Liquid Ordered Phase of Binary Mixtures Containing Dipalmitoylphosphatidylcholine and Sterols

The effect of cholesterol, desmosterol, stigmasterol, sitosterol, ergosterol, and androsterol on the phase behavior of aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) was studied to understand the role of the side chain in the formation of ordered phases of the type observed in membrane rafts. Thermotropic changes in the structure of mixed dispersions and transition enthalpies were examined by synchrotron X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The observations indicated that cholesterol was more efficient than phytosterols (stigmasterol and sitosterol) or ergosterol in its interaction with DPPC to form the liquid ordered phase (L_o). The L_o induced by cholesterol or desmosterol was stable over a wide temperature range, whereas, the liquid ordered phase containing phytosterols or ergosterol was profoundly dependent on temperature, which should be distinguished as L_oβ and L_oα, representing the phases below and above the main transition temperature. The characteristics in forming ordered structures of cholesterol and other sterols imply that the evolution may have selected cholesterol as the most efficient sterol for animals to form rafts in their cell membranes.     

Ganglioside‐Selective Mechanosensitive Fluorescent Membrane Probes

The development of fluorescent probes to image forces in cells is an important challenge in chemistry and biology. Planarizable push‐pull probes have been introduced recently for this purpose. To provide most valuable information on forces in complex systems, these mechanosensitive ‘flipper’ probes will have to be localized by molecular recognition of targets of interest. Here we report fluorescent flippers that selectively recognize gangliosides on the surface of lipid bilayer membranes by formation of dynamic covalent boronate esters. The original flipper probes were equipped with 2‐fluorophenyl boronic acids and benzoboroxoles using consecutive triazole and oxime ligation. Evaluation was done in large unilamellar vesicles composed of EYPC/SM/CL/GM 40:40‐x:20:x to obtain mixed membranes with separate liquid‐disordered (L_d) and ganglioside (GM) containing liquid‐ordered (L_o) domains. With increasing GM concentration, fluorescence intensities increased and excitation maximum shifted to the red. Deconvolution of the spectra confirmed that these changes originate from a migration of the flipper probes from L_d to L_o domains upon binding to the gangliosides and thus the planarization in the more ordered environment. Control mechanophores without boronic acids failed to show the same response, and fructose partially inhibited the ganglioside sensitivity. These results demonstrate that it is possible to selectively accumulate mechanosensitive flipper probes in L_o domains and, more generally, that probe localization in complex membranes is possible and matters.     

Creating and Modulating Microdomains in Pore‐Spanning Membranes

The architecture of the plasma membrane is not only determined by the lipid and protein composition, but is also influenced by its attachment to the underlying cytoskeleton. Herein, we show that microscopic phase separation of “raft‐like” lipid mixtures in pore‐spanning bilayers is strongly determined by the underlying highly ordered porous substrate. In detail, lipid membranes composed of DOPC/sphingomyelin/cholesterol/Gb₃ were prepared on ordered pore arrays in silicon with pore diameters of 0.8, 1.2 and 2 μm, respectively, by spreading and fusion of giant unilamellar vesicles. The upper part of the silicon substrate was first coated with gold and then functionalized with a thiol‐bearing cholesterol derivative rendering the surface hydrophobic, which is prerequisite for membrane formation. Confocal laser scanning fluorescence microscopy was used to investigate the phase behavior of the obtained pore‐spanning membranes. Coexisting liquid‐ordered‐ (l_o) and liquid‐disordered (l_d) domains were visualized for DOPC/sphingomyelin/cholesterol/Gb₃ (40:35:20:5) membranes. The size of the l_o‐phase domains was strongly affected by the underlying pore size of the silicon substrate and could be controlled by temperature, and the cholesterol content in the membrane, which was modulated by the addition of methyl‐β‐cyclodextrin. Binding of Shiga toxin B‐pentamers to the Gb₃‐doped membranes increased the l_o‐phase considerably and even induced l_o‐phase domains in non‐phase separated bilayers composed of DOPC/sphingomyelin/cholesterol/Gb₃ (65:10:20:5).     

Rhodium catalyzed hydroacylation of ethylene with 4-pentenals. reactions of 4-hexenal-1-d

A catalyst derived from 2,4-pentanedionatobis(ethylene)rhodium(I), I, promoted the addition of 4-pentenal to ethylene. The reaction was accompanied by the formation of double bond migration products derived from the 4-pentenal reactant and from the 6-hepten-3-one primary product. Compound I accomplished the addition of 4-hexenal to ethylene to afford high yields of 6-octen-3-one. The fate of the aldehyde hydrogen in this transformation has been determined in experiments employing 4-hexenal-1-d as reactant. Treatment of 4-hexenal-1-d with I in CHCl₃ and CDCl₃ afforded 6-octen-3-one possessing >50% d_o molecules while the isotopic composition of recovered unexpended 4-hexenal remained >96% d₁. 6-Octen-3-one products with isotopic compositions of >66% d_o were afforded when ethylene was introduced to reaction mixtures. The location of deuterium in 6-octen-3-one, derived from treatment of 4-hexenal-1-d with I in the absence of added C₂H₄, was determined to be distributed at C-1 and C-2 and at the CC bond by analysis of the ¹H and ²H NMR spectra. Unexpended ethylene was recovered and was found to contain a substantial amount of deuterium. Mechanistic implications of these results are discussed.     

Electromediators based on the Ni(II) and Cr(III) complexes with the redox-active ligands in the synthesis of sulfur-containing organic compounds

The chromium(III) tris-o-semiquinolate complex Cr(L^SQ)₃ (L^SQ is 3,6-di-tert-butyl-o-semiquinone) and the monoanionic paramagnetic nickel(II) complex [n-Bu₄N][Ni(L _S ^SQ )(L _S ^DT )] (L _S ^SQ is o-thiosemiquinone, L _S ^DT is benzene-1,2-dithiolate) are considered as electromediators of hydrogen sulfide oxidation in the presence of various organic substrates (hex-1-ene, oct-1-ene, benzene, toluene, and benzoic acid). It is revealed that the electrolysis of hydrogen sulfide at the oxidation potential of the mediators in the presence of the substrates affords the corresponding aliphatic and aromatic thiols in a yield of 62–75%.     

High‐Fidelity Protein Targeting into Membrane Lipid Microdomains in Living Cells

Lipid analogues carrying three nitrilotriacetic acid (tris‐NTA) head groups were developed for the selective targeting of His‐tagged proteins into liquid ordered (l_o) or liquid disordered (l_d) lipid phases. Strong partitioning into the l_o phase of His‐tagged proteins bound to tris‐NTA conjugated to saturated alkyl chains (tris‐NTA DODA) was achieved, while tris‐NTA conjugated to an unsaturated alkyl chain (tris‐NTA SOA) predominantly resided in the l_d phase. Interestingly, His‐tag‐mediated lipid crosslinking turned out to be required for efficient targeting into the l_o phase by tris‐NTA DODA. Robust partitioning into l_o phases was confirmed by using viral lipid mixtures and giant plasma membrane vesicles. Moreover, efficient protein targeting into l_o and l_d domains within the plasma membrane of living cells was demonstrated by single‐molecule tracking, thus establishing a highly generic approach for exploring lipid microdomains in situ.     

Quadruple thermo-photo-redox-responsive random copolypeptide nanogel and hydrogel

Quadruple stimuli-responsive random copolypeptide of poly(methoxydiethyleneglycol-L-glutamate)-co-poly(S-(o-nitrobenzyl)-L-cysteine) was synthesized by ring-opening copolymerization, simultaneously presenting thermo-photo-redox-responsive self-assembly behavior and forming nanogel and hydrogel in water.     

Influence of the composition of aqueous dimethylsulfoxide solvent on thermodynamics of complexing between 18-crown-6-ether and D,L-alanine

Standard thermodynamic parameters (logK ^o, ??_r H ^o, T??_r S ^o) of complexing 18-crown-6 ether (18C6) with D,L-alanine (Ala) in mixed water-dimethysulfoxide (H₂O-DMSO) solvents are calculated on the basis of calorimetric titration results. A rise in the DMSO concentration in mixed solvent is found to increase stability and increase the exothermicity of the formation of [Ala-18C6] molecular complex. Changes in the reaction energetic are shown to be determined by changes in the solvation state of 18C6 that is the characteristic of the reactions of molecular complex formation between 18C6 and D,L-alanine or glycine in water-organic solvents.     

ESR investigation of the substitution reactions in rhodium(I) complexes with spin-labeled ligands

A number of new spin-labelled Rh^I complexes containing both the 3,6-ditert-butyl-o-benzosemiquinone (3,6-SQ) fragment and n- and π-donor ligands have been prepared. The tetracoordinate derivatives of the composition L₂Rh-(3,6-SQ), where L  CO, P(OPh)₃, L  1/2 1,5-COD and the pentacoordinate complex (PPh₃)₂Rh(3,6-SQ)(CO) were isolated in individual state, the formation of other rhodium compounds was registered by ESR spectroscopy. The presence of an o-benzosemiquinolate ligand in the molecule with the unpaired electron located essentially on this fragment does not significantly influence on the reactivity of the metal ion in most cases; the n- and π-donor ligands exchange reactions studied by ESR confirm this fact. (PPh₃)₂Rh(3,6-SQ) has an abnormal distribution of spin density of the unpaired electron in the molecule, mostly located on the metal atom, this derivative bearing a close analogy to the rhodium(II) (d⁷) complexes.     

Enthalpy characteristics of dissolution of L-tryptophan in water + formamides binary solvents at 298.15 K

Enthalpies of dissolution of L-tryptophan in aqueous solutions of formamide (FA), N-methylformamide (MFA), and N,N-dimethylformamide (DMF) are measured according to calorimetry at the concentration of amides x ₂ = 0?0.4 mole fraction. Standard values of enthalpies of dissolution and transfer Δ_tr H ^o of L-tryptophan from water to binary solvent, as well as enthalpy coefficients of pair-wise interactions h _xy of L-tryptophan with formamide molecules are calculated. The effect the composition of a waterorganic mixture has on the enthalpy characteristics of L-tryptophan is considered. The relation of Δ_tr H ^o of L-tryptophan with the structure of amides is shown. A quantitative estimation of the contributions to the energy of L-tryptophan-formamide pair-wise interactions determined by polarity/polarizability, acidity, and basicity of organic solvent is performed using the four-parameter Kamlet-Taft correlation equation.     

The structure, photo-induced magnetization and correlation of the cyano-bridged two-dimensional hetero-bimetallic compounds

Two new 3d-4f cyano-bridged hetero-bimetallic compounds with distinguished two-dimensional honeycomb network structure, {Ln(HP)₂(H₂O)₃(μ-NC)₃Fe(CN)₃}_n, (Ln=Ce, Nd; HP=4-Hydroxypyridine) were synthesized and crystallographically characterized. A novel photo-induced magnetization phenomenon for {Nd(HP)₂(H₂O)₃(μ-NC)₃Fe(CN)₃}_n, was revealed and studied. Furthermore, the correlation between photo-induced magnetization and structure was proposed.     

Heat transfer from a transferred-arc plasma to a cylindrical enclosure

Hear-transfer rates from an axially enclosed transferred arc to a surrounding water-cooled cylindrical sleeve, 15 cm high, were measured. The arc (argon or nitrogen) was struck between a movable cathode within the sleeve and a bath of molten copper below the sleeve, serving as anode. The distance from the bottom of the sleeve to the surface of the molten copper (L _o) was constant. Variables studied were the diameterD of the sleeve (5, 7.5. and 10 cm), the length of the arc within the sleeveL (5, 10, and 15 cm), the currentI (200, 250, and 300 A) and a tangential flow of gas or vortex within the sleeve (0, ?0, and 50 liters/min). The total power transferred to the sleeve,P _s was measured caloronetrically and was the sure ofP _r the effective power radiated by the arc of lengthL within the sleeve.P _a, the power radiated into the sleeve from the arc of length L_o below the sleeve, andP _o , the power radiated from the melt surface (a constant of small value), minusP _a , the power lost by convection from the sleeve (negligible, except for a strong vortex). BothP _r andP _o were found to be equal to the product of the Joule heat released within their respective arc lengths, IV_gL and IV_g0L₀ (where V_g and V_g0 are the voltage gradients), and dimenonless efliciency factors, η_r and η₀. which are functions ofL/D andL ₀ /D, respectively, for each gas, regardless of the geometry of the sleeve, the current, and the strength of the vortex.     

The importance of concentration effects at the electrode surface in anodic stripping voltammetric measurements of complexation of metal ions at natural water concentrations

The influence of the ligand/metal ion concentration ratio on the shape, peak current and peak potential of curves obtained by anodic stripping voltammetry (a.s.v.) at the hanging mercury drop electrode is described, particularly with respect to the use of a.s.v. for speciation of metal ions at very low concentrations as is often found in natural waters. The lead(II)/triethylenetetramine system is used as a model of a fully labile reversible system. It is shown that the total metal ion concentration at the electrode surface (C^o_M) during the stripping step may be much larger (30–300 times in typical conditions) than that in the bulk solution (C_M), the exact value depending on the deposition time t_d. Consequently, changes in the peak characteristics are observed when the ligand/metal concentration ratio in the bulk of the solution, C_L/C_M, is less than 1000. Semi-empirical equations, experimentally tested, are given, which enable C^o_M/C_M to be estimated for a specified solution and a.s.v. conditions, which correct for the “surface concentration effect” when a.s.v. is used to measure complexation, and which describe the influence of the parameters such as stirring efficiency, radius of the mercury drop and C_L/C_M. The implications of the results are discussed for determinations of total metal ion in complex media, of speciation based on peak-potential shifts or stripping voltammetric curves, and of complexation capacity.     

Das verhalten von mono- und diorganylphosphansulfiden gegenüber metallcarbonylsystemen: VII . Präprative,kinetische und spektroskopische untersuchungen über die isomerisierung verschiedener sekundärer phosphansulfide an carbonylsystemen von metallen der VI. nebengruppe

Cycloheptatrienemolybdenum tricarbonyl reacted with ligands (L) (L = phenyl-, o-tolyl-, m-tolyl-, p-tolyl-, α-naphthyl-, β-naphthyl-, sym-diphenyl-, sym-di-o-tolyl-, sym-di-p-tolyl, or sym-di-α-naphthyl-thiourea) to give Mo(CO)₅L derivatives although the expected products were cis-Mo(CO)₃L₃. Evidence has been obtained for the formation of trans-Mo(CO)₄L₂ derivatives when L = sym-diphenyl- and sym-di-o-tolyl-thiourea. These donors on reaction with Mo(CO)₄B (B = o-phenanthroline or 2,2′-bipyridine) yielded mixed ligand derivatives of the type Mo(CO)₃BL. The appearance of three CO stretching bands is in agreement with the C_s symmetry of mixed-ligand molybdenum carbonyls.     

Synthesis of bioactive 2-(2-(difluoromethoxy)aryl)benzo[d]thiazole derivatives via base-promoted one-pot process

A convenient synthesis of 2-(2-(difluoromethoxy)aryl)benzo[d]thiazoles from 2- (o-hydroxyaryl)benzothiazoles and commercially available ethyl difluoroiodoacetate (ICF₂CO₂Et) is described. The transformation was amenable to a one-pot, sequential three-component protocol from o-hydroxybenzaldehyde, o-aminothiophenol, and ICF₂CO₂Et promoted by KOH. Additionally, some of the prepared compounds exhibited promising activity against human ovarian cancer cells.     

Bioreduction of methyl o-chlorobenzoylformate at 500 g L without external cofactors for efficient production of enantiopure clopidogrel intermediate

Biocatalytic reduction of methyl o-chlorobenzoylformate (CBFM) provides a green and direct access to methyl (R)-o-chloromandelate [(R)-CMM], an intermediate for a platelet aggregation inhibitor named clopidogrel. As much as 500 g L⁻¹ of CBFM was stoichiometrically converted into enantiopure (R)-CMM at 20 °C by using a whole-cell catalyst coexpressing an aldo-keto reductase from Bacillus sp. and a glucose dehydrogenase (GDH). In addition to the high productivity of 812 g L⁻¹ d⁻¹, this new whole-cell reduction is attractive by eliminating the need of an added external cofactor.     

Steric effects on the electronic and molecular structures of nickel(II) and cobalt(II) 2,6-dipyrazol-1-ylpyridine complexes

The complexes [M(L¹R)₂](BF₄)₂ (M=Ni, Co; L¹R=2,6-dipyrazol-1-ylpyridine [L¹H], 2,6-bis-{3-iso-propylpyrazol-1-yl}pyridine [L¹Prⁱ], 2,6-bis-{3-phenylpyrazol-1-yl}pyridine [L¹Ph], 2,6-bis-{3-[2,4,6-trimethylphenyl]pyrazol-1-yl}pyridine [L¹Mes]) and [M(L²)₂](BF₄)₂ (M=Ni, Co; L²=2-{3-[2,4,6-trimethylphenyl]pyrazol-1-yl}-6-{5-[2,4,6-trimethylphenyl]pyrazol-1-yl}pyridine) have been prepared. Single crystal structure determinations of [M(L¹H)₂](BF₄)₂ (M=Ni, Co) and solvates of [Ni(L¹Mes)₂](BF₄)₂, [Co(L¹Mes)₂](ClO₄)₂ and [Co(L²)₂](BF₄)₂ all show six-coordinate metal centres with local near-D_2d symmetry. The L¹Mes and L² mesityl substituents have only a small effect on the MN{pyrazole} (M=Ni, Co) bond lengths in these compounds. The d–d spectra of the complexes show that L¹Mes is a significantly better donor ligand than L¹H, L¹Prⁱ or L¹Ph, and that L¹Prⁱ is a weaker ligand than might be expected purely on inductive grounds. A combination of UV–Vis/NIR, EPR, NMR and magnetic measurements have demonstrated that all the Co(II) compounds are high-spin in the solid state and in solution at 290 K.     

Electrochemical transformations and anti/prooxidant activity of sterically hindered <Emphasis Type="Italic">o</Emphasis>-benzoquinones

The electrochemical properties of a series of sterically hindered o-benzoquinones in aprotic solvents were examined. The reaction of O₂ and KO₂ with o-benzoquinones and electrogenerated o-semiquinone radical anions was studied. The formation of o-semiquinone radical anions in the reactions of KO₂ with the studied o-quinones was detected using UV-visible and ESR spectroscopy. The influence of the test compounds on lipid peroxidation was considered at the molecular and tissue levels in vitro. In the most cases, o-quinones exhibit antioxidant activity, which varies depending on the type of lipid substrate.     

Photocalorimetric measurement of the heat flow during optically and thermally induced solid state reaction between Ag and As33S67 thin films

Thin films of amorphous chalcogenide with composition of As₃₃S₆₇ (thickness d = 300 nm) and silver film (thickness d = 30 nm) on top of chalcogenide film were deposited by vacuum thermal evaporation. Prepared bilayer Ag/As₃₃S₆₇ was illuminated and photo-induced dissolution and diffusion (OIDD) process of silver in chalcogenide film studied by means of photocalorimetry. The heat flow connected with OIDD process during light exposure as a function of light energy, light intensity and temperature has been studied by means of photocalorimetry. The enthalpies of OIDD process were obtained and attributed to the bond energies of the formed bonds.     

Copper complexes of two isomeric NS2-macrocycles

Two isomeric NS₂-macrocycles incorporating a xylyl group at ortho (o -L) and meta (m -L) positions were employed and their copper complexes (1?C5) were prepared and structurally characterized. The copper(II) nitrate complexes [Cu(L)(NO₃)₂] (1: L = o -L, 2: L = m -L) for both ligands were isolated. In each case, the copper center is five-coordinated with a distorted square pyramidal geometry. Despite the overall geometrical similarity, 1 and 2 show the different ligand conformation due to the discriminated packing pattern. Reaction of o -L with copper(II) perchlorate afforded complex 3 containing two independent complex cations [Cu(o -L)(H₂O)(DMF)(ClO₄)]⁺ and [Cu(o -L)(H₂O)(DMF)]²⁺; the coordination geometry of the former is a distorted octahedron while the latter shows a distorted square pyramidal arrangement. In the reactions of copper(I) halides (I or Br), o -L gave a mononuclear complex [Cu(o-L)I] (4) with a distorted tetrahedral geometry, while m -L afforded a unique exodentate 2:1 (ligand-to-metal) complex [trans-Br₂Cu(m-L)₂] (5) adopting a trans-type square-planar arrangement.