Variations in the condensing effect of cholesterol on saturated versus unsaturated phosphatidylcholines at low and high sterol concentration

In this work, we have investigated the condensing and ordering effect induced by cholesterol on phosphatidylcholines (PCs). To perform the studies systematically, for the experiments we have selected phospholipids differing only in the number of cis monounsaturated chains (1,2-distearoyl-sn-glycero-3-phosphocholine--DSPC, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine--SOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine--DOPC) or in the length (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine--POPC vs SOPC) of sn-1 acyl chain. Because the cholesterol concentration in mammalian membranes can be as high as 70 mol % of total lipids, the investigations were performed in a wide range of the sterol content. The results of the Langmuir monolayer experiments evidence that the relation between the structure of hydrophobic part of PC and the magnitude of the effects induced by cholesterol found at lower sterol content is different from that observed at higher sterol concentration. At a lower concentration of sterol (up to 30%), the condensing effect of cholesterol is stronger on saturated DSPC than on PCs containing monounsaturated chain(s), which is consistent with the conclusions drawn by other authors. However, at higher sterol content (≥50%), saturated DSPC is less susceptible to the influence of sterol than the investigated unsaturated PCs. To explain these irregularities, we have considered the strength of van der Waals interactions as well as the influence of sterol on the tilt of polar heads of PCs. It was also found that in the whole range of sterol concentration the ordering effect is stronger on saturated DSPC as compared to unsaturated phospholipids. However, at lower sterol content (up to 30%) the ordering effect induced on unsaturated PCs is rather weak, and the ordering does not change drastically in comparison with pure PCs film.     

Syntheses, reactivity and DFT studies of group 2 and group 12 metal complexes of tris(pyrazolyl)methanides featuring "free" pyramidal carbanions

Reactions of HC(Me2pz)3 with Grignard reagents, dialkyl magnesium compounds and dimethylzinc are reported, together with a DFT study on some of the aspects of this chemistry. Reactions of HC(Me2pz)3 with MeMgX (X=Cl or Br) gave the half-sandwich zwitterionic compounds [Mg((Me)Tpmd)X] (X=Cl (2) or Br (3); (Me)Tpmd(-)=[C(Me2pz)3](-)). Addition of HCl to 2 gave the structurally characterised half-sandwich compound [Mg{HC(Me2pz)3}Cl2(thf)] (4). The zwitterionic sandwich compound [Mg(MeTpmd)2] (5) formed in low yields in the reaction of MeMgX with HC(Me2pz)3 but was readily prepared from HC(Me2pz)3 and either MgnBu2 or MgPh2. The structurally characterised compound 5 contains two "naked" sp3-hybridised carbanions fully separated from the dicationic metal centre. Only by using MgPh2 as starting material could the half-sandwich compound [Mg(MeTpmd)Ph(thf)] (6) be isolated. The zwitterionic sandwich compound 5 reacted with HOTf (OTf(-)=[O3SCF3](-)) to form the dication [Mg{HC(Me2pz)3}2]2+ (7(2+)), which was structurally characterised. Pulsed field gradient spin-echo (PGSE) diffusion NMR spectroscopy revealed both compounds to be intact in solution. In contrast to the magnesium counterparts, HC(Me2pz)3 reacted only slowly with ZnMe2 (and not at all with ZnPh2) to form the half-sandwich zwitterion [Zn(MeTpmd)Me] (8), which contains a cationic methylzinc moiety separated from a single sp3-hybridised carbanion. Density functional calculations on the zwitterions [M(MeTpmd)Me] and [M(MeTpmd)2] (M=Mg, Zn) revealed that the HOMO in each case is a (Me)Tpmd-based carbanion lone pair. The kappa 1C isomers of [M(MeTpmd)Me] were calculated to be considerably less stable than their kappa 3N-bound counterparts, with the largest gain in energy for Mg due to the greater ease of electron transfer from metal to the (Me)Tpmd apical carbon atom on formation of the zwitterion. Moreover, the computed M-C bond dissociation enthalpies of the kappa 1C isomers of [M(MeTpmd)Me] are considerably higher than expected by simple extrapolation from the corresponding computed H-C bond dissociation enthalpy.     

Electronic spectra of 1-methyl and 2-methyl phenanthrenes and their radical cations

Electronic spectra of phenanthrene (P), 1-methyl phenanthrene (1-MeP), 2-methyl phenanthrene (2-MeP) and their monopositive ions are investigated experimentally as well as theoretically. The ions were produced by photo-oxidation of the hydrocarbons in boric acid matrix. The electronic absorption spectrum of 2-methyl phenanthrene cation (2-MeP+) is entirely new. For the interpretation of the electronic spectra of neutral and ionized MePs, semi-empirical AM1 (Austin Model 1) calculations are carried out for the first time. The bathochromic shifts in the spectral bands of the neutral and ionized MePs are attributed to 'conjugative' effect. The present experiments reveal that the 448 nm band of 1-methyl phenanthrene cation (1-MeP+) and the 486 nm band of 2-MeP+ show close matching with the respective 450 nm and 488 nm 'diffuse interstellar bands'. This suggests the possibility of the existence of such ionic species in the interstellar matter.     

Structure of a new sterol from the South China sponge Dysidea fragilis

A new sterol, 5a-cholesta-8(14),24(25)-diene-3/β, 6a-diol (1) and a known sterol (24Z)-24-ethyl-cholesta-7(8),24(28)-diene-3β,5a,6β-triol (2) have been isolated from the South China Seasponge Dysidea fragilis. The structure and relative stereochemistry of 1 were established by spectralanalysis, including 2D NMR experiments.     

Acid-base equilibriums of lumichrome and its 1-methyl, 3-methyl, and 1,3-dimethyl derivatives

Lumichrome photophysical properties at different pH were characterized by UV-vis spectroscopy and steady-state and time-resolved fluorescence techniques, in four forms of protonation/deprotonation: neutral form, two monoanions, and dianion. The excited-state lifetimes of these forms of lumichrome were measured and discussed. The results were compared to those obtained for similar forms of alloxazine and/or isoalloxazine, and also to those of 1-methyl- and 3-methyllumichrome and 1,3-dimethyllumichrome. The absorption, emission, and synchronous spectra of lumichrome, 1-methyl- and 3-methyllumichrome, and 1,3-dimethyllumichrome at different pH were measured and used in discussion of fluorescence of neutral and deprotonated forms of lumichrome. The analysis of steady-state and time-resolved spectra and the DFT calculations both predict that the N(1) monoanion and the N(1,3) dianion of lumichrome have predominantly isoalloxazinic structures. Additionally, we confirmed that neutral lumichrome exists in its alloxazinic form only, in both the ground and the excited state. We also confirmed the existence and the alloxazinic structure of a second N(3) monoanion. The estimated values of pK(a) = 8.2 are for the equilibrium between neutral lumichrome and alloxazinic and isoalloxazinic monoanions, with proton dissociation from N(1)-H and N(3)-H groups proceeding at the almost the same pH, while the second value pK(a) = 11.4 refers to the formation of the isoalloxazinic dianion in the ground state.     

Synthesis of the 3-methyl and 4-methyl derivatives of 3-amino-3,4-dihydro-1-hydroxycarbostyril and related compounds

The 3-methyl and 4-methyl derivatives of 3-amino-3,4-dihydro-1-hydroxycarbostyril were synthesized by the reductive cyclization of α-methyl-β-(o-nitrophenyl)alanine and α-amino-β-(o-nitrophenyl)butyric acid hydrohalides, respectively, under conditions of catalytic hydrogenation in acidic solution. The free bases of the latter two o-nitroaromatic amino acids were also catalytically hydrogenated under neutral conditions to yield the respective α-methyl-β-(o-aminophenyl)alanine and α-amino-β-(o-aminophenyl)butyric acid which were converted to the corresponding lactams, 3-methyl- and 4-methyl-3-amino-3,4-dihydrocarbostyrils. α-Methyl-β-(o-nitrophenyl)alanine was obtained by acid hydrolysis of 5-methy)-5-(o-nitrobenzyl)hydantoin which was prepared by treatment of o-nitrophenylacetone with potassium cyanide and ammonium carbonate. α-Amino-β-(o-nitrophenyl)butyric acid was synthesized by condensation of α-bromo-o-nitroethylbenzene with diethyl acetamidomalonate, followed by acid hydrolysis of the condensation product. The 4-methylated compounds were obtained as synthetic mixtures of two diasteromeric racemates in nearly the same amounts as shown by nmr spectral analysis. Unlike the demethylated parent compound, 3-amino-3,4-dihydro-1-hydroxycarbostyril, neither the 3-methyl nor 4-methyl analog was found to possess any antibacterial activity.     

Structural determination of two lipids isolated from the sea urchin <Emphasis Type="Italic">Echinometra lucunter</Emphasis>

Specimens of the sea urchin Echinometra lucunter were collected at Dakar (Senegal). Fresh sea urchins were exhaustively treated with CHCl₃–MeOH 1:1 (v/v). After evaporation of solvent the oily residue (1, 92 g) was passed through an RP 18 column. The CHCl₃ soluble fraction has been analyzed through spectroscopic means (NMR, electrospray ionization mass spectrometry). It has been shown to contain the two sterol derivatives lucunterperacetate (1) and peroxylucunterine (2).     

Rotational dynamics of the methyl group in the 4-methyl pyridine crystal

Raman spectra below 150 cm⁻¹ of the 4-methyl pyridine crystal, and its deuterated derivative (d₇), at various temperatures from 276.8 K (melting point) to 5 K are presented and vibrational assignments proposed. Three crystal phases are observed between 5–100 K (III), 100–254 K (II) and 254–276.8 K (I). In phase III, where the site symmetry for the molecule is C₁, different potential shapes are compared and only a non-periodic function accounts satisfactorily for the five τCH₃ and two τCD₃ Raman bands. A molecular model is proposed where the methyl groups are correlated along infinite chains in the crystal.     

Raney nickel reductions—VIII A synthesis of 1:2-benzanthracene and its 3′-methyl and 4-methyl derivatives

1:2-Benzanthracene and the 3′-methyl derivative have been prepared by Raney nickel reduction of the sulphuric esters of the leuco derivatives of 1:2-benzanthraquinone and 4′-chloro-3′-methyl-1:2-benzanthraquinone, followed by dehydrogenation. 3-Hydroxy-1:2-benzanthraquinone was methylated in the 4-position by formaldehyde, sodium hydrosulphite and sodium hydroxide solution (the Marschalk reaction). Simultaneous reduction of the nuclear hydroxyl and quinone groups was effected by Raney nickel reduction of the trisulphuric ester of 3:9:10-trihydroxy-4-methyl-1:2-benzanthracene, and the resultant hexahydro-4-methyl-1:2-benzanthracene was dehydrogenated to 4-methyl-1:2-benzanthracene. The preparation of 3:4:9:10-dibenzopyrene from Mayvat brilliant red AF by Raney nickel reduction of the sulphuric ester of the leuco derivative and subsequent dehydrogenation is described.     

First synthesis of free cholesterol-BODIPY conjugates

Analogues of cholesterol (compounds 1 and 2) and coprostanol (compound 3) containing the BODIPY fluorophore in the aliphatic tail of the free sterol have been synthesized starting with bisnorcholenic acid, cholenic acid 3beta-acetate, and lithocholic acid, respectively. An ester linkage joining the fluorophore to the sterol nucleus interfered with the ability of the fluorescent sterol to pack with phospholipids in monolayers. However, an analogue in which the linker was devoid of polar atoms exhibited a substantially similar physical behavior to cholesterol in model membranes with respect to localization in raft domains.     

Infrared and Raman spectra of vicinally trisubstituted 2-methyl, 3-chloroaniline and 2-methyl, 6-chloroaniline

The IR and Raman spectra of 2-methyl, 3-chloroaniline (2-M, 3-CA) and 2-methyl, 6-chloroaniline (2-M, 6-CA) have been recorded at room temperature in the region 3600-100 cm⁻¹. A vibrational analysis has been made using additional frequencies obtained from IR studies at 223 and 123 K and also including the polarization measurement of the Raman lines. A comparative study of these two molecules together with the spectra of 2,3-dimethylaniline (2,3-DMA), investigated earlier, has been presented. The anomalous behaviour of certain normal modes at low temperatures indicates the presence of an intermolecular hydrogen bonding of the N-H…N type in 2-M, 3-CA and 2,3-DMA, whereas, in 2-M, 6-CA, an intramolecular hydrogen bonding of the type N-H…Cl has been detected owing to the presence of the highly electronegative Cl atom at the ortho position.     

Effect of the "supersilyl" group on the reactivities of allylsilanes and silyl enol ethers

Kinetics of the reactions of allylsilanes (1) and silyl enol ethers (2) with benzhydrylium ions (3) were studied by UV-vis spectroscopy in dichloromethane at 20 °C. The less than three times higher reaction rates of the tris(trimethylsilyl)silyl compounds in comparison to the corresponding trimethylsilyl compounds indicate that the previously reported strong electron-donating effect of the supersilyl group operates only in the α-position and not in the β-position.     

Total syntheses of (-)-methyl atis-16-en-19-oate, (-)-methyl kaur-16-en-19-oate, and (-)-methyl trachyloban-19-oate by a combination of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement

Asymmetric total syntheses of (-)-methyl atis-16-en-19-oate (1c), (-)-methyl kaur-16-en-19-oate (2c), and (-)-methyl trachyloban-19-oate (3c) have been achieved by employing a hybrid strategy of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement. The common synthetic intermediate 5 was prepared from 2-allylcyclohexanone (4) with 98% ee using d'Angelo's asymmetric Michael addition. A series of functional group modifications in 5 via palladium-catalyzed cycloalkenylation led to (+)-14, which had already been prepared by us as racemate. (-)-Methyl atis-16-ene-19-oate (1c) was generated via homoallyl-homoallyl radical rearrangement. On the other hand, Wolff-Kishner reduction of 18 followed by esterification yielded (-)-methyl kaur-16-en-19-oate (2c) together with (-)-methyl trachyloban-19-oate (3c).     

Analysis of influence of the 5-methyl group on internal rotation of the vinyl group in 1-vinylpyrazoles,by the AM-1 method

According to results obtained in quantum-chemical calculations by the AM-1 method, 1-vinyl- and 1-vinyl-5-methylpyrazole may exist in the s-cis(N₂) and s-trans(N₂) conformations. The introduction of the CH₃ group into position 5 of the pyrazole ring gives a substantial increase in population of the s-cis form, and also increases the interval of torsional vibrations of the vinyl group around the equilibrium position.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2077–2079, September, 1991.     

联苯-2,2'-二甲酸-2-甲酯的合成、结构及表征

最新的药理活性试验表明, 具有联苯结构单元的化合物对于肝癌的标记物甲胎蛋白(AFP) 及人免疫病毒(HIV)有一定的作用[1,2]. 在金属催化和新型磁性材料合成方面, 化学家对以联苯二甲酸类物质桥联的配合物已进行了广泛研究[3～6].     

ESR study of gamma irradiated 2-methyl nylon3

Gamma radiation-induced radicals of 2-methyl nylon3 (2mN3) have been investigated by electron spin resonance spectrometry. The type of radicals generated, conversion into other radicalic species and their room temperature stability were evaluated. Two types of radicals have been detected. Two different formation mechanisms have been proposed for each radical. As suggested in literature for commercial polyamides, in our system we also observed two different radicals (R1 and R2). Among these radicals, R1 is expected to convert to R2, which is a chemically favorable process.     

Surfactants with an amide group "spacer": Synthesis of 3-(acylaminopropyl)trimethylammonium chlorides and their aggregation in aqueous solutions

The cationic surfactants RCONH(CH2)3N+(CH3)3Cl-, where RCO = C10, C12, C14, and C16, respectively, have been synthesized by reacting the appropriate carboxylic acids with 3-N,N-dimethylamino-1-propylamine, followed by dehydration of the ammonium salt produced. Reaction of the intermediates obtained (RCONH(CH2)3N(CH3)2) with methyl iodide, followed by chloride/iodide ion-exchange furnished the surfactants. Their adsorption and aggregation in aqueous solutions have been studied by surface tension, conductivity, EMF, static light scattering and FTIR. Additional information on the micellar structure was secured from effects of the medium on the 1H NMR chemical shifts and 2D ROESY spectra. Increasing the length of the acyl moiety increased the micelle aggregation number, and decreased the minimum area/surfactant molecule at the solution/air interface, the critical micelle concentration, and the degree of dissociation of the counter-ion. Gibbs free energies of adsorption at the solution/air interface and of micelle formation were calculated, and compared to those of 2-(acylaminoethyl)trimethylammonium chloride; alkyl trimethylammonium chloride; and benzyl(3-acylaminopropyl)dimethylammonium chloride surfactants. For both processes (adsorption and micellization), contributions of the CH2 groups in the hydrophobic tail and of the head-group to DeltaG0 were calculated. The former contribution was found to be similar to those of other cationic surfactants, whereas the latter one is more negative than those of 2-(acylaminoethyl)trimethylammonium chlorides and trimethylammonium chlorides. This is attributed to a combination of increased hydrophobicity of the head-group, and (direct- or water-mediated) intermolecular hydrogen-bonding of aggregated monomers, via the amide group. FTIR and NMR results indicated that the amide group lies at the micellar interface.     

Sterol composition of a cultured marine dinoflagellate,Heterocapsa circularisquama

The composition of sterols was determined in a cultured marine dinoflagellate Heterocapsa circularisquama. Ten kinds of the sterol in H. circularisquama were identified by capillary gas chromatography-mass spectrometry. The major sterol was a 4-methyl sterol, 4alpha,23,24-trimethyl-5alpha-cholest-22E-en-3beta-ol (dinosterol) which is the common sterol in many dinoflagellates.     

5α-24-Norcholestan-3β-ol and (24Z)-Stigmasta-5,7,24(28)-trien-3β-ol,Two New Marine Sterols from the Pacific Sponges Terpios zeteki and Dysidea herbacea

The steroidal components of 2 marine sponges, Terpios zeteki (from Hawaii) and Dysidea herbacea (from Australia) were fractionated through a combination of chromatographic methods, including reversed phase HPLC., and were analyzed by a combination of physical methods, including high resolution GC.-MS. and 360 MHz ¹H-NMR. T. zeteki contains 6 conventional 5α-stanols which comprise 91% of the sterol mixture, and traces (0.5%) of a new C₂₆ sterol, 5α-24-norcholestan-3β-ol. Minor amounts of conventional Δ⁵-sterols (6.5%) and of a single Δ⁴-3-ketosteroid (1.5%) were also present. In contrast, the Australian sponge (D. herbacea) contains 3 Δ^5,7-sterols which comprise 1.5% of the sterol mixture, and one new C₂₉ sterol, (24 Z)-stigmasta-5,7,24(28)-trien-3β-ol, as the major component (75%). In addition, minor amounts of conventional 5α-stanols (0.5%), Δ⁵-sterols (5%) and 5α-Δ⁷-sterols (18%) were present in this complex sterol mixture. The possible dietary or endosymbiotic origins of these sterols are discussed.     

Main constituents from the seeds of Vietnamese Cnidium monnieri and cytotoxic activity

From the ethyl acetate extract of the seeds of Vietnamese Cnidium monnieri L., three coumarins, osthole (1), xanthotoxin (2), imperatorin (3) and a sterol, daucosterol (4) have been purified. Their structures were elucidated by spectroscopic analysis. Furthermore, 8-(3-hidroxy-3-methylbutyl)-7-methoxycoumarin (5) was synthesised from osthole (1) with a good yield (80%). In addition, compound 1 and its synthesis product (5) show moderate and non-selective cytotoxic activities against four cancer cells, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma).