Lipophilic Part Research Articles

Synthesis and Odor Properties of Substituted Indane‐2‐carboxaldehydes. Discovery of a New Floral (Muguet) Fragrance Alcohol

AbstractEight substituted indane‐2‐carboxaldehydes (= 2,3‐dihydro‐1H‐indene‐2‐carboxaldehydes), related to conformationally constrained analogues of floral‐type odorants, were synthesized in order to examine the effect of modifying the lipophilic part of the odorants (Schemes 1 and 2). None of the modified compounds showed better olfactive properties than the original ones (Tables 1 and 2), but an intermediate alcohol, 29, revealed itself as a valuable new member in the family of floral muguet (lily‐of‐the‐valley)‐type odorants.

Transitions induced by solubilized fat into reverse hexagonal mesophases

Lyotropic liquid crystals of glycerol monooleate (GMO) and water binary mixtures have been extensively studied and their resemblance to human membranes has intrigued many scientists. Biological systems as well as food mixtures are composed of lipids and fat components including triacylglycerols (TAGs, triglycerides) that can affect the nature of the assembly of the mesophase. The present study examines the effect of TAGs of different chain lengths (C 2–C 18) at various water/GMO compositions, on phase transitions from lamellar or cubic to reverse hexagonal (L α–H II and Q–H II). The ability of the triglycerides to promote the formation of an H II mesophase is chain length-dependent. It was found that TAG molecules with very short acyl chains (triacetin) can hydrate the head groups of the lipid and do not affect the critical packing parameter (CPP) of the amphiphile; therefore, they do not affect the self-assembly of the GMO in water, and the mesophase remains lamellar or cubic. However, TAGs with medium chain fatty acids will solvate the tails of the lipid, and will affect the CPP of the GMO, and transform the lamellar or cubic phases into hexagonal mesophase. TAGs with long chain fatty acids are very bulky, not very miscible with the GMO, and therefore, kinetically are very slow to solvate the lipid tails of the amphiphile and are difficult to accommodate into the lipophilic parts of the GMO. Their effect on the transitions from a lamellar or cubic phase to hexagonal is detected only after months of equilibration. In order to enhance the effect of the TAG on the phase transitions in the GMO/triglyceride/water systems, temperature and electrolytes effects were examined. In the presence of short and medium chain triglycerides, increasing temperature caused a transition from lamellar or hexagonal to L 2 phase (highest CPP value). However, in the presence of long chain TAGs, increasing temperature to ca. 40 °C caused a formation of H II mesophase. In addition, it was found that in tricaprylin/GMO/water systems, the increase in temperature caused a decrease in the lattice parameter. The effect of NaCl on the H II mesophase revealed interesting results. At low concentration of tricaprylin (5 wt%), the addition of only 0.1 wt% of NaCl was sufficient to cause the formation of well-defined H II mesophase, while further addition of electrolyte increased the hexagonal lattice parameters. At higher TAGs concentrations (10 wt%), addition of electrolyte resulted in the formation of H II with modifications of the lattice parameter. All the examined effects were more pronounced with increasing water content.

Effect of carbamate local anesthetics on NMDA receptors signaling: role of side chain position in lipophilic part

Effect of carbamate local anesthetics on NMDA receptors signaling: role of side chain position in lipophilic part

6-O-Sulfo sialylparagloboside and sialyl Lewis X neo-glycolipids containing lactamized neuraminic acid: Synthesis and antigenic reactivity against G159 monoclonal antibody

Synthesis and antigenic reactivity of 6-O-sulfo sialylparagloboside (SPG) and sialyl Lewis X (sLeX) neo-glycolipids containing lactamized neuraminic acid are described. The suitably protected GlcNAc-beta (1-->3)-Gal-beta (1-->4)-GlcOSE derivative was glycosylated with NeuTFAc-alpha (2-->3)-Gal imidate to give NeuTFAc-alpha (2-->3)-Galbeta (1-->4)-GlcNAc-beta (1-->3)-Gal-beta (1-->4)-GlcOSE pentasaccharide. The partial N,O-deacylation in the NeuTFAc-alpha (2-->3)-Gal part afforded N-deacetylated SPG derivative which was converted to the desired oligosaccharide containing lactamized neuraminic acid. Similar treatment of the sLeX hexasaccharide derivative, NeuTFAc-alpha (2-->3)-Gal-beta (1-->4) [Fuc-alpha (1-->3)]-GlcNAc-beta (1-->3)-Gal-beta (1-->4)-GlcOSE, gave the key hexasaccharide intermediate containing lactamized neuraminic acid. These suitably protected SPG and sLex oligosaccharides were converted stepwise into the desired neo-glycolipids (GSC-551 and GSC-552) by the coupling with 2-(tetradecyl)hexadecanol, 6-O-sulfation at C-6 of the GlcNAc residure, and complete deprotection. Both lactamized-sialyl 6-O-sulfo SPG (GSC-551) and sLex (GSC-552) neo-glycolipids were clearly recognized with G159 monoclonal antibody showing that both the lactamized neuraminic acid and the 6-O-sulfate at C-6 of GlcNAc would be involved in the G159-defined determinant. However, the Fuc residue and the lipophilic (ceramide) part may not be critical for this recognition.

Phase polymorphism by mixing of poly(oxyethylene)–poly(dimethylsiloxane) copolymer and nonionic surfactant in water

The phase behavior of the water/poly(oxyethylene)–poly(dimethylsiloxane) copolymer (Si 25C 3EO 51.6)/pentaoxyethylene dodecyl ether (C 12EO 5) ternary system has been studied. Both the silicone copolymer and the surfactant have equal volumes of hydrophilic and lipophilic parts; i.e., these are balanced amphiphiles. Although only a lamellar phase is observed in water–Si 25C 3EO 51.6 and water–C 12EO 5 binary systems, a variety of liquid crystalline phases, including normal micellar cubic (I 1), hexagonal (H 1), bicontinuous cubic (V 1), lamellar (L α ), reverse bicontinuous cubic (V 2), and reverse hexagonal (H 2), are observed in the copolymer-rich region of the ternary phase diagram. The small C 12EO 5 molecules dissolve at the hydrophobic interface in the thick bilayer of the Si 25C 3EO 51.6 L α phase occupying a large area of the total interface of the aggregates and modulate the curvature of the aggregates. Hence a variety of self-assembled structures are observed. In contrast, Si 25C 3EO 51.6 is not dissolved in the thin bilayer of the C 12EO 5 lamellar phase (L ′ α ). Hence, the C 12EO 5 L ′ α phase coexists with copolymer-rich L α and H 2 phases. Consequently, small surfactant molecules are dissolved in a large silicone copolymer aggregate to induce a change in layer curvature, but a large copolymer molecule is hard to incorporate with surfactant aggregates.

Surfactants in vaccine adjuvants: description and perspectives

Amphiphilic molecules, called surfactants, are made of a lipophilic part linked to a hydrophilic part. These substances have physicochemical properties of self-aggregation, solubilisation or emulsification. Their ability to be attracted at the same time by polar and non-polar compounds forces them to be at the interface. Surfactants most frequently used in vaccines can be of natural or synthetic origin, non-ionic, cationic or amphoteric with a formula weight between 600 and 4000 g/mol. They can be used as adjuvants, solubilisers or stabilisers of emulsions. Physicochemical properties are defined through solubility parameters or solution behaviours and hydrophilic lipophilic balance (HLB). Application properties are assessed through placebo formulations simulating the final use. Synthetic products are preferred to products of natural origin for quality reasons. Development of a new generation of surfactant with precise chemical definition and consistency may generate new candidates for potential vaccine adjuvants.

Cloud-Point Extraction for Selective Removal of Gd(III) and La(III) with 8-Hydroxyquinoline

:A less-common extraction procedure, cloud-point extraction, is used with a lipophilic chelating agent (8-hydroxyquinoline) to extract and separate lanthanum(III) and gadolinium(lll) ions from an aqueous solution. Surfactant solutions are used in conjunction with 8-hydroxyquinoline to form a lanthanide complex that is extracted into the micellar phase at a temperature above the cloud-point temperature. The structure of the lipophilic part of the nonionic surfactant, the chelating agent-metal molar ratio, and the cloud-point temperature are identified as factors determining the extraction efficiency and selectivity. With Triton X-114, a selectivity higher than 30 and a decontamination factor of 50 for Gd(IlI) indicate that micelle-mediated cloud-point extraction is promising for the specific separation of actinide ions from nuclear waste. Finally, a microwave procedure is proposed to decrease the duration of the experiment to less than 6 min.

In the Quest for a Virtual Pseudo Receptor for Sandalwood‐Like Odorants. Part I

Based on similarities between naturally occurring (-)-(Z)-beta- or (+)-(Z)-alpha-santalol ((-)- 1 or (+)-2, resp.) and the reversed (E)-configured synthetic derivatives from campholenal (7a), a simple model A was developed. Besides reconciliation of this stereochemical aspect, this initial model also tentatively explained the enantiodiscriminations as well as the large spectra of distances separating the OH function from the lipophilic quaternary center(s) reported for different classes of substrates. Evolution, modifications, and refinement of this imperfect model allied with the research for alternative possibilities are illustrated, along with a historical guideline, in the light of olfactively challenging synthetic seco-substructures as well as literature reports. Despite evolution of the inadequate model A and a plausible interpretation of the lipophilic part, the topological positions of the OH function and its vicinal alkyl substituent could nevertheless not be fully ascertained by this approach. This apparently inconclusive empirical concept prompted us to turn our attention towards a computerized methodology, which will constitute the second and third part of this study.

Phase System Selectivity and Peak Capacity in Liquid Column Chromatography ? the Impact on Two-Dimensional Separations

Correlations between the separation selectivity in aqueous and non-aqueous reversed-phase systems and in normal-phase systems were investigated. The degree of correlation between the selectivity in separation systems can be useful indicator of suitability of phase systems for two-dimensional HPLC separations. The real gain in peak capacity improves as the orthogonality of separation systems increases and impairs as the correlation between the selectivity of coupled systems increases. Similarity between the systems was determined on the basis of the change in retention (selectivity) attributed to suitable structural descriptors, such as polar interaction indices, number of carbon atoms in the lipophilic parts of the molecules or on number of repeat monomer units in high-molecular compounds. Based on this approach, the degree of orthogonality of the HPLC separation systems was evaluated and correlated with the peak capacity in two-dimensional HPLC. The approach was tested with simple aromatic compounds and was used to characterise retention behaviour of the individual species in samples of synthetic EO-PO co-polymers.

Interactions of complementary PEGylated liposomes and characterization of the resulting aggregates.

The interaction of complementary liposomes bearing both recognizable and protective ligands at their external surface has been investigated. Aggregation of hydrogenated phosphatidyl choline/cholesterol (2:1 molar ratio) based liposomes was mediated by the molecular recognition of the complementary phosphate and guanidinium groups incorporated in separate unilamellar liposomes. The phosphate group was incorporated in the bilayer employing dihexadecyl phosphate, while the guanidinium moiety was introduced in the membrane through the incorporation of various guanidinium lipids. For the latter, anchoring ability and primarily introduction of a spacer group between their lipophilic part and the guanidinium group was found to affect the ability for molecular recognition. Also, poly(ethylene glycol) (PEG) introduced in both types of liposomes at various concentrations and up to 15% with respect to cholesterol modifies the interaction effectiveness and morphology of the obtained aggregates. Interaction of these complementary liposomes leads to large precipitating aggregates or fused liposomes, as shown by phase contrast microscopy and dynamic light scattering. Specifically, fusion of liposomes takes place under a nonleaking process involving lipid mixing, as demonstrated by calcein entrapment and resonance energy transfer experiments. Calorimetric parameters also correlate with the processes of aggregation and fusion. The interactions of non-PEGylated liposomes involve exothermic processes of higher enthalpic content than those of the PEGylated counterparts.

Unsaturation Effect on Gelation Behavior of Aryl Glycolipids

Structurally simple, renewable-resource-based cardanyl (glucoside)s [1, 1-O-3'-n-(pentadecyl) phenyl-beta-D-glucopyranoside; 2, 1-O-3'-n-(8'(Z)-pentadeceenyl)-beta-glucopyranoside; 3, 1-O-3'-n-(8'(Z),11'(Z)pentadecadienyl)phenyl-beta-D-glucopyranoside, 4; 1-O-3'-n-(8'(Z),11'(Z),14'-pentadecatrienyl)phenyl-beta-D-glucopyranoside; and the mixture 5] form thermally reversible transparent gels in a water/alcohol mixture and a number of organic solvents, strongly influenced by the unsaturation of the aliphatic alkyl chain. DSC studies revealed that the Tgel of 1 in water/ethanol (1:1, vol/vol) gel is 69.0 degrees C, while of the introduction of a single double bond reduces the value to 30.0 degrees C in the case of monoene 2, indicating that the stability of the gel is related to the number of double bonds on the lipophilic part of the gelator. Furthermore, XRD measurements showed that the aqueous gel 1 maintains an interdigitated bilayered structure with 3.14 nm long-range ordering, and the corresponding organogel maintains an extended bilayer structure for 4.34 nm, indicating a clear difference in the aggregation behavior in different solvents.

Stationary-phase effects in gradient high-performance liquid chromatography

The type of the stationary phase for reversed-phase liquid chromatography significantly affects the sample polarity range that can be covered using gradients of organic solvents in water. The polarity range available for gradient separations of samples containing compounds differing in the lipophilic parts of the molecules can be characterized by “gradient lipophilic capacity”, Pl, based on the retention of standard compounds with a repeat lipophilic structural unit, such as a methylene group. The gradient lipophilic capacity is also suitable to characterize the separation possibilities of the columns in non-aqueous reversed-phase gradient elution of strongly non-polar compounds, such as triacylglycerols. In the same way, the suitability of various columns for reversed-phase gradient separations of oligomers can be characterized by “gradient oligomer capacity”, as demonstrated in the example of oligo(ethylene glycols). To enable a comparison of the properties of stationary phases independent of column efficiency and dimensions, the gradient lipophilic capacity or the gradient oligomer capacity should be normalized for a “standard” column plate number, gradient range and volume (in column hold-up volume units). The gradient lipophilic capacity or the gradient oligomer capacity and the number of compounds that can be resolved during a gradient run decrease as the initial concentration of the strong solvent in the mobile phase increases and (or) the gradient time decreases. These quantities can be used to select a suitable column and to adjust the optimum gradient profile (the initial composition of the mobile phase and the gradient steepness) with respect to the time of analysis and the number of oligomers or other compounds with regular repeat structural groups that can be resolved during the gradient run.

Synthetic studies towards the development of a novel class of acitretin-type retinoids

Trimethoxyaniline, indole-3-carboxylic acid and the dicarboxylic acids fumaric, maleic, succinic and phthalic have been combined to produce novel analogs of the aromatic retinoid acitretin. These analogs are characterized by a highly electron-rich benzene ring in the lipophilic part and two amide bonds, replacing the C7-C8 and C11-C12 double bonds, with simultaneous restriction of the C9-C10 double bond, in the spacer compared to acitretin. In addition, the terminal trans C13-C14 double bond has been either retained or isomerized or reduced or incorporated within an indole nucleus with simultaneous replacement of the carboxy group by the indole imine function. The related syntheses involved coupling of the N-Boc protected indole-3-carboxylic acid with 3,4,5-trimethoxyaniline, acid-mediated removal of the Boc group, coupling of the thus obtained anilide with the anhydrides or suitable monoesters of the above mentioned dicarboxylic acids in liquid or on solid phase and finally deprotection.

Die Behandlung der Psoriasis capillitii mit Dithranol

ZusammenfassungDithranol kann in den gebräuchlichen Fettgrundlagen am behaarten Kopf nicht angewendet werden und ist in abwaschbaren Zubereitungen zumindest in Deutschland wenig im Gebrauch. Mögliche Gründe dafür könnten sein, daß die Anwendung zu wenig bekannt ist, die Wirkung unterschätzt und Nebenwirkungen überschätzt werden. Wir haben deshalb die Fachliteratur zunächst nach Studien, dann nach Rezepturvorschlägen und Anwendungsempfehlungen und schließlich nach Berichten über Nebenwirkungen durchgesehen. Wir listen auf, welche dithranolhaltigen Fertigpräparate zur Kopfbehandlung in den europäischen Nachbarländern verfügbar sind, dazu die Empfehlungen für den Gebrauch und Warnhinweise für Nebenwirkungen.Weil das Dithranolmolekül sowohl hydrophile als auch lipophile Anteile aufweist, kann es auch leicht in Seifen inkorporiert werden. Die Stabilität solcher Zubereitungen ist zwar limitiert, in der Praxis ist die Wirksamkeit aber belegt, denn Dithranol in einem Detergens ist in der Hautklinik der Charité seit 20 Jahren in Gebrauch. Das spezielle, hier verwendete Vehikel, Biowaschöl, ist eine ölige flüssige Seife, die zur Reinigung stark verschmutzter Hände in der Industrie konzipiert wurde. Es ist am behaarten Kopf ebenso leicht aufzutragen wie ohne Seife auswaschbar. Wir berichten hier von der 1979 publizierten, ursprünglichen Studie von Meffert et al. mit Dithranol‐Biowaschöl, von den seither gemachten Erfahrungen und einer neuen, vergleichenden Studie, insbesondere über aufgetretene Nebenwirkungen, praktische Hinweise, Patientenkomfort und ‐urteil, die heute wichtige Kriterien darstellen.

Preliminary communication Liquid crystalline cardanyl β-D-glucopyranosides

Two novel aryl glycosides were synthesized, which varied in the extent of unsaturation in the lipophilic part, from plant/crop-based renewable resource materials. Their liquid crystalline properties were characterized by optical polarizing microscopy, differential scanning calorimetry and X-ray diffraction. All the mesophases are identified as lamellar in structure.

Spiro[pyrrolidine-2,2′-adamantanes]: synthesis, anti-influenza virus activity and conformational properties

Synthetic spiro[pyrrolidine-2,2′-adamantanes] 2, 3, 11, 15, 12, 16, 18, 20 were evaluated in vitro and found to be active anti-influenza virus A compounds; the effect of the position of C-Me pyrrolidine ring substituent on antiviral activity was examined. Pyrrolidine 5-Me substitution appears to be optimal for H 2N 2 strain activity. From the four different possible protonated conformers, experimental observation using NMR spectroscopy and molecular mechanics calculations demonstrated only a pair of conformers A +H ( N-Me ( ps-ax), C-Me ( ps-eq)) and B +H (( N-Me ps-ax, C-Me ps-ax)) which can contribute to the biological activity of C-Me, N-Me protonated derivatives 15 +H , 16 +H and 20 +H . The relative populations were calculated from NMR spectra. For compounds 15 +H and 20 +H conformer A +H ( cis dimethyl orientation) is the major one whereas a similar population of conformers A +H and B +H ( trans dimethyl orientation) was observed for compound 16 +H . Since this new series is characterized by a lipophilic part, that is the pyrrolidine ring, in addition to adamantane, that can interact with influenza A M2 protein, an ultimate future goal would be the in vitro mapping of M2 lipophilic pocket.

Phase Behavior of Poly(Oxyethylene)–Poly(Oxypropylene)–Poly(Oxyethylene) Block Copolymer in Water and Water–C12EO5 Systems

The binary phase diagram of a triblock copolymer poly(oxyethylene) (PEO) poly(oxypropylene) (PPO) poly(oxyethylene) (PEO), (PEO)37(PPO)58(PEO)37 or P105 in water and the ternary system of P105, water, and pentaoxyethylene dodecyl ether (C12EO5) has been studied to understand the miscibility of a small amphiphile, C12EO5 and a copolymer, as well as the mixing effect on the formed liquid crystalline structures. Phase diagrams, small angle x‐ray scattering (SAXS) and differential scanning calorimetry (DSC) were used to characterize these systems. The phase diagram of the binary system is presented together with the characteristic parameters for founded phases, namely, cubic, hexagonal, and lamellar phases. In the ternary system it was found that the small amphiphile and the block copolymer, despite having very different chain lengths are essentially miscible forming single phases. A large amount of C12EO5 can be solubilized in the P105 aggregates whereas P105 is most difficult to dissolve in the C12EO5 aggregates because of the difference in the molecular size. The copolymer is practically insoluble in the lamellar phase of C12EO5 due to the packing constraint. Hence, two lamellar phases coexist in a surfactant‐rich region, at W s = 0.66, where W s is the weight fraction of the total amphiphile in the system. This indicates that the thickness of the lipophilic part of the C12EO5 lamellar phase is too small to allocate the large lipophilic chain of the P105 triblock copolymer.

A Pseudo Thiacrown Compound Formed by Hydrophobic Interaction of Its Lipophilic Parts in Water: Ag+-Selective Fluorophore in Water

Amphiphilic podand (3) was prepared by conventional thioether synthesis in ethanol. It shows exclusive selectivity toward Ag + ion in a liquid-liquid extraction. It was also found to exhibit selective fluorescence decrease only in the presence of Ag + ion in water. From the fluorometric titration, the complexing stability constant toward Ag + in water estimated to be log Ka = 4.2, which value is comparable to cyclic dithia-18-crown-6. This extraordinarily high value was caused by a pseudo cyclic structure formed in water, which was supported by 1 H NMR spectral analysis.

Inhibition of serotonin re-uptake by licorice constituents.

Ovarian steroid hormones, estrogen and progestin, affect the function of the serotonin neural system by inhibiting serotonin re-uptake through allosteric interaction with the serotonin transporter (SERT) in a nongenomic mechanism. Blocking or reducing serotonin re-uptake at the synapse alleviates depression. The aim of this study was to test the effect of compounds of the isoflavan and isoflavene groups, subclasses of the flavonoids family, on serotonin re-uptake and to compare the results with the effect of other known phytoestrogens like genistein and daidzein to relate the activity of these compounds to their structure. The effect of these compounds on the re-uptake of radioactive serotonin was assayed in HEK-293 cells stably expressed the recombinant human serotonin transporter (hSERT). The results demonstrated that the isoflavans glabridin and 4'-O-methylglabridin (4'-OMeG) and the isoflavene glabrene inhibited serotonin re-uptake by 60, 53 and 47%, respectively, at 50 microM, whereas resorcinol, the isoflavan 2'-O-methylglabridin (2'-OMeG), and the isoflavones genistein and daidzein were inactive. The inhibition of serotonin re-uptake is dose dependant with glabridin and estradiol. These results emphasize the importance of the lipophilic part of the isoflavans, as well as the hydroxyl at position 2' on ring B. In conclusion, this study showed that several isoflavans are unique phytoestrogens, which like estradiol, affects the serotonergic system and inhibits serotonin re-uptake and, thus, potentially may be beneficial for mild to moderate depression in pre- and postmenopausal women.

Characterization and comparison of HPLC columns for gradient elution

The type of the stationary phase for reversed-phase liquid chromatography significantly affects the sample polarity range that can be covered using gradients of acetonitrile or of methanol in water. The polarity range available for gradient separations of samples containing compounds differing in the lipophilic parts of the molecules can be characterized by “lipophilic capacity”,Pl, based on the retention of retention standards with regular differences in lipophility, such as homologous alkylbenzenes. “Standard”Pl is defined as a quantity independent of the column dimensions and efficiency. It is controlled mainly by the chemistry of the bonded phase and by the properties of the support materials, but depends significantly also on the nature of the organic solvent in the mobile phase. The gradient lipophilic capacity and the sample polarity range that can be eluted during a “standardized” gradient run were used to compare the gradient-elution performance of more than 20 columns packed with various C8, C18 and other bonded phase materials on polymeric, monolithic, non-porous and superficially porous supports with various shielding of the residual silanol groups, including “aqueous phase” materials designed for the applications in highly aqueous mobile phases. The “lipophilic capacity” approach can be extended to characterize, the suitability of various columns for gradient separations of oligomers and lower polymers, as demonstrated on the example of lower poly(ethylene glycols).