cis-UROCANIC ACID FAILED TO AFFECT in vitro HUMAN LANGERHANS CELL ALLOSTIMULATORY FUNCTION

Abstract— -Urocanic acid (UCA) represents the major ultraviolet B (UVB, 290–320 nm)-absorbing component of the skin. Trans-UCA is naturally produced in the stratum corneum and converts to the cis isomer upon UVB irradiation. In this study, we examined the effect of purified cis -UCA (about 99% of cis isomer) on the human Langerhans cell (LC) allostimulatory function by using the mixed epidermal cell-lymphocyte reaction (MELR). We found that addition of increasing amounts (6.5–400 μg/mL) of purified cis-UCA or (rara-UCA did not modify the T-cell response supported by enriched LC (eLC: 8–25% LC) as well as purified LC (pLC: 70–90% LC) suspensions. Because cis-UCA had no effect on the allostimulatory function of untreated LC, we investigated whether this compound could modify T-cell proliferation induced by UVB-irradiated LC. The UVB exposure of eLC or pLC to 100 J/m² significantly inhibited the capacity of both suspensions to mount a T-cell response. However, addition of cis- UCA did not potentiate this UVB-induced immunosuppression. The eLC or pLC were then incubated with cis-UCA for 18 h at 37°C and washed before adding to allogeneic T cells. The obtained proliferative response was similar to that induced by control LC incubated in medium alone, demonstrating that pretreatment with cis -UCA did not alter human LC function. In conclusion, these results strongly suggest that cis-UCA has no direct effect on human LC antigen-presenting function.     

ADVENTITIOUS INTERCONVERSION OF cis- AND trans-UROCANIC ACID BY LABORATORY LIGHT

Urocanic acid (UCA) is a chromophore in the stratum corneum. Ultraviolet radiation (ultraviolet B) has been shown to suppress mammalian cell-mediated immunity. The photoisomerization of trans -UCA to cis -UCA was proposed as the initiator of the suppression process. Cis -urocanic acid has been demonstrated to suppress immunity by a variety of experiments. Investigators should be aware that laboratory illumination may be capable of interconverting trans -UCA and cis -UCA during experimental manipulations. This possible inadvertent contamination of one isomer by the other may influence results. We demonstrated that fluorescent lamps, daylight, sunlight and incandescent lamps were able to bring about isomerization. Window glass and container materials of plastic and clear glass did not filter out effective wavelengths, but three commercial plastic diffusers on fluorescent fixtures prevented the isomerization. Because the molar extinction coefficient (ɛ) for cis -UCA is less than that of trans -UCA, we have exposed 0.1 m M trans -UCA to ambient light and monitored the change in absorbance. A method is given to calculate the percentage of trans and cis isomers from the absorbance at 277 nm when the initial purity and absorbance are known. Using this procedure, we validated the molar extinction coefficient of cis -UCA.     

Pseudorotational analysis of 4-thiohexofuranose derivatives from H-H coupling constants

On the basis of Altona's empirical generalization of the Karplus equation, an expression of ³J_H,H as function of pseudorotation parameters for five-membered rings, was deduced. The resulting equation was parametrized by means of molecular mechanics calculations for tetrahydrofuran and tetrahydrothiophene. Estimation of ³J_H,H for the full pseudorotational itinerary was made. From the best fit between calculated and measured ³J_H,H values the preferred conformation of those rings may be established. The procedure was applied for the conformational analysis of 4-thiohexofuranose derivatives, having and β, -galacto and D- manno, and - -talo configurations.     

1,2-Shift of a Carboxyl Group in a Wagner-Meerwein Rearrangement

On treatment with HSO₃F in SO₂C1F at 0°, 3-hydroxy-2,2-dimethyl-3-phenyl-propionic acid ( 1a ) is transformed into 2-phenyl-3-methyl-2-butenoic acid ( 2a ) (isolated yield: 40–44%). Using monolabelled [3-¹³C]- 1a ( 1a *) and doubly labelled [1,3-¹³C₂]- 1a ( 1a **), the migration of HOOC (or a mechanistically equivalent group) was proved; a cross experiment established the intramolecular character of the rearrangement. By following the reaction at low temperature in an NMR. spectrometer, the formation of intermediates and side products was demonstrated.     

Metal Nanoparticles on Stainless Steel Surfaces as Novel Heterogeneous Catalysts

The goal of this work was the development of a novel type of heterogeneous catalyst, consisting of bare metal nanoparticles on stainless steel foils, which can be shaped to any kind of architecture and, if necessary, heated electrically. Solutions of pre-prepared, ligand protected and monodispersed gold, palladium, platinum and rhodium nanoparticles were sprayed onto stainless steel foils, followed by the careful removal of the ligand molecules by an oxygen plasma treatment. Due to this, bare particles become irreversibly fixed on the steel support. It could be shown that the original particle sizes do not change during the plasma treatment. Foils, densely coated with the nanoparticles, were used for gas phase catalyses in a self-made reactor at room temperature or at 60 °C. Hydrogenation of 1,3-butadiene at 15 nm Pd and 2 nm Pt, CO oxidation at 16 nm, 8 nm and 1.4 nm gold and NO reduction with NH₃ at 2 nm Rh particles were performed, indicating that the novel catalysts might in principle be applicable in technical processes if the experimental conditions like form and temperature would be optimized. Dedicated to Professor Dieter Fenske on the occassion of his 65th birthday.     

3-(Dimethylamino)-2,2-dimethyl-2H-azirin als α-Aminoisobuttersäure(Aib)-Äquivalent: Cyclische Depsipeptide durch direkte Amid-Cyclisierung

3-(Dimethylamino)-2,2-dimethyl-2H,-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amid Cyclization In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and α-hydroxycarboxylic acids react to give diamides of type 8 (Scheme 3). Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H₂O leads to the corresponding carboxylic acids 13 (Scheme 4). In toluene/Ph SH , phenyl thioesters of type 11 are formed (see also Scheme 5). Starting with diamides 8 , the formation of morpholin-2,5- diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11 (Scheme 3). Reaction of carboxylic acids with 1 , followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units (Scheme 4). Cyclization of 14a, 17a , and 20a with HCI in toluene at 100° gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18 , and 21 , respectively.     

A reinvestigation of asymmetric induction in diels-alder reactions to chiral acrylates.

The chiral induction in the Diels-Alder addition $\text{1}$ → $\text{2}$, assessed reliably by ¹⁹F-NMR-spectroscopy of the endo-esters $\text{4}$, varied between 47 - 93% in favor of the 2-(R)-adducts $\text{2}$ depending on the auxiliary chiral group and the Lewis-acid catalyst.     

1,6-dithia-spiro[4.4]nonadiene aus 2-thiazolin-5-thionen

4,4-Dimethyl-2-phenyl-2-thiazolin-5-thione ($\text{4}$) reacts with 2,3-diphenylcyclopropenone ($\text{2a}$) at 145°C and with benzonitrilio-2-propanide ($\text{6}$) at room temperature to yield the 1,6-dithia-spiro[4.4]nonadienes $\text{5}$ and $\text{7}$, respectively.     

Hexaruthenium carbonyl cluster complexes with basal edge-bridged square pyramidal metallic skeleton: efficient synthesis of 2-imidopyridine derivatives and determination of their reactive sites in carbonyl substitution reactions

The reactions of [Ru(3)(CO)(12)] with half equivalent of 2-amino-6-methylpyridine (H(2)ampy) or 2-aminopyridine (H(2)apy) in refluxing xylene give the hexanuclear products [Ru(6)(mu(3)-H)(2)(mu(5)-eta(2)-L)(mu-CO)(2)(CO)(14)] (L = ampy, 1; apy, 2). These reactions represent the first high-yield syntheses of hexanuclear complexes with a basal edge-bridged square pyramidal metallic skeleton. Five metal atoms of these complexes are bridged by the N-donor ligand in such a way that the edge-bridging metal atom is attached to the pyridine nitrogen, while the basal atoms of the square pyramid are capped by an imido fragment that arises from the activation of both N-H bonds of the NH(2) group. The reactive sites of these complexes in CO substitution reactions have been determined by studying the reactivity of 1 with triphenylphosphine. Two kinetically controlled monosubstitutions take place on the edge-bridging metal atom in positions cis to the pyridine nitrogen, leading to a mixture of two isomers of formula [Ru(6)(mu(3)-H)(2)(mu(5)-eta(2)-ampy)(mu-CO)(2)(CO)(13)(PPh(3))] (3 and 4). On heating at 80 degrees C, these monosubstituted isomers are transformed, via a dissociative pathway, into the product of thermodynamic control (5), which has the PPh(3) ligand on the apical Ru atom. The di- and trisubstituted derivatives [Ru(6)(mu(3)-H)(2)(mu(5)-eta(2)-ampy)(mu-CO)(2)(CO)(12)(PPh(3))(2)] (6) and [Ru(6)(mu(3)-H)(2)(mu(5)-eta(2)-ampy)(mu-CO)(2)(CO)(11)(PPh(3))(3)] (7) are stepwise formed from 3-5 and PPh(3). Compound 6 has the PPh(3) ligands on the edge-bridging and apical Ru atoms, and compound 7 has an additional PPh(3) ligand on an unbridged basal Ru atom. The compound [Ru(6)(mu(3)-H)(2)(mu(5)-eta(2)-ampy)(mu-CO)(2)(CO)(12)(mu-dppm)] (8), in which a basal and the apical Ru atoms are spanned by the dppm ligand, has been isolated from the reaction of 1 with bis(diphenylphosphino)methane.     

Carnitine in Pregnancy

Summary. By the 12^th week of gestation, mean whole blood and plasma carnitine levels are already significantly (p<0.01) lower than those of controls, with a further significant (p<0.01) decrease up to parturition. Diminished carnitine levels may cause a downregulation of carnitine palmitoyltransferase1 (CPT1), both the liver isoform (CPT1A) and muscle isoform (CPT1B), carnitine palmitoyltransferase2 (CPT2), and carnitine acetyltransferase (CRAT) in white blood cells of pregnant women, as determined by real time PCR using the LightCyclerSYBR Green technology.L-Carnitine-L-tartrate supplementation of 2 g/d resulted in an up to 10-fold increase of the relative mRNA abundances of CPT1B, CPT2, and OCTN2 and a 5-fold increase of CPT1A, and CRAT.There is a relationship between the relative mRNA levels of CPT1A and CPT1B and the FFA plasma levels. The substitution of 2 g L-carnitine-L-tartrate/d resulted in significant (p<0.001) lower FFA levels compared to untreated controls and the groups substituted with 0.5 and 1 g L-carnitine/d although plasma carnitine levels were not significantly increased. The most substantial effect was the reduced portion of acylcarnitines on total carnitine in those women receiving 2 g L-carnitine-L-tartrate.Carnitine substitution resulted in an enhanced excretion of both, free carnitine and acylcarnitines, whereas acetylcarnitine accounts for 50–65% of total acylcarnitines.The results of the present study provide evidence that L-carnitine supplementation in pregnancy in sufficient doses avoids a striking increase of plasma FFAs, which are thought to be the main cause of insulin resistance and consequently gestational diabetes mellitus (GDM).