Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract

Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.     

Synthese und Struktur der ersten Wasserfreien ternären Lithiumnitrate der Lanthanide,Li2[M(NO3)5] (M = La,Pr?Eu)

Synthesis and Structure of the First Anhydrous Ternary Lithium Nitrates of the Lanthanides, Li₂[M(NO₃)₅] (M = La, Pr? Eu). Single crystals of the ternary lithium nitrates of the lanthanides, Li₂[M(NO₃)₅] (M = La, Pr? Eu), are obtained by dissolving the respective anhydrous nitrate, previously obtained by dehydration of M(NO₃)₃ · 6 H₂O at 180°C under vacuum, in a melt of LiNO₃. In the crystal structure of Li₂[Pr(NO₃)₅] (orthorhombic, Pnnm, Z = 4, a = 899.6(2), b = 1 052.7(2), c = 1 178.6(2)pm; R = 0.072, R_w = 0.034) there are two crystallographically different Pr³⁺ ions, each surrounded by six bidentate nitrate ligands. One nitrate group is bridging between Pr1 and Pr2 resulting in a winded chain, [(O_2/2NO_2/1)Pr1(NO₃)₄(O_2/2NO_2/1)Pr2(O_2/2NO_2/1)(NO₃)₄]^5?, running along [010]. The chains are packed hexagonally and held together by lithium ions. The coordination polyhydron of Li⁺ may be described as a bicapped trigonal prism.     

On-line sheathless capillary electrophoresis/nanoelectrospray ionization-tandem mass spectrometry for the analysis of glycosaminoglycan oligosaccharides

A novel approach in glycosaminoglycomics, based on sheathless on-line capillary electrophoresis/nanoelectrospray ionization-quadrupole time of flight-mass spectrometry (CE/nanoESI-QTOF-MS) and tandem MS of extended chondroitin sulfate/dermatan (CS/DS) oligosaccharide chains is described. The methodology required the construction of a new sheathless CE/nanoESI-QTOF-MS configuration, its implementation and optimization for the high sensitivity analysis of CS/DS oligosaccharide mixtures from conditioned culture medium of decorin transfected human embryonic kidney (HEK) 293 cells. Under newly established sheathless on-line CE/(-)nanoESI conditions for glycosaminoglycan (GAG) ionization and MS detection, single CS/DS oligosaccharide components of extended chain length and increased sulfation degree were identified. Molecular ions corresponding to species carrying 5 and 6 negative charges could be generated for large GAG oligosaccharide species in the negative ion nanoESI-MS. The optimized on-line conditions enabled the detection of molecular ions assigned to oversulfated tetradeca-, octadeca-, and eicosasaccharide CS/DS molecules, which represent the category of largest sulfated GAG-derived oligosaccharides evidenced by CE/ESI-MS. By on-line CE/ESI tandem MS in data-dependent acquisition mode the oversulfated eicosasaccharide species could be sequenced and the localization of the additional sulfate group along the chain could be determined.     

Retention behaviour of 1,n-halo(alkylthio)alkanes in HPLC

The RPLC retention of 1,n-halo(alkylthio)alkanes on an ODS phase with methanol/water (95%/5%) has been investigated. Replacement of a methyl group in a dialkyl sulphide R-S-R by a halogen atom X, to yield the title compounds X-(CH₂)_n-S-R, generally results in a retention decrease. This retention loss results either from the halogen atom proper, or from its immediate vicinity, or from a reduced retention contribution of the alkyl units. The methylene groups (n) between halogen and sulphur produce somewhat greater retention than the methylene groups in the alkyl groups R.     

Spektroskopische und kristallographische Charakterisierung von [Cl3PNPCl3][MoOCl4] und die Kristallstruktur von [Cl3PNPCl3][MoCl6]

Spectroscopic and Crystallographic Characterization of [Cl₃PNPCl₃][MoOCl₄] and Crystal Structure of [Cl₃PNPCl₃][MoCl₆] [Cl₃PNPCl₃][MoCl₆] was obtained by reaction of MoCl₅ with [Cl₃PNPCl₃]Cl or [Cl₃PNPCl₃][PCl₆]. Its crystal was determined by X-ray diffraction (R = 0.072 for 889 observed reflexions). Lattice parameters: a = 811.9, b = 2086, c = 1016 pm, β = 101.7°, space group P2₁/c, Z = 4. The [Cl₃PNPCl₃]⁺ ions have a similar structure as in Cl₃PNPCl₃ [PCl₆] with PNP angles of 139°, but the crystal structures of the two compounds are not isotypic. Partial hydrolysis of [Cl₃PNPCl₃][MoCl₆] yields [Cl₃PNPCl₃][MoOCl₄] which forms green, very moisture sensitive crystals. X-ray diffraction patterns of [Cl₃PNPCl₃][MoOCl₄] single crystals exhibit planes of diffuse scattered radiation perpendicular to c^*, which show the presence of a two-dimensional disorder. Additional sharp reflexions correspond to an averaged structure with the lattice parameters a = 1598.4, b = 1141.2 and c = 415.1 pm, Z = 2, space group Pba2. Refinement of the averaged     

Formation of cyclic ions in the electron impact induced fragmentation of 1,n-bis-(alkylthio) alkanes

Fragmentation of molecular ions of 1,n-bis(alkylthio)alkanes (R¹-S-(CH₂)_n-S-R²) occurs mainly by α- or β-cleavage to a sulphur atom. The ratio of fragments derived by α- or β-cleavage depends on the number of methylene groups (n) between the two sulphur atoms and on the alkyl groups R¹ and R². Generally β-cleavage induced fragmentation dominates for 1,2-bis(alkylthio)ethanes (n=2) leading to formation of thiiranium ions. Fragmentations derived by α-cleavage are predominant for all compounds with n=3; base peaks corresponding to [M-(R)]⁺ or [M-(2R)+(H)]⁺ are found which gives evidence for formation of five membered cyclic ions. Such fragmenss are less intense in compounds with n=4 whereas m all other compounds β-cleavage predominates if R = methyl, ethyl, n-propyl.     

Stereochemical effects in electron impact mass spectra of cis-trans isomeric 1,2,4,5-tetramethylcyclohexanes

The mass spectrometric fragmentation of the five cis-trans isomeric 1,2,4,5-tetramethylcyclohexanes is influenced by their configuration. The thermochemically stable isomers show a higher abundance of the [M? CH₃]⁺ ions and a lower abundance of the [M? C₂H₅]⁺ ions than the strained isomers. The [M? CH₃]⁺/[M? C₂H₅]⁺ intensity ratio correlates with the enthalpy difference ΔH_isom and with the mean number of gauche arrangements Z_g^I of the stereoisomers.     

What a Difference an OH Makes: Conformational Dynamics as the Basis for the Ligand Specificity of the Neomycin‐Sensing Riboswitch

To ensure appropriate metabolic regulation, riboswitches must discriminate efficiently between their target ligands and chemically similar molecules that are also present in the cell. A remarkable example of efficient ligand discrimination is a synthetic neomycin‐sensing riboswitch. Paromomycin, which differs from neomycin only by the substitution of a single amino group with a hydroxy group, also binds but does not flip the riboswitch. Interestingly, the solution structures of the two riboswitch–ligand complexes are virtually identical. In this work, we demonstrate that the local loss of key intermolecular interactions at the substitution site is translated through a defined network of intramolecular interactions into global changes in RNA conformational dynamics. The remarkable specificity of this riboswitch is thus based on structural dynamics rather than static structural differences. In this respect, the neomycin riboswitch is a model for many of its natural counterparts.     

Strictosidine synthase: mechanism of a Pictet-Spengler catalyzing enzyme

The Pictet-Spengler reaction, which yields either a beta-carboline or a tetrahydroquinoline product from an aromatic amine and an aldehyde, is widely utilized in plant alkaloid biosynthesis. Here we deconvolute the role that the biosynthetic enzyme strictosidine synthase plays in catalyzing the stereoselective synthesis of a beta-carboline product. Notably, the rate-controlling step of the enzyme mechanism, as identified by the appearance of a primary kinetic isotope effect (KIE), is the rearomatization of a positively charged intermediate. The KIE of a nonenzymatic Pictet-Spengler reaction indicates that rearomatization is also rate-controlling in solution, suggesting that the enzyme does not significantly change the mechanism of the reaction. Additionally, the pH dependence of the solution and enzymatic reactions provides evidence for a sequence of acid-base catalysis steps that catalyze the Pictet-Spengler reaction. An additional acid-catalyzed step, most likely protonation of a carbinolamine intermediate, is also significantly rate controlling. We propose that this step is efficiently catalyzed by the enzyme. Structural analysis of a bisubstrate inhibitor bound to the enzyme suggests that the active site is exquisitely tuned to correctly orient the iminium intermediate for productive cyclization to form the diastereoselective product. Furthermore, ab initio calculations suggest the structures of possible productive transition states involved in the mechanism. Importantly, these calculations suggest that a spiroindolenine intermediate, often invoked in the Pictet-Spengler mechanism, does not occur. A detailed mechanism for enzymatic catalysis of the beta-carboline product is proposed from these data.     

Synthesis of new N-analogous corollosporine derivatives with antibacterial activity by laccase-catalyzed amination

Corollosporine isolated from the marine fungus Corollospora maritima and N-analogous corollosporines are antimicrobial substances. Owing to the basic structure of the N-analogous corollosporines, they have become an attractive target for laccase-catalyzed derivatisation. In this regard we report on the straightforward laccase-catalyzed amination of dihydroxylated arenes with N-analogous corollosporines. In biological assays the obtained amination products are more active than the parent compounds.