain to 10% leads to its decrease to ~0.18. It was shown that the nature and composition of the solvent affects the kinetics of interpolymer reactions due to the different ratio of reaggregation during the interacting of function groups in water medium with considerable force of hydrophobic interactions and in organic solvent where these forces dramatically reduce. The phase state and the composition of formed interpolyelectrolyte complexes depends on charge density along macromolecule chain of copolyamide and on the composition of the solvent used. The reduction of the number of sulfonate containing units in the macromolecule leads to polycation component increase in the complex. The formation of stoichiometric interpoly-electrolyte complexes takes place in the solvent with the same composition as that when the most significant unfolding of the polyanion chain was observed. The phase separation during the complex formation by the interpolymer reaction with copolyamide containing 5% of units with sulfonate groups or copolymer of acrylonitrile with N,N-diethylaminoethyl methacrylate is not observed.

Ultra-Bright Rhodamines with Sulfobutylether-β-Cyclodextrin: A Viable Supramolecular Dye Laser in Aqueous Medium.

Although aqueous dye lasers are much sought after, they have been of no practical use, as laser dyes show a strong tendency for aggregation in water, thus diminishing their optical output. Contributing towards this shortcoming, we studied the noncovalent interactions of two prominent laser dyes, namely, rhodamine 6G and rhodamine B, with a water soluble macrocyclic host, sulfobutylether-β-cyclodextrin (SBE7 βCD). Spectral changes in the absorption and fluorescence behavior of dyes in presence of the SBE7 βCD host indicated adequate complex formation between dye and host (K∼104 M-1 ). A combination of various photophysical parameters evaluated from measurements such as Job plot, changes in the fluorescence lifetime/anisotropy values, and favorable thermodynamic parameters from isothermal titration calorimetric measurements adjudicated a 1 : 1 stoichiometric complex formation between dye and SBE7 βCD host. Consequently, SBE7 βCD prevents dye aggregation/adsorption and present rhodamine dyes in their monomeric forms with enhanced fluorescence yield and brightness. These vital parameters were utilized to optimize and demonstrate cost-effective supramolecular broad-band and narrow-band aqueous dye laser systems with improved lasing efficiencies (∼25 % higher for the SBE7 βCD : RhB system and ∼10 % higher for SBE7 βCD : Rh6G system), better beam profile, and enhanced durability compared to the respective dyes in optically matched ethanol solutions.

Highly efficient, catalyst‐free, one‐pot, pseudo five‐component synthesis of novel pyrazoline‐containing Schiff bases, metal complexes formation and computational studies via DFT method

In this study, a green and high yielding synthesis of novel pyrazoline‐containing Schiff bases via a one‐pot pseudo five‐component condensation reaction under catalyst‐free conditions in EtOH at room temperature is described. Initially, the reaction of 1,1‐bis(methylthio)‐2‐nitroethylene (BMTNE), with NH2NH2.H2O is used for situ preparation of 1,1‐dihydrazino‐2‐nitroethylene (DHNE). Then, wide varieties of aldehydes are added to the mixture to afford the desired products good to excellent yields. This synthetic route is presented with several unique merits such as simplicity in operation and workup, readily presented starting materials, and high functional group tolerance. Additionally, the stoichiometric complex formation of these Schiff bases as ligand (L) with various metal ions [Mn(OAc)2, Cu(OAc)2 and Zn(OAc)2] in general molecular formula [ML] is examined via Job's method. Subsequently, theoretical analysis of the product is accomplished using density functional theory (DFT) calculations. According to the frontier molecular orbital (FMO) analysis, it is found that the aryl group linked to the imine bond contributes as an electron donor in the ligand–metal complex.

PH-Induced Association and Dissociation of Intermolecular Complexes Formed by Hydrogen Bonding between Diblock Copolymers.

Poly(sodium styrenesulfonate)–block–poly(acrylic acid) (PNaSS–b–PAA) and poly(sodium styrenesulfonate)–block–poly(N-isopropylacrylamide) (PNaSS–b–PNIPAM) were prepared via reversible addition–fragmentation chain transfer (RAFT) radical polymerization using a PNaSS-based macro-chain transfer agent. The molecular weight distributions (Mw/Mn) of PNaSS–b–PAA and PNaSS–b–PNIPAM were 1.18 and 1.39, respectively, suggesting that these polymers have controlled structures. When aqueous solutions of PNaSS–b–PAA and PNaSS–b–PNIPAM were mixed under acidic conditions, water-soluble PNaSS–b–PAA/PNaSS–b–PNIPAM complexes were formed as a result of hydrogen bonding interactions between the pendant carboxylic acids in the PAA block and the pendant amide groups in the PNIPAM block. The complex was characterized by 1H NMR, dynamic light scattering, static light scattering, and transmission electron microscope measurements. The light scattering intensity of the complex depended on the mixing ratio of PNaSS–b–PAA and PNaSS–b–PNIPAM. When the molar ratio of the N-isopropylacrylamide (NIPAM) and acrylic acid (AA) units was near unity, the light scattering intensity reached a maximum, indicating stoichiometric complex formation. The complex dissociated at a pH higher than 4.0 because the hydrogen bonding interactions disappeared due to deprotonation of the pendant carboxylic acids in the PAA block.

Gibbs Free Energy and Activation Free Energy of Complexation of Some Divalent Cations with Ampicillin in Methanol at Different Temperatures

The Complexation reaction between Sodium (2S,5R,6R)-6-{[(2R)-2-amino-2-phenylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate (Ampicillin sodium salt) ligand with Ca+2 and Ba+2 ions were studied condctometrically in methanol at four different temperatures (293.15K, 298.15K, 303.15K, 308.15K) On drawing the relation between molar conductance and the ratio of metal to ligand concentrations, different lines are obtained indicating the formation of (1:1 and 2:1 (M:L) stoichiometric complexes. The formation constants, thermodynamic parameters Gibbs free energies and Gibbs free energies of formation of different complexes in methanol were determined.

Exploring the structure and stability of cholesterol dimer formation in multicomponent lipid bilayers.

For 40 years, the existence and possible functional importance of cholesterol dimer formation has been discussed. Due to challenges associated with structural studies of membrane lipids, there has as yet been no direct experimental verification of the existence and relevance of the cholesterol dimer. Building on recent advances in lipid force fields for molecular simulation, in this work the structure and stability of the cholesterol dimer is characterized in POPC bilayers in absence and presence of sphingomyelin. The cholesterol dimer structural ensemble is found to consist of sub-states that reflect, but also differ from, previously proposed dimer structures. While face-to-face dimer structures predominate, no evidence is found for the existence of tail-to-tail dimers in POPC lipid bilayers. Near stoichiometric complex formation of cholesterol with sphingomyelin is found to effect cholesterol dimer structure without impacting population. Comparison with NMR-derived order parameters provide validation for the simulation model employed and conclusions drawn related to the structure and stability of cholesterol dimers in multicomponent lipid bilayers. © 2016 Wiley Periodicals, Inc.

PH-sensitive Wormlike Micelle and Hydrogel Formation by Acylglutamic Acid–Alkylamine Complex

pH-sensitive viscoelastic fluids were obtained through the formation of wormlike micelles and hydrogels. These assemblies result from the 1:1 stoichiometric complex formation of acylglutamic acid (...

Stoichiometry of the eIF2B complex is maintained by mutual stabilization of subunits.

The eukaryotic translation initiation factor eIF2B is a multi-subunit complex with a crucial role in the regulation of global protein synthesis in the cell. The complex comprises five subunits, termed α through ε in order of increasing size, arranged as a heterodecamer with two copies of each subunit. Regulation of the co-stoichiometric expression of the eIF2B subunits is crucial for the proper function and regulation of the eIF2B complex in cells. We have investigated the control of stoichiometric eIF2B complexes through mutual stabilization of eIF2B subunits. Our data show that the stable expression of the catalytic eIF2Bε subunit in human cells requires co-expression of eIF2Bγ. Similarly, stable expression of eIF2Bδ requires both eIF2Bβ and eIF2Bγ+ε. The expression of these subunits decreases despite there being no change in either the levels or the translation of their mRNAs. Instead, these subunits are targeted for degradation by the ubiquitin-proteasome system. The data allow us to propose a model for the formation of stoichiometric eIF2B complexes which can ensure their stoichiometric incorporation into the holocomplex.

Conformational energetics of insulin in interpolyelectrolyte complexes insulin-poly(methylaminophosphazene) under near-physiological conditions

Interaction of a synthetic biodegradable polymer, poly(methylaminophosphazene), (PMAP) with human recombinant zinc insulin at pH 7.4 and different ionic strengths was studied by means of turbidimetry, phase analysis and high-sensitivity differential scanning calorimetry. The formation of stoichiometric (insoluble) and non-stoichiometric (soluble) interpolyelectrolyte Insulin-PMAP complexes was detected. It was shown that binding of zinc insulin to PMAP is accompanied by conversion of the protein to its zinc-free form as a result of the Zn+2 release from the insulin native structure. The conformational stability of the bound zinc-free insulin is defined by composition of the complexes. It increases in case of the non-stoichiometric complexes and decreases in the stoichiometric ones. We found that soluble Insulin-PMAP complexes revealed thermoresponsive properties within physiological range of temperature and ionic strength.

Complexation of bovine serum albumin with cationic polyelectrolytes at pH 7.40 – Formation of soluble complexes

Complexation of bovine serum albumin (BSA) with the cationic polymer poly([3-(methacryloylamino)propyl]trimethylammonium chloride) (PMAPTAC) and its graft copolymer with poly(N, N-dimethylacrylamide), (PMAPTAC-g-PDMAM75), was investigated at pH=7.40, in water, and in 0.15M NaCl, close to physiological conditions, as a function of the Polycation/BSA charge ratio, r. Turbidity, and UV absorption measurements, indicated the formation of insoluble stoichiometric complexes between BSA and PMAPTAC in water, but not in 0.15M NaCl. A potentiometric study, in agreement with this behavior, showed proton release for the BSA/PMAPTAC mixtures in water, but not in 0.15M NaCl. In the case of the mixtures of BSA with the graft copolymer PMAPTAC-g-PDMAM75, the solutions obtained even in water, were clear. Nevertheless, soluble complex formation in water was confirmed by potentiometry, ζ-potential and static light scattering measurements, while in 0.15M NaCl not any complex formation was detected.

A α-cyanostilbene-modified Schiff base as efficient turn-on fluorescent chemosensor for Zn 2 +

A novel Schiff base derivative (Z)-3-(4-(hexyloxy)phenyl)-2-(4-((E)-2-hydroxybenzylidene amino)phenyl)acrylonitrile (L) was designed, synthesized and characterized. L was used as a Zn2+ selective, turn-on, fluorescent chemosensor with a detection limit of 0.1 μM in DMF. 1:1 stoichiometric complex formation of L wih Zn2+ was confirmed through fluorescent titration experiments and Job’s plot. The enhancement of fluorescence intensity of L with addition of Zn2+ is the consequence of the inhibited isomerization of the C=N bond, namely chelation-enhanced fluorescence (CHEF) effect. α-Cyanostilbene-modified Schiff L was designed as a highly selective and sensitive zinc chemosensor. The complexation of L with Zn2+ enhanced the fluorescence intensity. This chemosensor could distinguish clearly Zn2+ from Cd2+, a frequently encountered trouble in the design for the Zn2+ fluorescent probes.

Synthesis and Characterization of Nano‐Encapsulated Black Pepper Oleoresin using Hydroxypropyl Beta‐Cyclodextrin for Antioxidant and Antimicrobial Applications

Previous studies have reported antimicrobial and antioxidant activity of black pepper oleoresin which is associated to its phenolic compounds and piperine. The ability of cyclodextrins to form an inclusion complex with a guest molecule could improve black pepper oleoresin application, bioavailability, and stability in foods. Hydroxypropyl beta-cyclodextrin (HPBCD) inclusion complex with black pepper olereosin were synthesized using the kneading method and characterized for its physico-chemical properties and its antioxidant and antimicrobial activities. Inclusion complex size was 103.9 ± 7.6 nm and indicated to be a polydisperse system. The entrapment efficiency was 78.3 ± 3.6%, which suggests that other constituents in black pepper oleoresin have higher affinities for HPBCD than piperine (major compound in black pepper oleoresin). Thermograms showed the disappearance of oxidation peaks of black pepper oleoresin, proving complex formation with HPBCD. Phase solubility results indicated 1:1 stoichiometric inclusion complex formation and an increase of black pepper oleoresin aqueous solubility with HPBCD concentration. Nano-encapsulation with HPBCD did not affect (P > 0.05) total phenolic content; however, it enhanced (P < 0.05) black pepper oleoresin antioxidant activity. Black pepper oleoresin and its inclusion complex were analyzed for their antimicrobial activity against Escherichia coli K12 and Salmonella enterica serovar Typhimurium LT2. Both free and encapsulated black pepper oleoresin effectively inhibited bacterial growth within the concentration range tested. Black pepper oleoresin encapsulated in HPBCD was able to inhibit Salmonella at lower (P < 0.05) concentrations than its corresponding free extract. Therefore, black pepper oleoresin-HPBCD nanocapsules could have important applications in the food industry as antimicrobial and antioxidant system.

Selective fluorescence sensing of ferric ion with novel triazolethione Schiff bases probes

Abstract New triazolethione Schiff base derivatives 3a–f were synthesized. The structures of the products were characterized by elemental analysis, 1H NMR, 13C NMR, IR and MS. Their complexation properties to different heavy and transition metal ions were studied by UV-Vis and fluorescence spectroscopy. Compound 3a shows selective recognition of Fe3+ with a 1:1 stoichiometric complex formation.

Water-soluble complexes formed from hydrogen bonding interactions between a poly(ethylene glycol)-containing triblock copolymer and poly(methacrylic acid)

Poly(sodium styrenesulfonate)-block-poly(ethylene glycol)-block-poly(sodium styrenesulfonate) (PSS–PEG–PSS) was prepared via reversible addition-fragmentation chain transfer (RAFT) radical polymerization of sodium styrenesulfonate (SS) using a poly(ethylene glycol) (PEG)-based bifunctional macro-chain transfer agent in water. The reaction proceeded in the manner of living polymerization, suggesting that the number-average molecular weight increased linearly with monomer conversion, whereas the molecular weight distribution remained nearly constant below 1.30, independent of conversion. Poly(methacrylic acid) (PMA) homopolymer was also prepared via RAFT. When aqueous solutions of PSS–PEG–PSS and PMA were mixed below pH 5, water-soluble PSS–PEG–PSS/PMA complexes were formed as a result of hydrogen bonding interactions between the PEG block and the pendant carboxylic acids in PMA. The complex was characterized by 1H NMR spin–spin relaxation time, light scattering and transmission electron microscopy measurement techniques. The hydrodynamic radius (Rh) of the complex depended on the mixing ratio of the PSS–PEG–PSS and PMA molecules. When the mole ratio of ethylene glycol units in PSS–PEG–PSS and the pendant carboxylic acids in PMA was nearly unity, the scattering intensity and Rh exhibited maximum values for PSS–PEG–PSS and PMA, which is indicative of stoichiometric complex formation. The complex dissociated at pH greater than 5 because the hydrogen bonding interaction ceased as a result of deprotonation of the pendant carboxylic acids in PMA. Poly(sodium styrenesulfonate)-block-poly(ethylene glycol)-block-poly(sodium styrenesulfonate) (PSS–PEG–PSS) and poly(methacrylic acid) (PMA) homopolymer were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. When aqueous solutions of PSS–PEG–PSS and PMA were mixed below pH 5, water-soluble PSS–PEG–PSS/PMA complexes were formed due to hydrogen bonding interactions between the PEG block and the pendant carboxylic acids in PMA.

Trivalent Actinide and Lanthanide Complexation of 5,6-Dialkyl-2,6-bis(1,2,4-triazin-3-yl)pyridine (RBTP; R = H, Me, Et) Derivatives: A Combined Experimental and First-Principles Study

Complexations of lanthanide ions with 5,6-dialkyl-2,6-bis(1,2,4-triazin-3-yl)pyridine [RBTP; R = H (HBTP), methyl (MeBTP), ethyl (EtBTP)] derivatives have been studied in the acetonitrile medium by electrospray ionization mass spectrometry, time-resolved laser-induced fluorescence spectroscopy, and UV-vis spectrophotometric titration. These studies were carried out in the absence and presence of a nitrate ion in order to understand the effect of the nitrate ion on their complexation behavior, particularly in the poor solvating acetonitrile medium where strong nitrate complexation of hard lanthanide ions is expected. Consistent results from all three techniques undoubtedly show the formation of lower stoichiometric complexes in the presence of excess nitrate ion. This kind of nitrate ion effect on the speciation of Ln(3+) complexes of RBTP ligands has not so far been reported in the literature. Different Am(3+) and Ln(3+) complexes were observed with RBTP ligands in the presence of 0.01 M tetramethylammonium nitrate, and their stability constant values are determined using UV-vis spectrophotometric titrations. The formation of higher stoichiometric complexes and higher stability constants for Am(3+) compared to Ln(3+) ions indicates the selectivity of these classes of ligands. A single-crystal X-ray diffraction (XRD) study of europium(III) complexes shows the formation of a dimeric complex with HBTP and a monomeric complex with EtBTP, whereas MeBTP forms both the dimeric and monomeric complexes. Density functional theory calculations confirm the findings from single-crystal XRD and also predict the structures of Eu(3+) and Am(3+) complexes observed experimentally.

Pd-Catalyzed Synthesis of Dibenzofurans by Phenol-Directed C-H Activation

Reported is the synthesis of dibenzofurans 2 from 2-arylphenols 1 via palladium-catalyzed phenol-directed C-H activation/C-O cyclization. Control experiments (formation of stoichiometric Pd complexes and isotope labeling studies) showed that C-O reductive elimination was the rate-limiting step. Accordingly, the bulky additive MesCO2Na was found to increase the yield by promoting reductive elimination. A broad range of functionalities (including acid-sensitive groups, heterocycles, and even sugars) are tolerated, many of which provide synthetic handles for further functionalization. To demonstrate the orthogonality of this method with an established ­related carbazole synthesis (J. A. Jordan-Hore, C. C. C. Johansson, M. Gulias, E. M. Beck, M. J. Gaunt J. Am. Chem. Soc. 2008, 130, 16184), compound 3 was prepared by selective C-O coupling to form the dibenzofuran followed by C-N coupling to afford the carbazole.