A Fucosylated Lactose-Presenting Tetravalent Glycocluster Acting as a Mutual Ligand of Pseudomonas aeruginosa Lectins A (PA-IL) and B (PA-IIL)—Synthesis and Interaction Studies

The Gram-negative bacterium Pseudomonas aeruginosa is an important opportunistic human pathogen associated with cystic fibrosis. P. aeruginosa produces two soluble lectins, the d-galactose-specific lectin PA-IL (LecA) and the l-fucose-specific lectin PA-IIL (LecB), among other virulence factors. These lectins play an important role in the adhesion to host cells and biofilm formation. Moreover, PA-IL is cytotoxic to respiratory cells in the primary culture. Therefore, these lectins are promising therapeutic targets. Specifically, carbohydrate-based compounds could inhibit their activity. In the present work, a 3-O-fucosyl lactose-containing tetravalent glycocluster was synthesized and utilized as a mutual ligand of galactophilic and fucophilic lectins. Pentaerythritol equipped with azido ethylene glycol-linkers was chosen as a multivalent scaffold and the glycocluster was constructed by coupling the scaffold with propargyl 3-O-fucosyl lactoside using an azide-alkyne 1,3-dipolar cycloaddition reaction. The interactions between the glycocluster and PA-IL or PA-IIL were investigated by isothermal titration microcalorimetry and saturation transfer difference NMR spectroscopy. These results may assist in the development of efficient anti-adhesion therapy for the treatment of a P. aeruginosa infection.     

Synthesis, Analysis, and Field Activity of Sordidin, a Male-Produced Aggregation Pheromone of the Banana Weevil, Cosmopolites sordidus

An efficient synthesis of the diastereoisomers of sordidin (1), a male-produced aggregation pheromone of Cosmopolites sordidus, has been developed from commercially available 4-methylpent-4-en-2-ol (2). Preparation of exo-β-sordidin (1a) and endo-β-sordidin (1b) is via the anti epoxide, 4d, which is derived via iodocarbonation of 2. The endo-α-sordidin (1c) and exo-α-sordidin (1d) are prepared from the corresponding syn epoxide, which is available via stereo-controlled epoxidation of the triisopropylsilyloxy derivative, 3b. Silyloxy derivatives of the epoxides, 4, efficiently alkylate the anions of N-cyclohexyldiethylketimine (6a) and 3-pentanone N,N-dimethylhydrazone (6b). Acidic work-up of these alkylation reactions promotes cyclization to give 1. Gram quantities of 1a?1d, 1a + 1b and 1c + 1d have been prepared by this route. In field tests in a banana plantation in Costa Rica, compounds 1a?1d significantly increased capture rates of standard pseudostem traps. Comparable numbers of adults were attracted to pseudostem traps baited with the major naturally occurring isomers of sordidin 1c + 1d or 1a?1d. Although addition of the minor naturally occurring isomers of sordidin (1a and 1b) to pseudostem traps increased capture rates above controls, these compounds did not increase attraction of pseudostem traps to the same extent as 1a?1d. In comparison tests with conventional pseudostem traps, significantly more adults were trapped in water-containing pitfall traps baited with 1a?1d.     

Positions and Stereochemistry of Methyl Branches in the Novel Sex Pheromone Components Produced by a Lichen Moth, Lyclene dharma dharma

Female moths of Lyclene dharma dharma (Arctiidae, Lithosiinae) produce three sex pheromone components (I–III), for which we assigned the following novel chemical structures; 6-methyl-2-octadecanone (1) for I, 14-methyl-2-octadecanone (2) for II, and 6,14-dimethyl-2-octadecanone (3) for III. In the Iriomote Islands where the insects were collected, a lure including racemic 1 and 2 attracted the male moths without mixing 3. In this study for further confirmation of the plane structures, the positional isomers with a methyl branch at the 4-, 5-, 7-, 13-, or 15-position (4–8, respectively) were synthesized. The GC-MS analyses revealed that natural components I and II were best fitted with those of 1 and 2, respectively, among the methyl-2-octadecanones examined, indicating the usefulness of this analytical instrument and authentic standards for the determination of the positions of methyl branches. In field trapping tests, 4–8 could not substitute for 1 or 2, nor did these compounds inhibit the active binary lure of 1 and 2, indicating that the males strictly recognized the 2-ketones with a methyl branch at the 6- or 14-positions. Next, the absolute configurations of I and II were determined by HPLC with a normal-phased chiral column (Chiralpak AD-H), which could separate the enantiomers of both 1 and 2. The chiral HPLC analysis of a crude pheromone extract indicated that the females exclusively produced (S)-1 and (S)-2. Furthermore, a field evaluation of each enantiomer revealed that (S)-1 and (S)-2 were bioactive but (R)-1 and (R)-2 were not.     

A Series of Luminescent Lanthanide–Organic Complexes Constructed from In Situ Generated Dithiobenzoic Acid

Two types of lanthanide thiolato-carboxylate complexes, [Type I: [Yb(dtba) (Hdtba)] _n (1), Type II: [Ln(dtba)_1.5(biim)] _n (Ln = Pr (2a), Nd (2b), Sm (2c), Eu (2d), Gd (2e), Tb (2f), Dy (2g), H₂dtba = 2,2′-dithiodibenzoic acid, bimm = diimidazole)] have been obtained by hydrothermal method and characterized by the single-crystal X-ray diffraction, IR, 2D-COS IR, TG and the luminescence analysis. The H₂dtba ligand came from the in situ S–S function reaction of 2-mercaptobenzoic acid (H₂mba) under the hydrothermal condition. Complex 1 is a 2D bamboo-like sqr-topology layered structure, and the 3D (4, 4, 6)-connected supramolecular frameworks is produced by the hydrogen bonds of O–H···O. Complexes of type II (from 2a to 2g) are isostructural and they are assigned to 1D rope-like chains by introducing the chelating ligand of diimidazole. These 1D rope-like chains are further linked by N–H···O hydrogen bonds into a 3D supramolecular framework with CdSO₄-type topology. Photoluminescence studies reveal that complexes 2b, 2c, 2d, 2f, 2g exhibit strong lanthanide characteristic emission bands in the solid state at room temperature.     

Synthesis,characterization and evaluation of antioxidant and anticancer activities of novel benzisoxazole-substituted-allyl derivatives

A novel series of various 2-allylbenzo[d]isoxazol-3(2H)-ones were synthesized using benzo[d]isoxazol-3(2H)-one treated with different allyl bromides/chlorides in the presence of water-mediated cesium carbonate as a new catalyst 3(a-h). The structures of the newly synthesized Benzisoxazole-substituted-allyl derivatives were characterized by spectroscopic methods and mass spectrometry. These synthesized compounds were evaluated for their in vitro antioxidant and anticancer activity. Compounds 3b, d, f, h were identified as the best hit against HT-29 Human colon cancer cells. Similarly, compounds like 3b, d, f, h showed significant antioxidant activity compared to the standard drug butylated hydroxy toluene (BHT).      

Construction of Three New Coordination Polymers Based on Dicarboxylate and Different Organic N-Donor Ligands

Three new metal coordination polymers, {[Ni₂(L₁)₂(bip)₂]·H₂O} _n (1), [Zn₂(L₂)₂(bih)_0.5] _n (2) and [Cd(L₂)(bih)_0.5] _n (3) [H₂L₁?=?2-(3-carboxyphenoxy)benzoic acid, H₂L₂?=?2-(4-carboxyphenoxy) benzoic acid, bip?=?4,4??-bis(2-imidazol-1-ylmethyl) biphenyl and bih?=?1,6-bis(2-methylimidazol-1-yl) hexane], have been synthesized and structurally characterized by elemental analysis, IR and X-ray diffraction. Compound 1 is a one-dimensional ladder-like chain structure. Compound 2 is a two-dimensional layer structure. In compound 3, the alternate arrangement of the right- and left-handed helical chains through bih ligands interactions, which lead to form a two-dimensional framework. In compound 1, 2 and 3, the L₁ and L₂ ligands act as bridging ligands, exhibiting three coordination modes to link metal ions: bis-monodentate, bidentate chelating and monodentate modes. Moreover, the luminescent properties of compound 2 and 3 were also investigated in this work.     

Influence of two breakfast meals differing in glycemic load on satiety, hunger, and energy intake in preschool children

Background

Glycemic load (GL) is the product of glycemic index of a food and amount of available carbohydrate in that food divided by 100. GL represents quality and quantity of dietary carbohydrate. Little is known about the role of GL in hunger, satiety, and food intake in preschool children. The aim of this study was to investigate the effect of two breakfast meals differing in GL on hunger, satiety, and subsequent food intake at lunch in preschool children aged 4-6 y.

Methods

Twenty three subjects consumed low-GL (LGL) and high-GL (HGL) breakfast meals according to a randomized crossover design followed by an ad libitum lunch 4 h after consumption of breakfast. Children were asked to consume meals until they are full. Each treatment was repeated twice in non-consecutive days and data were averaged.

Results

Children in LGL group consumed significantly lower amounts of GL, total carbohydrate, energy, energy density, and dietary fiber and higher amounts of protein and fat at the breakfast compared to those in HGL group. Prior to lunch, children were hungrier in the HGL intervention group compared to the LGL intervention group (P < 0.03). However, no significant difference was observed between LGL and HGL intervention groups in the amount of food and energy consumed during lunch.

Conclusions

Decreased hunger in children prior to lunch in LGL group is likely due to higher protein and fat content of LGL breakfast. Diets that are low in GL can be recommended as part of healthy diet for preschool children.     

Seaweed intake and blood pressure levels in healthy pre-school Japanese children

Background

Low diet quality and depression symptoms are independently associated with poor glycemic control in subjects with type 2 diabetes (T2D); however, the relationship between them is unclear. The aim of this study was to determine the association between diet quality and symptoms of depression among Cuban-Americans with and without T2D living in South Florida.

Methods

Subjects (n = 356) were recruited from randomly selected mailing list. Diet quality was determined using the Healthy Eating Index-2005 (HEI-05) score. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Both linear and logistic regression analyses were run to determine whether or not these two variables were related. Symptoms of depression was the dependent variable and independent variables included HEI-05, gender, age, marital status, BMI, education level, A1C, employment status, depression medication, duration of diabetes, and diabetes status. Analysis of covariance was used to test for interactions among variables.

Results

An interaction between diabetes status, gender and HEI-05 was found (P = 0.011). Among males with a HEI-05 score ≤ 55.6, those with T2D had a higher mean BDI score than those without T2D (11.6 vs. 6.6 respectively, P = 0.028). Among males and females with a HEI-05 score ≤ 55.6, females without T2D had a higher mean BDI score compared to males without T2D (11.0 vs. 6.6 respectively, P = 0.012)

Conclusions

Differences in symptoms of depression according to diabetes status and gender are found in Cuban-Americans with low diet quality.     

Synthesis of 6-Substituted 1-oxoindanoyl Isoleucine Conjugates and Modeling Studies with the COI1-JAZ Co-Receptor Complex of Lima Bean

The conjugates of 6-substituted 1-oxoindanoyl carboxylic acids with L-isoleucine are mimics of the plant hormone (+)-7-iso-JA-L-Ile (3) that controls and regulates secondary metabolism and stress responses. In order to generate ligands that can be used as hormone-like compounds possessing different biological activities, an efficient and short synthesis of 6-bromo-1-oxoindane-4-carboxylic acid opens a general route to 6-Br-1-oxoindanoyl L-isoleucine conjugate (Br-In-L-Ile) (9a) as a key intermediate for several bioactive 6-halogen-In-L-Ile analogs (7a, 8a, 10a). The 6-ethynyl-In-L-Ile analog (11a) might be a valuable tool to localize macromolecular receptor molecules by click-chemistry. The activities of In-Ile derivatives were evaluated by assays inducing the release of volatile organic compounds (VOCs) in lima bean (Phaseolus lunatus). Each compound showed slightly different VOC induction patterns. To correlate such differences with structural features, modeling studies of In-Ile derivatives with COI-JAZa/b/c co-receptors of P. lunatus were performed. The modeling profits from the rigid backbone of the 1-oxoindanonoyl conjugates, which allows only well defined interactions with the receptor complex.     

An Interesting Complex: [Cd(l -trp) (d-trp)] n

A novel coordination polymer [Cd(l-trp) (d-trp)] _n (where l-trp and d-trp are l-tryptophan and d-tryptophan or (S)-2-amino-3-(3-indolyl)propionic acid and (R)-2-amino-3-(3-indolyl)propionic acid) was prepared by a solvent-thermal method and characterized by elemental analysis, IR spectra and single-crystal X-ray diffraction. The compound(monoclinic space group P2(1)/c with a = 19.759(2) Å, b = 5.2496(10) Å, c = 9.7594(16) Å, β = 97.2760(10)°, Z = 2) shows a two-dimensional plane structure. The crystallized coordination polymer has a centrosymmetric space group. Each Cd²⁺ ion coordinates with a pair of racemes, and the complex is a mesomer. Although l-trp was used, both l-trp and d-trp appear in the complex.     

Effects of carbohydrates-BCAAs-caffeine ingestion on performance and neuromuscular function during a 2-h treadmill run: a randomized, double-blind, cross-over placebo-controlled study

Background

Carbohydrates (CHOs), branched-chain amino acids (BCAAs) and caffeine are known to improve running performance. However, no information is available on the effects of a combination of these ingredients on performance and neuromuscular function during running.

Methods

The present study was designed as a randomized double-blind cross-over placebo-controlled trial. Thirteen trained adult males completed two protocols, each including two conditions: placebo (PLA) and Sports Drink (SPD: CHOs 68.6 g.L^-1, BCAAs 4 g.L^-1, caffeine 75 mg.L^-1). Protocol 1 consisted of an all-out 2 h treadmill run. Total distance run and glycemia were measured. In protocol 2, subjects exercised for 2 h at 95% of their lowest average speeds recorded during protocol 1 (whatever the condition). Glycemia, blood lactate concentration and neuromuscular function were determined immediately before and after exercise. Oxygen consumption ( ), heart rate (HR) and rate of perceived exertion (RPE) were recorded during the exercise. Total fluids ingested were 2 L whatever the protocols and conditions.

Results

Compared to PLA, ingestion of SPD increased running performance (p = 0.01), maintained glycemia and attenuated central fatigue (p = 0.04), an index of peripheral fatigue (p = 0.04) and RPE (p = 0.006). Maximal voluntary contraction, , and HR did not differ between the two conditions.

Conclusions

This study showed that ingestion of a combination of CHOs, BCAAs and caffeine increased performance by about 2% during a 2-h treadmill run. The results of neuromuscular function were contrasted: no clear cut effects of SPD were observed.

Trial registration

ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00799630     

Simultaneous Growing of Two New Cd(II) Metal–Organic Frameworks with 2,6-Naphthalendicarboxylic Acid as New Precursors for Cadmium(II) Oxide Nanoparticles: Thermal, Topology and Structural Studies

Crystal structure and thermal stability of two new 3D Cd(II) metal–organic frameworks (MOF) containing 2,6-naphthalenedicarboxylate, [Cd(NDC)(DMF)], 1, and [Cd₃(NDC)₄], 2 (H₂NDC = 2,6-naphthalenedicarboxylic acid; DMF = N,N-dimethylformamide) have been studied. These two MOFs grow simultaneously within the same solution to give multiple crystals that are due to the general lability of Cd(II) complexes. Structure 1 shows a 3D neutral metal–organic framework with PtS topology and crystallizes in the triclinic system, space group P-1 (No. 2), whilst 2 crystallizes in the orthorhombic system, space group Fdd2 (No. 43) with body-centered cubic bcu-(4²⁴.6⁴) topology. The elongated nature of NDC results in large cavities in both compounds; however, the pores are filled by coordinated DMF molecules in 1. The thermal stability of 1 and 2 were studied by thermogravimetry and show stability to 400 °C for 1 and continuous weight loss for 2. CdO nanoparticles were prepared by direct calcination of 1 and 2 at 600 °C. The CdO nanoparticles were characterized by X-ray powder diffraction and its morphology were studied by scanning electron microscopy. The results show that the CdO is pure and has a uniform morphology.     

Sparing effects of selenium and ascorbic acid on vitamin C and E in guinea pig tissues

Background

Selenium (Se), vitamin C and vitamin E function as antioxidants within the body. In this study, we investigated the effects of reduced dietary Se and L-ascorbic acid (AA) on vitamin C and α-tocopherol (AT) status in guinea pig tissues.

Methods

Male Hartley guinea pigs were orally dosed with a marginal amount of AA and fed a diet deficient (Se-D/MC), marginal (Se-M/MC) or normal (Se-N/MC) in Se. An additional diet group (Se-N/NC) was fed normal Se and dosed with a normal amount of AA. Guinea pigs were killed after 5 or 12 weeks on the experimental diets at 24 and 48 hours post AA dosing.

Results

Liver Se-dependent glutathione peroxidase activity was decreased (P < 0.05) in guinea pigs fed Se or AA restricted diets. Plasma total glutathione concentrations were unaffected (P > 0.05) by reduction in dietary Se or AA. All tissues examined showed a decrease (P < 0.05) in AA content in Se-N/MC compared to Se-N/NC guinea pigs. Kidney, testis, muscle and spleen showed a decreasing trend (P < 0.05) in AA content with decreasing Se in the diet. Dehydroascorbic acid concentrations were decreased (P < 0.05) in several tissues with reduction in dietary Se (heart and spleen) or AA (liver, heart, kidney, muscle and spleen). At week 12, combined dietary restriction of Se and AA decreased AT concentrations in most tissues. In addition, restriction of Se (liver, heart and spleen) and AA (liver, kidney and spleen) separately also reduced AT in tissues.

Conclusion

Together, these data demonstrate sparing effects of Se and AA on vitamin C and AT in guinea pig tissues.     

Synthesis, Crystal Structures and Luminescence of Organic-Lanthanide Complexes with Nicotinic Acid and Adipic Acid Ligands

Two new lanthanide coordination polymers, [Sm₂(nic)₃(ad)_0.5(H₂O)(μ₃-O)₂] (1), [Pr(nic)(ad)]·2H₂O (2) (nic?=?nicotinic acid, ad?=?adipic acid) have been synthesized hydrothermally from the self-assembly of the lanthanide ions (Ln³⁺) with rigid nicotinic acid and the flexible adipic acid. They were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Structural analyses reveal that both of the complexes crystallize in triclinic, space group P-1 and have different framework characterization. Because of different coordination modes of nicotinate, complexes 1 and 2 exhibit 2D and 3D framework structure, respectively. In 1, the Sm1 and Sm2 atoms and their corresponding centrosymmetric atoms are connected by bridging oxygen atoms to form a 1D Sm₂(μ₃ -O)₂ polymeric chain along [010] direction. The photoluminescent properties of 1 and thermogravimetric analysis of 1 and 2 are discussed in detail.     

The Inclusion of Organometallic Derivatives of Cyclotriphosphazenes Inside SiO2 Matrix and Their Conversion to Nanostructured Metal-Oxides and Phosphates

Organometallic derivatives of the cyclotriphosphazene N₃P₃[OC₆H₄CH₂CN·TiClCp₂]₆ (1), N₃P₃(O₆H₅)₅[OC₆H₄N·W(CO)₅] (2), N₃P₃[OC₆H₄CH₂CN·Mo(CO)₅]₆ (3), [N₃P₃(O₆H₅)₅(OC₅H₄N·CpRu(PPh₃)₂)][PF₆] (4), [N₃P₃(O₂C₁₂H₈)₂OC₅H₄N·Ag(PPh₃)][OSO₂CF₃] (5), N₃P₃[OC₆H₅]₅ [OC₅H₄N·Cu][PF₆] (6) and N₃P₃[OC₆H₄CH₂CN·CuCl]₆[PF₆]₆ (7),were incorporated inside SiO₂ through the sol–gel method. The metal–organic nanocomposites of the general formula N₃P₃[OC₆H₄CH₂CN·TiClCp₂]₆·nSiO₂ (G ₁ ), N₃P₃[OC₆H₄N·W(CO)₅]·nSiO₂ (G ₂ ), N₃P₃[OC₆H₄CH₂CN·Mo(CO)₅]₆·nSiO₂ (G ₃ ), N₃P₃(O₆H₅)₅OC₅H₄N·CpRu(PPh₃)₂][PF₆]·nSiO₂ (G ₄ ), [N₃P₃(O₂C₁₂H₈)₂OC₅H₄N·Ag(PPh₃)][OSO₂CF₃]·nSiO₂ (G ₅ ), N₃P₃[OC₆H₅]₅[OC₅H₄N·Cu][PF₆]·(SiO₂) _n (G ₆ ), and N₃P₃[OC₆H₄CH₂CN·CuCl]₆[PF₆]₆·(SiO₂) _n (G ₇ ), were characterized by IR spectroscopy; ¹²C, ³¹ P and ²⁹Si MAS NMR measurements as well as UV–Visible diffuse reflectance spectra, indicating the presence of the respective organometallic derivatives of the cyclotriphosphazene incorporated into SiO₂. Pyrolysis of these nanocomposites under air at 800 °C gives rise to nanostructured metal-oxides and metal phosphates incorporated into amorphous SiO₂, with the presence in some cases of complexes phase mixtures. From some precursors, we obtained metal-oxides/phosphates nanoparticles separated from the SiO₂ nanoparticles instead the oxides/phosphates nanoparticles inside the SiO₂ matrix. Additionally and for comparison purposes, we used the compound N₃P₃[NH(CH₂)₃Si(OEt)₃]₆ as gelator. Nanocomposites (G′ ₁ ), (G′ ₂ ) and (G′ ₃ ) exhibited mainly morphological differences while in some cases composition differences when using TEOS as gelator. Some simple metal-containing compounds as (O₃SCF₃)Ag(PPh₃)(HOC₅H₄N), [CuCl₂·NC₅H₄OH] and [CuCl₂·NCCH₂C₆H₄OH]—which are useful models of the most complexes (G ₅ ), (G ₆ ) and (G ₇ ) were also prepared and incorporated in amorphous silica. Their pyrolytic products were compared with those of more complex cyclotriphosphazene analogous. Interestingly, the pyrolysis of the nanocomposite [(O₃SCF₃)Ag(PPh₃)(HOC₅H₄N)][SiO₂] _n affords the firstly-reported materials containing Ag₂O along with SiO₂ nanoparticles.     

Dietary intake and stress fractures among elite male combat recruits

Background

We examined the effect of four weeks of ??-alanine supplementation on isometric endurance of the knee extensors at 45% maximal voluntary isometric contraction (MVIC).

Methods

Thirteen males (age 23?±?6 y; height 1.80?±?0.05?m; body mass 81.0?±?10.5?kg), matched for pre-supplementation isometric endurance, were allocated to either a placebo (n?=?6) or ??-alanine (n?=?7; 6.4?g·d^-1 over 4?weeks) supplementation group. Participants completed an isometric knee extension test (IKET) to fatigue, at an intensity of 45% MVIC, before and after supplementation. In addition, two habituation tests were completed in the week prior to the pre-supplementation test and a further practice test was completed in the week prior to the post-supplementation test. MVIC force, IKET hold-time, and impulse generated were recorded.

Results

IKET hold-time increased by 9.7?±?9.4?s (13.2%) and impulse by 3.7?±?1.3 kN·s^-1 (13.9%) following ??-alanine supplementation. These changes were significantly greater than those in the placebo group (IKET: t ₍₁₁₎?=?2.9, p ??0.05; impulse: t ₍₁₁₎?=?3.1, p????0.05). There were no significant changes in MVIC force in either group.

Conclusion

Four weeks of ??-alanine supplementation at 6.4?g·d^-1 improved endurance capacity of the knee extensors at 45% MVIC, which most likely results from improved pH regulation within the muscle cell as a result of elevated muscle carnosine levels.     

Thermodynamics of Micellization of Sulfobetaine Surfactants in Aqueous Solution

The thermodynamics of micellization of the sulfobetaine (SB) amphoteric surfactants, that is N-alkyl-N,N-dimethyl-3-ammonio-1-propanesulfonate and N-alkyl-N,N-dimethyl-3-ammonio-1-butanesulfonate (the carbon atom number of the alkyl chain is 12, 14 and 16 respectively) in aqueous solution, have been studied by surface tension measurements with the temperature range from 298.15 to 318.15?K. The critical micelle concentrations (CMC) of SB n-3 and SB n-4 surfactants were determined from the drop-volume methods at different temperatures. The obtained results indicated that the values of critical micelle concentration strongly depended on the surfactants species and temperatures. Thermodynamic parameters ( $ \Updelta G_{\text{mic}}^{ \circ } $ , $ \Updelta H_{\text{mic}}^{ \circ } $ and $ \Updelta S_{\text{mic}}^{ \circ } $ ) of the micelle formation were determined. The micellization was found to be enthalpy-driven at lower temperatures, while this process was entropy-driven at higher temperatures. The enthalpy?Centropy compensation were also investigated. The compensation temperature T _c and $ \Updelta H_{\text{mic}}^{*} $ decreased, while $ \Updelta S_{\text{mic}}^{*} $ increased with the increase in the hydrophobic chain length.     

Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects

Background

With the increasing use of nanomaterials, the need for methods and assays to examine their immunosafety is becoming urgent, in particular for nanomaterials that are deliberately administered to human subjects (as in the case of nanomedicines). To obtain reliable results, standardised in vitro immunotoxicological tests should be used to determine the effects of engineered nanoparticles on human immune responses. However, before assays can be standardised, it is important that suitable methods are established and validated.

Results

In a collaborative work between European laboratories, existing immunological and toxicological in vitro assays were tested and compared for their suitability to test effects of nanoparticles on immune responses. The prototypical nanoparticles used were metal (oxide) particles, either custom-generated by wet synthesis or commercially available as powders. Several problems and challenges were encountered during assay validation, ranging from particle agglomeration in biological media and optical interference with assay systems, to chemical immunotoxicity of solvents and contamination with endotoxin.

Conclusion

The problems that were encountered in the immunological assay systems used in this study, such as chemical or endotoxin contamination and optical interference caused by the dense material, significantly affected the data obtained. These problems have to be solved to enable the development of reliable assays for the assessment of nano-immunosafety.     

Synthesis of 3,3-Dimethylbutanol and 3,3-Dimethylbutanal, Important Intermediates in the Synthesis of Neotame

It has been shown that some N-alkyl derivatives of Aspartame (1) are enhanced sweetening agents [1]. In particular, the 3,3-dimethylbutyl derivative, 2, (Neotame) is about 70?times sweeter than Aspartame. With this in mind a research program directed toward the synthesis of 3,3-dimethylbutanal (3) was begun. The first phase of this research involved the synthesis of 3,3-dimethylbutanol (4) by the acid catalyzed alkylation of isobutene with ethylene to give the sulfate ester [2] which was readily hydrolyzed to the alcohol, 4, in isolated yields in the 70?C75?% range. It was found that the most efficient method for the conversion of 4 to the aldehyde, 3, was by a vapor phase dehydrogenation over a copper catalyst. The effect which the reaction variables have on the production of 4 will be discussed. This will include factors such as the ethylene pressure, the acid/isobutene ratio, the use of a hydrocarbon solvent, the reaction temperature and the mode of addition of the isobutene. The discussion of the dehydrogenation procedure will include the nature of the catalyst used and the reaction parameters needed to maximize the formation of 3 and keeping the amount of the over-oxidation carboxylic acid product below 1?%.