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Coca-paste (CP) is a drug of abuse that so far has not been extensively characterized. CP is an intermediate product of the cocaine alkaloid extraction process from coca leaves, hence it has a high content of cocaine base mixed with other chemical substances (impurities) and it is probably adulterated when it reaches the consumers. Despite its high prevalence and distribution through South America, little is known about its effects on the central nervous system. In the present study, a chemical analysis of CP samples from different police seizures was performed to determine the cocaine base content and the presence and content of impurities and adulterants. Some CP representative samples were selected to study the effects on the locomotor activity induced after acute systemic administration in rats as a measure of its stimulant action. The behavioral response was compared to equivalent doses of cocaine. As expected, cocaine was the main component in most of the CP samples assayed. Caffeine was the only active adulterant detected. Interestingly, several CP samples elicited a higher stimulant effect compared to that observed after cocaine when administered at equivalent doses of cocaine base. Combined treatment of cocaine and caffeine, as surrogate of different CP samples mimicked their stimulant effect. We demonstrated that cocaine and caffeine are the main components responsible for the CP-induced stimulant action while the contribution of the impurities was imperceptible., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Attempts to prepare mixed-ligand zinc-zinc-bonded compounds that contain bulky C(5)Me(5) and terphenyl groups, [Zn(2)(C(5)Me(5))(Ar')], lead to disproportionation. The resulting half-sandwich Zn(II) complexes [(η(5)-C(5)Me(5))ZnAr'] (Ar' = 2,6-(2,6-(i)Pr(2)C(6)H(3))(2)-C(6)H(3), 2; 2,6-(2,6-Me(2)C(6)H(3))(2)-C(6)H(3), 3) can also be obtained from the reaction of [Zn(C(5)Me(5))(2)] with the corresponding LiAr'. In the presence of pyr-py (4-pyrrolidinopyridine) or DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), [Zn(2)(η(5)-C(5)Me(5))(2)] reacts with C(5)Me(5)OH to afford the tetrametallic complexes [Zn(2)(η(5)-C(5)Me(5))L(μ-OC(5)Me(5))](2) (L = pyr-py, 6; DBU, 8), respectively. The bulkier terphenyloxide Ar(Mes)O(-) group (Ar(Mes) = 2,6-(2,4,6-Me(3)C(6)H(2))(2)-C(6)H(3)) gives instead the dimetallic compound [Zn(2)(η(5)-C(5)Me(5))(OAr(Mes))(pyr-py)(2)], 7, that features a terminal Zn-OAr(Mes) bond. DFT calculations on models of 6-8 and also on the Zn-Zn-bonded complexes [Zn(2)(η(5)-C(5)H(5))(OC(5)H(5))(py)(2)] and [(η(5)-C(5)H(5))ZnZn(py)(3)](+) have been performed and reveal the nonsymmetric nature of the Zn-Zn bond with lower charge and higher participation of the s orbital of the zinc atom coordinated to the cyclopentadienyl ligand with respect to the metal within the pseudo-ZnL(3) fragment. Cyclic voltammetric studies on [Zn(2)(η(5)-C(5)Me(5))(2)] have been also carried out and the results compared with the behavior of [Zn(C(5)Me(5))(2)] and related magnesium and calcium metallocenes., (© 2011 American Chemical Society)

Background: The rs738409 C→G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease., Objective: We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity., Design: We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([(2)H(5)]glycerol infusion) were measured before and after the diet., Results: At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 ± 0.5 kg; PNPLA3-148II: -3.1 ± 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01)., Conclusion: Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775.

The title compound, C(15)H(30)N(2) (2+)·2Br(-)·H(2)O, was synthesized by reaction of 4-piperidino-piperidine with dibromo-pentane. The dication is built up from three linked piperidine rings, two of which have one quaternary N atom in common (azoniaspiro), whereas the third is N-C bonded to the azoniaspiro system and protonated on the N atom (piperidinium). All three piperidine rings adopt chair conformations. The crystal structure features O-H⋯Br and N-H⋯Br hydrogen bonds.

Three new benzodihydrofurans (1-3) and seven known aromatic compounds (4-10) were isolated from the roots of Cyperus teneriffae. Vibrational circular dichroism spectroscopy was used to define the absolute configuration of 1.

We report the synthesis of the hitherto unknown zwitterionic alkoxyamino cyanoboranes by reduction of O-alkyloximes with sodium cyanoborohydride; unprecedented cyanoboronated N-alkoxyformamidines were also isolated as by-products. Boronated alkoxyamines were found to be efficient cyanoborane transfer agents towards more basic amines, including aminosugars; they were also successfully transformed into neoglycoconjugates by the neoglycorandomization reaction with reducing sugars., (© The Royal Society of Chemistry 2011)

Biphasic catalytic olefin epoxidation systems consisting of oxodiperoxomolybdenum catalysts in 1-n-alkyl-3-methylimidazolium hexafluorophosphate ionic liquid (IL) media with aqueous hydrogen peroxide oxidant were optimised by tuning the molecular structure of the IL and employing N-heterocyclic donor base additives to inhibit hydrolysis and enhance the activity of the catalyst. The latter study was only made possible by the solubilising properties of the IL media. Of the bases investigated, pyrazoles were identified as the most efficient additive species and the best results were obtained using 3,5-dimethylpyrazole. Immobilisation of the catalyst in the IL allowed for very efficient catalyst recycling. Finally, the compound [MoO(O(2))(2)(3-Mepz)(2)] (3-Mepz = 3-methylpyrazole) was characterised and its structure determined by X-ray crystallography.

Gas phase skeletal rearrangements of regioisomeric 3-cyano-2-methoxy-3a-alkylfuro[2,3-b]- and [3,2-b]indoles were evidenced by product ions [M-32](+•), consistent with loss of methanol, on electron ionization in their mass spectra. The rearranged products occurring in gas phase were demonstrated to have elemental composition and fragmentation properties identical to those of authentic samples of 2-indolyl cyanomalonates. Isotopic labeling experiments support the formation mechanism of the [M-32](+•) ion. Additional thermal gas-phase reaction products were characterized by comparison with an authentic sample., (Copyright © 2011 John Wiley & Sons, Ltd.)

This communication highlights the need of building hierarchical digraphs for the unequivocal assignment of stereochemical descriptors of (-)-myrtenal, a naturally-occurring oxygenated monoterpene whose absolute configuration (AC) is sometimes misrepresented in its structural formulae. Differentiation between duplicated atoms and phantom atoms for the proper application of the sequence rules is shown to be an essential step to get a proper construction of hierarchical digraphs.

Experimental as well as theoretical studies have been carried out with the aim of elucidating the mechanism of the atom transfer radical addition (ATRA) of styrene and carbon tetrachloride with a Tp(x)Cu(NCMe) complex as the catalyst precursor (Tp(x) = hydrotrispyrazolyl-borate ligand). The studies shown herein demonstrate the effect of different variables in the kinetic behavior. A mechanistic proposal consistent with theoretical and experimental data is presented.

The reaction of 1-alkynes with acyl azides in the presence of [Tpm(*,Br)Cu(NCMe)]BF(4) [Tpm(*,Br) = tris(3,5-dimethyl-4-bromopyrazolyl)methane] as the catalyst provides 2,5-oxazoles in moderate to high yields. This is a novel transformation of the CuAAC type that constitutes a significant variation of the commonly observed [3 + 2] cycloaddition reaction to yield 1,2,3-triazoles.

Well-defined dimeric or polymeric Pd(0) complexes [Pd(μ-(iPr)PCHP)](n) (n = 2 or ∞) containing the bridging ligand α,α'-bis(diisopropylphosphino)-m-xylene ((iPr)PCHP) are produced under mild conditions when the cyclometallated PCP pincer complex ((iPr)PCP)Pd-OH reacts with methanol or isopropanol.

Manganese alkyl complexes stabilised by 2,6-bis(N,N'-2,6-diisopropyl-phenyl)acetaldiminopyridine ((iPr)BIP) have been selectively prepared by reacting suitable alkylmanganese(II) precursors, such as homoleptic dialkyls [(MnR(2))(n)] or the corresponding THF adducts [{MnR(2)(thf)}(2)] with the mentioned ligand. For R=CH(2)CMe(2)Ph or CH(2)Ph, formally Mn(I) derivatives are produced, in which one of the two R groups migrates to the 4-position of the central pyridine ring in the (iPr)BIP ligand. In contrast, a true dialkyl complex [MnR(2)((iPr)BIP)] can be isolated for R=CH(2)SiMe(3). In solution, this compound slowly evolves to the corresponding Mn(I) monoalkyl derivative. A detailed study of this reaction provides insights on its mechanism, showing that it proceeds through successive alkyl migrations, followed by spontaneous dehydrogenation. Protonation of [Mn(CH(2)SiMe(3))(2)((iPr)BIP)] with the pyridinium salt [H(Py)(2)][BAr'(4)] (Ar'=3,5-C(6)H(3)(CF(3))(2)) leads to the cationic species [Mn(CH(2)SiMe(3))(Py)((iPr)BIP)](+). Alternatively, the same complex can be produced by reaction of the pyridine complex [{Mn(CH(2)SiMe(3))(2)(Py)}(2)] with the protonated ligand salt [H(iPr)BIP](+)[BAr'(4)](-). This last reaction allows the synthesis of analogous cationic alkylmanganese(II) derivatives, when precursors of type [MnR(2)((iPr)BIP)] are not available. Treatment of these neutral and cationic (iPr)BIP alkylmanganese derivatives with a range of typical co-catalysts (modified methylaluminoxane (MMAO), B(C(6)F(5))(3), trimethyl or triisobutylaluminum) does not lead to active ethylene polymerisation catalysts.

The synthesis and structural characterization of a mixed-sandwich (η(5)-C(5)Me(5))Rh(III) complex of the cyclometalated phosphine PMeXyl(2) (Xyl = 2,6-C(6)H(3)Me(2)) with unusual κ(4)-P,C,C',C'' coordination (compound 1-BAr(f); BAr(f) = B(3,5-C(6)H(3)(CF(3))(2))(4)) are reported. A reversible κ(4) to κ(2) change in the binding of the chelating phosphine in cation 1(+) induced by dihydrogen and hydrosilanes triggers a highly efficient Si-H/Si-D (or Si-T) exchange applicable to a wide range of hydrosilanes. Catalysis can be carried out in an organic solvent solution or without solvent, with catalyst loadings as low as 0.001 mol %, and the catalyst may be recycled a number of times.

The N(2)-donor bidentate ligands di(1H-indazol-1-yl)methane (L(1)) and di(2H-indazol-2-yl)methane (L(2)) (L in general) have been synthesized, and their coordination behavior toward Zn(II), Cd(II), and Hg(II) salts has been studied. Reaction of L(1) and L(2) with ZnX(2) (X = Cl, Br, or I) yields [ZnX(2)L] species (1-6), that, in the solid state, show a tetrahedral structure with dihapto ligand coordination via the pyrazolyl arms. The reaction of L(1) and L(2) with Zn(NO(3))(2)·6H(2)O is strongly dependent on the reaction conditions and on the ligand employed. Reaction of L(1) with equimolar quantities of Zn(NO(3))(2)·6H(2)O yields the neutral six-coordinate species [Zn(NO(3))(2)(L(1))], 7. On the other hand the use of L(1) excess gives the 2:1 adduct [Zn(NO(3))(2)(L(1))(2)], 8 where both nitrates act as a unidentate coordinating ligand. Analogous stoichiometry is found in the compound obtained from the reaction of L(2) with Zn(NO(3))(2)·6H(2)O which gives the ionic [Zn(NO(3))(L(2))(2)](NO(3)), 10. Complete displacement of both nitrates from the zinc coordination sphere is observed when the reaction between L(1) excess and the zinc salt was carried out in hydrothermal conditions. The metal ion type is also determining structure and stoichiometry: the reaction of L(2) with CdCl(2) gave the 2:1 adduct [CdCl(2)(L(2))(2)] 11 where both chlorides complete the coordination sphere of the six-coordinate cadmium center; on the other hand from the reaction of L(1) with CdBr(2) the polynuclear [CdBr(2)(L(1))](n) 12 is obtained, the Br(-) anion acting as bridging ligands in a six-coordinate cadmium coordination environment. The reaction of L(1) and L(2) with HgX(2) (X = Cl, I, SCN) is also dependent on the reaction conditions and the nature of X, two different types of adducts being formed [HgX(L)] (14: L = L(1), 16, 17: L = L(1) or L(2), X = I, 19: L = L(2), X = SCN) and [HgX(L)(2)] (15: L = L(2), X = Cl, 18: L = L(1), X = SCN). The X-ray diffraction analyses of compounds 1, 2, 4, 5, 7, 8, 10-12, 14, 15, and 19 are also reported. The variations of the coordination geometry parameters in the complexes are compared and discussed.

The complex [Mo(4)O(16)(dmpz)(6)] (1) has been isolated as part of a study of oxodiperoxomolybdenum catalysed epoxidation of olefin substrates with hydrogen peroxide in ionic liquids. Notably, 1 is the first dioxoperoxomolybdenum species to be structurally characterised.

The unit cell of the title compound, poly[[μ-aqua-μ-hydroxido-di-μ-oxalato-chromium(III)disodium] monohydrate], {[CrNa(2)(C(2)O(4))(2)(OH)(H(2)O)]·H(2)O}(n), contains four [Na1(μ-H(2)O)Na2][(C(2)O(4))(2)Cr(μ-OH)·H(2)O] formula units, each of which consists of two crystallographically independent Na(+) sites (bridged by one aqua ligand), one half of a centrosymmetric di-μ-hydroxido-bis-[cis-bis-(oxalato)chromate(III)] dimer, [(C(2)O(4))(2)Cr(μ-OH)(2)Cr(C(2)O(4))(2)](4-), and one uncoordin-ated water mol-ecule. The structure is best described as a coordination polymer in which the three-dimensional lattice framework is realized by the inter-connection of the metallic atoms via the O atoms of the aqua, hydroxide and oxalate ligands. One Na atom is hepta-coordinated by one water, one hydroxide and five oxalate O atoms, whilst the other is penta-coordinated by one water and four oxalate O atoms. The coordination around the Cr(3+) sites is pseudo-octa-hedral, involving four aqua and two hydroxide O atoms. Adjacent Na atoms are separated by 3.593 (2) Å, whereas the intra-dimer Cr⋯Cr spacing is 2.978 (1) Å. The crystal structure is consolidated by extended relatively weak O-H⋯O hydrogen bonding with O⋯O distances ranging from 2.808 (4) to 3.276 (5) Å.

The VCD spectrum of the monoterpene (-)-myrtenal (1) was compared with theoretical spectra using ab initio density functional theory (DFT) calculations at the B3LYP/6-31G(d,p), B3LYP/6-31G+(d,p), B3LYP/6-311G+(d,p), B3LYP/DGDZVP, and B3PW91/DGTZVP levels of theory. Conformational analysis of 1 indicated that the lowest energy conformer was s-trans-C2-C10, which contributes more than 98.5% to the total conformational population regardless of the employed level of theory. The use of a recently developed confidence level algorithm demonstrated that VCD spectra calculated for the main conformer, using the indicated hybrid functionals and basis set, gave no significant changes, from where it follows that B3LYP/DGDZVP calculations provide a superior balance between computer cost and VCD spectral accuracy. The DGDZVP basis set demanded around a quarter the time than the 6-311G+(d,p) basis set while providing similar results. The spectral comparison also provided evidence that the levorotatory enantiomer of myrtenal has the 1R absolute configuration., (2010 Elsevier Ltd. All rights reserved.)

The absolute configuration (AC) of 6beta-hydroxy-3alpha-senecioyloxytropane (1), 3alpha-hydroxy-6beta-tigloyloxytropane (2), 3alpha-hydroxy-6beta-senecioyloxytropane (3), and 3alpha-hydroxy-6beta-angeloyloxytropane (4) was assigned as (1R,3R,5S,6R) using density functional theory (DFT) calculations at the B3LYP/DGDZVP level of theory in combination with experimental vibrational circular dichroism (VCD) measurements and comparison with the spectra of similar tropanes. The AC of 1 followed from a sample isolated from Schizanthus grahamii, while those of the mixture of 2 and 3, isolated from the same source, were determined by comparing the VCD measurement to a weighted calculation of the individual VCD spectra according to a 69:31 ratio of 2:3 determined by (1)H NMR signal integration. In turn, Schizanthus pinnatus provided a 7:3 mixture of 1:4 whose AC was determined using the experimental VCD absorptions in the 1150-950 cm(-1) spectral region which were compared with those observed for 1-3 and with those described for other 3alpha,6beta-tropanediol derivatives., (Copyright 2010 Elsevier Ltd. All rights reserved.)

A novel transformation in which mono- or dialkyl-substituted furans are converted into 1,2-dihydropyridines upon reaction with PhI horizontal lineNTs at room temperature is reported. The reaction is catalyzed by complexes of general formula Tp(x)M (M = Cu, Ag) and consists of a one-pot procedure with four consecutive catalytic cycles. Furan aziridination is followed by aziridine ring-opening, transimination reaction, inverse-electronic-demand aza-Diels-Alder reaction, and a final hydrogen elimination reaction. The mechanism of the overall transformation is proposed where the metal complex displays a crucial role along the reaction pathway.

Background: The human umbilical cord contains mucoid connective tissue and fibroblast-like cells. These cells named Wharton's jelly cells, (WJCs) display properties similar to mesenchymal stem cells therefore representing a rich source of primitive cells to be potentially used in regenerative medicine., Results: To better understand their self-renewal and potential in vitro expansion capacity, a reference 2D map was constructed as a proteomic data set. 158 unique proteins were identified. More than 30% of these proteins belong to cytoskeleton compartment. We also found that several proteins including Shootin1, Adenylate kinase 5 isoenzyme and Plasminogen activator-inhibitor 2 are no longer expressed after the 2nd passage of in vitro replication. This indicates that the proliferative potency of these cells is reduced after the initial stage of in vitro growing. At the end of cellular culturing, new synthesized proteins, including, ERO1-like protein alpha, Aspartyl-tRNA synthetase and Prolyl-4-hydroxylase were identified. It is suggested that these new synthesized proteins are involved in the impairment of cellular surviving during replication and differentiation time., Conclusions: Our work represents an essential step towards gaining knowledge of the molecular properties of WJCs so as to better understand their possible use in the field of cell therapy and regenerative medicine.

The polyoxygenated longipinane derivatives 1- 8 were tested as antifeedant compounds against the herbivorous insects Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae. Compounds 1-3 and 8 exhibited significant antifeedant activity against S. littoralis and M. persicae. The antifeedant activity against S. littoralis increased moderately after the C-8 hydroxy group in 3 was removed to afford 1 and increased strongly after the remaining two hydroxy groups were acetylated to afford 2. Compound 1 was active on M. persicae. Compounds 1, 3, and 4, with an unsaturated six-membered ring, exhibited an increase in post-ingestive effects on S. littoralis ranging from antifeedant in the case of 1 to toxic for compounds 3 and 4. These compounds did not have any phytotoxic effect on Lactuca sativa. When tested on a panel of tumoral cells, compounds 2 and 6 exhibited moderate selective cytotoxic effects on the p53 null lung carcinoma cells H1299, which were not affected by the drug paclitaxel. In addition, vibrational circular dichroism (VCD) was applied to the representative longipinene derivative 2 to verify its absolute configuration, and the sensitivity of the VCD methodology was evaluated by comparing spectra of the three diastereoisomers (4 R,5 S,7 R,9 R,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one (2), (4 R,5 S,7 S,9 R,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one, and (4 R,5 S,7 R,9 S,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one., (Georg Thieme Verlag KG Stuttgart-New York.)

Mesenchymal stem cells (MSCs) are of special interest as therapeutic agents in the settings of both chronic inflammatory and autoimmune diseases. Toll-like receptors (TLR) ligands have been linked with the perpetuation of inflammation in a number of chronic inflammatory diseases due to the permanent exposure of the immune system to TLR-specific stimuli. Therefore, MSCs employed in therapy can be potentially exposed to TLR ligands, which may modulate MSC therapeutic potential in vivo. Recent results demonstrate that MSCs are activated by TLR ligands leading to modulation of the differentiation, migration, proliferation, survival, and immunosuppression capacities. However inconsistent results among authors have been reported suggesting that the source of MSCs, TLR stimuli employed or culture conditions play a role. Notably, activation by TLR ligands has not been reported to modulate the "immunoprivileged" phenotype of MSCs which is of special relevance regarding the use of allogeneic MSC-based therapies. In this review, we discuss the available data on the modulation of MSCs activity through TLR signalling.

An efficient route to a new family of axially chiral biaryl ligands by a Suzuki-Miyaura cross-coupling reaction between ortho,ortho'-disubstituted aryl iodides bearing in ortho position a tert-butyl or p-tolylsulfinyl group and ortho-substituted phenyl boronic acids or esters is described. The comparison between the t-BuSO and p-TolSO groups as chiral controllers is reported. The modularity of the approach is demonstrated by the preparation of a variety of enantiopure axially chiral mixed S/N and S/P ligands.

Efficient methodologies for the synthesis of regioisomeric 3-pyrrolines by reaction of electron-deficient imines and sulfur-containing allenyl derivatives are presented. Lithiated thioallenes give 2-aryl-3-phenylsulfonyl-3-pyrrolines, whereas allenyl sulfones furnish the isomeric 2-aryl-4-phenylsulfonyl-3-pyrrolines through migration of the sulfonyl group that catalyzes the nucleophilic [3 + 2] cycloaddition.

Enantiomerically pure (1S,4S)-(-)-3-oxo-1,8-cineole (-)-2 and (1R,4R)-(+)-3-oxo-1,8-cineole (+)-2 were prepared for the first time and their absolute configurations assigned by vibrational circular dichroism (VCD) measurements. Thus, treatment of cineole 1 with chromyl acetate gave rac-2 which after sodium borohydride reduction and acetylation provided racemic 3-endo-acetyloxy-1,8-cineole, rac-4. Enantioselective hydrolysis using porcine liver esterase (PLE) gave a mixture of 3-endo-hydroxy-1,8-cineole (-)-3 and 3-endo-acetyloxy-1,8-cineole (+)-4. After chromatographic separation, (-)-3 was oxidized to (+)-2, while (+)-4 was hydrolysed to (+)-3 and then oxidized to (-)-2. The absolute configuration of either ketone 2 was established by VCD spectroscopy in combination with density functional theory (DFT) calculations at the B3LYP/DGDZVP level of theory, from where it followed that the (+)-2 enantiomer corresponds to (1R,4R)-1,3,3-trimethyl-5-oxo-2-oxabicyclo[2.2.2]octane and the (-)-2 enantiomer to the (1S,4S) molecule which is also in agreement with the absolute configuration deduced by the Mosher method for the starting chiral alcohols. Some literature inconsistencies are clarified. In addition, the enantiomerically pure monoester (1S,3S,4R,5R)-(-)-3-acetyloxy-5-hydroxy-1,8-cineole 6 and the ketoester (1R,3S,4R)-(+)-3-acetyloxy-5-oxo-1,8-cineole 7 were prepared from meso-diacetate 5 by enantioselective asymmetrization also using PLE.

Neutral, C2-symmetric S/C/S ligands based on N-heterocyclic carbenes and thioether functionalities were incorporated into transition metal complexes characterised by two direct metal-stereogenic sulfur bonds. This new ligand design was applied to 1,3-dipolar cycloadditions as the first example of the use silver of carbenes in asymmetric catalysis.

Thermal activation of terpyridine in the presence of an unsaturated Ir(III) fragment stabilized by a hydrotris(pyrazolyl) borate ligand gives rise to mononuclear complex and binuclear , in which the polypyridine behaves, respectively, as a mono- or a bi-dentate N-heterocyclic carbene.

Human adipose-derived mesenchymal stem cells (hASCs) are mesenchymal stem cells (MSCs) with reduced immunogenicity and capability to modulate immune responses. Whereas the immunosuppressive activity of bone marrow-MSCs has received considerable attention during the last few years, the specific mechanisms underlying hASC-mediated immunosuppression have been poorly studied. Recent studies comparing both cell types have reported differences at transcriptional and proteomic levels, suggesting that hASCs and bone marrow-MSCs, while having similarities, are quite different. This suggests that different mechanisms of immunosuppression may apply. Here, we report that hASCs inhibit peripheral blood mononuclear cells (PBMCs), and CD4(+) and CD8(+) T cell proliferation in both cell-cell contact and transwell conditions, which is accompanied by a reduction of proinflammatory cytokines. We demonstrate that hASCs do not constitutively express immunomodulatory factors. Conditioned supernatants from hASCs stimulated by IFN-gamma, PBMCs, or activated PBMCs highly inhibited PBMC proliferation, indicating that inhibitory factors are released upon hASC activation. Many factors have been involved in MSC-mediated immunosuppression, including IFN-gamma, IL-10, hepatocyte growth factor, prostaglandin E2, transforming growth factor-beta1, indoleamine 2,3-dioxygenase (IDO), nitric oxide, and IL-10. Using pharmacological inhibitors, neutralizing antibodies, and genetically modified hASCs that constitutively express or silence IDO enzyme, we demonstrate that, in the case of hASCs, the IFN-gamma/IDO axis is essential. Taken together, our data support the key role of IDO in the therapeutic use of hASC on immunomediated diseases.

The reaction of [1,2,4]triazolo[4,3-a]pyridinium tetrafluoroborates with [RhCl(COD)](2) and [PdCl(allyl)](2) takes place under mild basic conditions (Et(3)N, THF, room temperature) to afford the corresponding [RhCl(COD)(Tripy)] and [PdCl(allyl)(Tripy)] complexes, respectively (Tripy = [1,2,4]triazolo[4,3-a]pyridin-3-ylidene), and their structures were analysed by X-ray diffractometry and spectroscopic techniques. The sigma-donor ability of the new ligands was estimated by comparative analysis of infrared nu(CO) stretching frequencies of [RhCl(CO)(2)(Tripy)] complexes, and proved to be strongly dependent on the substitution pattern. Additionally, a first insight into the catalytic properties of the latter in the Suzuki-Miyaura cross coupling demonstrates a good catalytic activity that enables the coupling of aryl chlorides at room temperature.

Novel synthetic routes for the preparation of trinuclear copper(I) complexes with triscarbene ligands are presented, which yield higher purity products than the one previously described. The first crystal structure of one of these complexes is reported and confirms the expected structure. The trinuclear complexes proved to be efficient catalysts of Ullmann-type reactions as well as of the Sonogashira reaction.

Reaction of the Ir(III) complex [(Tp(Me2))Ir(C(6)H(5))(2)(N(2))] (1N(2)) with ortho-cresol (2-methylphenol) occurs with cleavage of the O-H and two C(sp(3))-H bonds of the phenol and formation of the electrophilic hydride alkylidene derivative [(Tp(Me2))Ir(H){=C(H)C(6)H(4)-o-O}] (2). The analogous reaction of 2-ethylphenol gives a related product 3. Both 2 and 3 have been shown to be identical to the minor, unidentified products of the already reported reactions of 1 with anisole and phenetole, respectively. Thus, in addition to the route that leads to the known heteroatom-stabilized hydride carbene [(Tp(Me2))Ir(H){=C(H)OC(6)H(4)-o-}] (B), anisole can react with 1 with cleavage of the O-CH(3) bond and formation of a new carbon-carbon bond. In contrast, only C-H bond-activation products with structures akin to B result from 1N(2) and 3,5-dimethylanisole (complex 8) or 4-fluoroanisole (9). Using anisole as a model, a computational study of the triple C-H bond activation (two aliphatic C-H bonds plus an ortho-metalation reaction) that is responsible for the formation of these heteroatom-stabilized hydride carbenes has been undertaken.

The one-pot conversion of readily available alpha-amino acid into beta-amino acid derivatives was carried out in good yields. The method is a sequential process initiated by a tandem radical decarboxylation-oxidation reaction; the resulting acyliminium ion was trapped by silyl ketenes. Stoichiometric and catalytic versions of this reaction were developed and then applied to prepare modified di- and tripeptides. Interestingly, some tripeptides formed expanded beta-turns in the solid state.

Human adipose-derived stem cells (hASCs) are mesenchymal stem cells with reduced immunogenicity and the capability to modulate immune responses. These properties make hASCs of special interest as therapeutic agents in the settings of chronic inflammatory and autoimmune diseases. Exogenous and endogenous toll-like receptor (TLR) ligands have been linked with the perpetuation of inflammation in a number of chronic inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis because of the permanent exposure of the immune system to TLR-specific stimuli. Therefore, hASCs employed in therapy are potentially exposed to TLR ligands, which may result in the modulation of hASC activity and therapeutic potency. In this study, we demonstrate that hASCs possess active TLR2, TLR3, and TLR4, because activation with specific ligands resulted in induction of nuclear factor kappa B-dependent genes, such as manganese superoxide dismutase and the release of interleukin (IL)-6 and IL-8. TLR3 and TLR4 ligands increased osteogenic differentiation, but no effect on adipogenic differentiation or proliferation was observed. Moreover, we show that TLR activation does not impair the immunogenic and immunosuppressive properties of hASCs. These results may have important implications with respect to the safety and efficacy of hASC-based cell therapies.

Nonpolar and medium polarity fractions from whole plant methanolic extracts of Stevia monardifolia afforded the new 7beta-angeloyloxy-8alpha-isovaleroyloxylongipin-2-en-1-one 1 along with known 7beta,8alpha-diangeloyloxylongipin-2-en-1-one 2 and 7beta,8alpha-diangeloyloxylongipinan-1-one 3. Alkaline hydrolysis of a mixture of 1 and 2 gave 7beta,8alpha-dihydroxylongipin-2-en-lone 4 which was subjected to a single crystal X-ray diffraction study. The new compound 1, which is the third 7beta,8alpha-dihydroxylongipin-2-en-1-one diester natural product isolated from a Stevia especies, was fully characterized by one- and two-dimensional NMR spectroscopy and its absolute configuration was confirmed as the 4R,5S,7S,8S,10R,11R enantiomer by vibrational circular dichroism (VCD) measurements in comparison to calculation at the B3LYP/DGDZVP level of theory.

Two new neutral hexacoordinated silicon complexes with SiN(4)O(2) (6) and SiN(3)O(2)C (7) coordinating frameworks were synthesized by reaction of the O,N,N,O-donor salen-type ligand 1,2-bis[[(2-hydroxy-4-methoxyphenyl)(phenyl)methylene]amino]ethane (H(2)salen*) with Si(NCS)(4) and HMeSi(NCS)(2), respectively. The complexes 6 [Si(salen*)(NCS)(2)] and 7 [Si(salen*)Me(NCS)] were studied in the solid-state by (29)Si and (15)N CP/MAS NMR and in solution by (1)H, (13)C, and (29)Si insensitive nuclei enhanced by polarization transfer (INEPT) NMR, UV/vis and FT-IR spectroscopy. Elemental analysis and single-crystal X-ray diffraction analysis were used to confirm the composition and structure for compounds 6 and 7. Both complexes contain the dianionic salen-type ligand coordinated in an equatorial fashion to the silicon center, while the axial positions are occupied by two thiocyanato-N ligands for 6 and one thiocyanato-N and one methyl ligand for 7. Complex 6, which contains two Si-NCS functional groups, was used as monomer to produce a mixture of linear oligosilanes with a hexacoordinated silicon backbone (formulated SCN-[Si(salen*)](n)-NCS, n = 2-8) 8, via a Wurtz-type coupling reaction. Oligomers 8 were identified by solid-state (29)Si cross polarization-magic angle spinning NMR and solution (1)H and (29)Si NMR spectroscopy, matrix assisted laser desorption ionization-time of flight (MALDI-TOF), gel-permeation chromatography (GPC), FT-IR, UV/vis spectroscopy and thermogravimetric analysis (TGA). Conclusive evidence of the oligomeric nature of 8 was provided by MALDI-TOF spectrometry and was supported by quantitative solution (29)Si NMR and GPC studies.

Three alternative synthetic routes for the synthesis of naturally occurring n-butyl (5-formylfuran-2-yl)methyl succinate (1) are described. One of them started from furfuryl alcohol (4), and the other two synthetic strategies started from 5-(hydroxymethyl)furfural (6), which could be readily obtained from D-fructose. One of the latter involved a two-step reaction sequence: esterification of 6 with succinic anhydride (5) and esterification of the resultant mono-succinate 2 with n-butyl bromide, to give 1 in 85% overall yield. The second, a one-pot two-step synthesis, consisted of treating 6 with 5 followed by the addition of n-butyl bromide to afford the desired natural product 1 in 85% yield.

New zincocenes [ZnCp'(2)] (2-5) with substituted cyclopentadienyl ligands C(5)Me(4)H, C(5)Me(4)tBu, C(5)Me(4)SiMe(2)tBu and C(5)Me(4)SiMe(3), respectively, have been prepared by the reaction of ZnCl(2) with the appropriate Cp'-transfer reagent. For a comparative structural study, the known [Zn(C(5)H(4)SiMe(3))(2)] (1), has also been investigated, along with the mixed-ring zincocenes [Zn(C(5)Me(5))(C(5)Me(4)SiMe(3))] (6) and [Zn(C(5)Me(5))(C(5)H(4)SiMe(3))] (7), the last two obtained by conproportionation of [Zn(C(5)Me(5))(2)] with 5 or 1, as appropriate. All new compounds were characterised by NMR spectroscopy, and by X-ray methods, with the exception of 7, which yields a side-product (C) upon attempted crystallisation. Compounds 5 and 6 were also investigated by (13)C CPMAS NMR spectroscopy. Zincocenes 1 and 2 have infinite chain structures with bridging Cp' ligands, while 3 and 4 exhibit slipped-sandwich geometries. Compounds 5 and 6 have rigid, eta(5)/eta(1)(sigma) structures, in which the monohapto C(5)Me(4)SiMe(3) ligand is bound to zinc through the silyl-bearing carbon atom, forming a Zn--C bond of comparable strength to the Zn--Me bond in ZnMe(2). Zincocene 5 has dynamic behaviour in solution, but a rigid eta(5)/eta(1)(sigma) structure in the solid state, as revealed by (13)C CPMAS NMR studies, whereas for 6 the different nature of the Cp' ligands and of the ring substituents of the eta(1)-Cp' group (Me and SiMe(3)) have permitted observation for the first time of the rigid eta(5)/eta(1) solution structure. Iminoacyl compounds of composition [Zn(eta(5)-C(5)Me(4)R)(eta(1)-C(NXyl)C(5)Me(4)R)] resulting from the reactions of some of the above zincocenes and CNXyl (Xyl=2,6-dimethylphenylisocyanide) have also been obtained and characterised.

Chemical investigations of Prionosciadium thapsoides roots led to the isolation of the new dihydrofurochromones (S)-(+)-4'-O-angeloyl-5-O-methylvisamminol (1) and (S)-(+)-4'-O-senecioyl-5-O-methylvisamminol (2), together with the known coumarins jatamansin, buchtormin, isopteryxin, isosamidin, psoralen, and bergapten. The structures of 1 and 2 were determined by 1D and 2D NMR experiments, and their absolute configuration was established by chemical correlation with (+)-5-O-methylvisamminol (3), whose structure was secured by single-crystal X-ray diffraction analysis and its absolute configuration was established as S by vibrational circular dichroism spectroscopy in comparison to DFT B3LYP/DGDZVP calculations.

Diastereomerically pure cationic Rh(I) complexes derived from phosphinite thioglycosides I were used as catalysts in highly enantioselective hydrogenations of enamides. The conformational similarity of alpha-D-arabinopyranose with beta-L-galactopyranose allows the synthesis of both enantiomers of alpha-amino acid derivatives such as D- and L-DOPA in excellent ee (97% and 98%), using derivatives of the former sugar as catalyst precursors.

The absolute configurations (AC) of natural occurring 6-hydroxyeuryopsin (1), of its acetyl derivative 2, and of eremophilanolide 8 were confirmed by comparison of the experimental vibrational circular dichroism (VCD) spectra with theoretical curves generated from density functional theory (DFT) calculations. Initial analyses were carried out using a Monte Carlo searching with the MMFF94 molecular mechanics force field. All MMFF94 conformers were further optimized using DFT at the B3LYP/6-31G(d) level of theory, followed by calculations of their vibrational frequencies at the B3LYP/6-31G(d,p); the VCD spectra of 2 and 8 were also calculated at the B3PW91/DGDZVP level of theory. Good agreement between theoretical and experimental VCD curves unambiguously verified the 4S,5R,6S absolute configuration for 1 and 2, and the 1S,4S,5R,6S,8S,10S configuration for 8.

The sesquiterpene p-benzoquinone perezone (1), isolated from Perezia adnata var. alamani (Asteraceae), and its non-natural derivatives isoperezone (2), dihydroperezone (3), dihydroisoperezone (4), and anilidoperezone (5) were tested as antifeedants against the herbivorous insects Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. Compounds 1-5 exhibited strong antifeedant activity against L. decemlineata and M. persicae, and elicited a low response by S. littoralis. Antifeedant activity on L. decemlineata and M. persicae increased when the hydroxyl group at C-3 in perezone (1) was changed to C-6 to give isoperezone (2). The same effect was found with hydrogenation of the double bond of the alkyl chain of (1) to yield dihydroperezone (3). In contrast, hydrogenation of this double bond in isoperezone (2) to give dihydroisoperezone (4) led to a reduction in antifeedant activity. Determination of the phytotoxic activity of 1-5 revealed that 3 had a significant inhibition effect on Lactuca sativa radicle length growth.

Medical training curricula is a constantly evolving field. The objective of the present study is to analyze the changes the field has undergone. Our sources of information include demographic and health surveys, surveys carried out with students and faculty members and medical school guidelines from prestigious teaching centers. We compared medical curricula offered in Mexico as well as international trends. We analyzed context requirements, current status and future trends in biological, sociomedical and clinical disciplines; research and teaching methods; adequate academic programs. We describe the state of affairs in medical teaching in Mexico and the challenges that academic programs are currently facing. We propose a curricula with horizontal and vertical planning according to skills and competences that focus on health problems to foster scientific reasoning. Teaching strategies that are student-focused and foster significant/long-lasting learning. We suggest the need to include early clinical activities, communication skills and training in technological resources. Finally, there is a need to define a teaching profile that is consistent with training programs, to include experts in technology and modern teaching methods in order to establish permanent monitoring mechanisms, and to offer incentives to academics and administrative personnel.

Concise and efficient strategies toward the synthesis of D2h- and D3h-symmetric cyclodextrin analogues alternating alpha,alpha'-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs) are reported. The conformational properties of these cyclooligosaccharides are governed by the rigidity of the alpha,alpha'-trehalose disaccharide repeating unit and the partial double-bond character of the N-(C=X) linkages. In contrast to the typical concave-shaped cavity of cyclodextrins (CDs), CTs feature a convex-shaped hydrophobic cavity in which the beta-face of the monosaccharide subunits is oriented toward the inner side, as supported by NMR and modeling (molecular mechanics and dynamics) studies. In the case of cyclodimeric CTs (CT2s), the existence of intramolecular hydrogen bonds results in collapsed cavities, too small to allow the formation of inclusion complexes with organic molecules. Cyclotrimeric CTs (CT3s) display cavity sizes that are intermediate between those of alphaCD and betaCD, ideally suited for the complexation of complementary guests with ternary symmetry such as adamantane 1-carboxylate (AC). The higher flexibility of the pseudoamide bridges as compared with classical glycosidic linkages endow these glyconanocavities with some conformational adaptability properties, making them better suited than CDs for complexation of angular guests, as seen from comparative inclusion capability experiments against the fluorescent probes 6-p-toluidinonaphthalene-2-sulfonate (TNS; linear) and 8-anilinonaphthalene-1-sulfonate (ANS; angular).

In order to discover molecular biomarkers in radiation response we investigated the effects of X-radiation on radioresistant K562 cells by using a comparative proteomic analysis. In treated cells 29 up-regulated and 10 down-regulated proteins were detected by image analysis and identified by mass spectrometry. Elongation factor 1 alpha 1 and stress-70 protein showed a 6.2 and 5.4 fold increase respectively in treated cells. Additional proteins such us pi and omega classes glutathione transferases, ATP synthase D chain, were also found to be up-regulated, suggesting that the enzyme belonging to the cellular detoxification system against oxidative stress and energetic metabolism may have a key role in the cellular response to radiation injury. This data set may provide a useful tool to design a combined chemo- and radiotherapic strategy against leukemia disease.

CD38 is a type II transmembrane glycoprotein found mainly on the plasma membrane involved in the metabolism of cADPR and NAADP, two nucleotides with calcium mobilizing activity independent of inositol trisphosphate. Recent data report the presence of CD38 in different cellular compartments raising new questions about its effective role in cellular metabolism. In rat hepatocyte nuclei, CD38 has been proposed as a responsive to cADPR integral inner membrane protein suggesting that the nuclear envelope may also be an important source of Ca2+ stores. Further reports indicating that CD38 is localized in nuclear compartments in a variety of cell types and tissues including brain, liver, eye, spleen, and bone raise the condition of resolving the question concerning the effective presence of CD38 within the nucleus. Here we report data supporting the presence of CD38 at nuclear level independently of expression of surface CD38. We utilized two different human leukemia cell lines expressing or not expressing CD38 molecule on their cell surface. The morphological and biochemical results including enzymatic activity and proteomic determinations explain the effective nuclear localization of CD38 in human Raji and K562 cells. Since cell nucleus is a complex and highly dynamic environment with many functionally specialized regions, the nuclear localization of specific proteins represents an important mechanism in signal transduction. The presence of CD38 at the interchromatin region whether linked to nuclear scaffold or stored in nuclear structures as micronuclei and Cajal bodies co-localizing with coilin, suggests its involvement in nuclear processes including transcription, replication, repairing and splicing.

The insect antifeedant and toxic activity of hydroxyperezone (1), its derivatives 2-9, along with 3-hydroxy- (10) and 6-hydroxythymoquinone (11) were studied against Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. The antifeedant tests showed that L. decemlineata was the most sensitive insect, followed by M. persicae, while S. littoralis was not deterred by compounds 1-11. Leucohydroxyperezone tetraacetate (3), oxoperezinone (6), dihydroleucoperezinone diacetate (7), 3-hydroxy- (10) and 6-hydroxythymoquinone (11) showed strong activity against L. decemlineata. 1 and 7 exhibited moderate deterrent activity against M. persicae, while 1 and dihydroleucohydroxyperezone tetraacetate (4) acted as post-ingestive antifeedants to S. littoralis. The phytotoxic activity of compounds 1-11 was also evaluated. Hydroxyperezone (1) strongly inhibited seed germination at 24 h, while the activity of 3-8 and 10 was moderate. The level of radicle growth inhibition obtained with compounds 1-5 and 8-11 was significant (< 50%).