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Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results : The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m 2 vs. 55.8 mL/min/1.73 m 2 , p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found ( F (1,70) = 5.15, p = 0.026), with an R 2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions : some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Gene therapy is one of the most potential therapeutic approaches in direct and specific regulation of biological functions of macrophages at the gene level for efficient cell therapy. However, the delivery of genetic material to macrophages is extremely challenging, because of low stability, specificity and inability of therapeutic genes to efficiently enter the cells. Here, we present a method that uses the hybrid electrospun architectures based on gelatin-alginate decorated with carboxylated graphene oxide (HAG/G) as efficient substrate for loading and in vitro local and controlled delivery of plasmid DNA (pDNA) to macrophages as an alternative to systemic gene delivery carriers. Polyethyleneimine (PEI) is employed to assemble PEI/pDNA nanoparticles (Np) - used as model of carrier. The dispersion of GO-COOH sheets shifts the surface zeta potential of HAG/G to high negative value (SZP = -16.8 ± 2.21 mV) and further increases the encapsulation efficiency of PEI/pDNA Np onto hybrid HAG/G electrospun architectures to ∼ 69 % (HAG/G-Np). The in vitro biological investigations show a good metabolic activity of macrophages seeded onto HAG/G-Np (MTT assay), while gene expression experiments (fluorescent microscopy) show a 30 % increase in transient gene transfection of cells cultured in the presence of HAG/G-Np as compared to those incubated with free PEI/pDNA Np., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Strigolactones (SLs) have potential to be used in sustainable agriculture to mitigate various stresses that plants have to deal with. The natural SLs, as well as the synthetic analogs, are difficult to obtain in sufficient amounts for practical applications. At the same time, fluorescent SLs would be useful for the mechanistic understanding of their effects based on bio-imaging or spectroscopic techniques. In this study, new fluorescent SL mimics containing a substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive furan-2-one moiety were prepared. The structural, spectroscopic, and biological activity of the new SL mimics on phytopathogens were investigated and compared with previously synthetized fluorescent SL mimics. The chemical group at the C-6 position of the naphthalimide ring influences the fluorescence parameters. All SL mimics showed effects similar to GR24 on phytopathogens, indicating their suitability for practical applications. The pattern of the biological activity depended on the fungal species, SL mimic and concentration, and hyphal order. This dependence is probably related to the specificity of each fungal receptor-SL mimic interaction, which will have to be analyzed in-depth. Based on the biological properties and spectroscopic particularities, one SL mimic could be a good candidate for microscopic and spectroscopic investigations.

Although both localized nuclear magnetic resonance spectroscopy (MRS) and non-localized nuclear magnetic resonance spectroscopy (NMR) generate the same information, i.e., spectra generated by various groups from the structure of metabolites, they are rarely employed in the same study or by the same research group. As our review reveals, these techniques have never been applied in the same study of methylmalonic acidemia (MMA), propionic acidemia (PA) or vitamin B 12 deficiency patients. On the other hand, MRS and NMR provide complementary information which is very valuable in the assessment of the severity of disease and efficiency of its treatment. Thus, MRS provides intracellular metabolic information from localized regions of the brain, while NMR provides extracellular metabolic information from biological fluids like urine, blood or cerebrospinal fluid. This paper presents an up-to-date review of the NMR and MRS studies reported to date for methylmalonic and propionic acidemias. Vitamin B 12 deficiency, although in most of its cases not inherited, shares similarities in its metabolic effects with MMA and it is also covered in this review.

Solid activators based on waste glass for the manufacture of one-part alkali-activated fly ash/red mud materials were synthesized, characterized, and tested in this work. The synthesis was carried out via alkaline fusion with sodium hydroxide at different reaction temperatures and at different sodium hydroxide/waste glass mass ratios. The results showed that the reaction temperature decisively influences the properties of the obtained solid activators. Thus, the best results regarding the water solubility of solid activators were obtained for the synthesis temperature of 600 °C, regardless of the sodium hydroxide/waste glass mass ratio. Also, the use of these assortments of solid activators led to obtaining the best compressive strength of one-part alkali-activated fly ash/red mud materials. The best results were obtained for the solid activator synthesized at a temperature of 600 °C and a sodium hydroxide/glass waste mass ratio of two.

The poor water solubility of natural antioxidants restricts their bioavailability and therapeutic use. We aimed to develop a new phytosome formulation with active compounds from extracts of ginger (GINex) and rosehips (ROSAex) designed to increase their bioavailability, antioxidant and anti-inflammatory properties. The phytosomes (PHYTOGINROSA-PGR) were prepared from freeze-dried GINex, ROSAex and phosphatidylcholine (PC) in different mass ratios using the thin-layer hydration method. PGR was characterized for structure, size, zeta potential, and encapsulation efficiency. Results showed that PGR comprises several different populations of particles, their size increasing with ROSAex concentration, having a zeta potential of ~-21mV. The encapsulation efficiency of 6-gingerol and β-carotene was >80%. 31 P NMR spectra showed that the shielding effect of the phosphorus atom in PC is proportional to the amount of ROSAex in PGR. PGR with a mass ratio GINex:ROSAex:PC-0.5:0.5:1 had the most effective antioxidant and anti-inflammatory effects in cultured human enterocytes. PGR-0.5:0.5:1 bioavailability and biodistribution were assessed in C57Bl/6J mice, and their antioxidant and anti-inflammatory effects were evaluated after administration by gavage to C57Bl/6J mice prior to LPS-induced systemic inflammation. Compared to extracts, PGR induced a 2.6-fold increase in 6-gingerol levels in plasma and over 40% in the liver and kidneys, in parallel with a 65% decrease in the stomach. PGR treatment of mice with systemic inflammation increased the sera antioxidant enzymes paraoxonase-1 and superoxide dismutase-2 and decreased the proinflammatory TNFα and IL-1β levels in the liver and small intestine. No toxicity was induced by PGR either in vitro or in vivo. In conclusion, the phytosome formulation of GINex and ROSAex we developed resulted in stable complexes for oral administration with increased bioavailability, antioxidant and anti-inflammatory potential of their active compounds.

Due to its inherent properties and wide availability, cellulose acetate is an extremely competitive candidate for the production of polymeric membranes. However, for best results in particular applications, membrane modification is required in order to minimize unwanted interactions and introduce novel characteristics to the pristine polymer. In this study, the surface of commercial cellulose acetate membranes was functionalized with 4'-aminobenzo-15-crown-5 ether, using a covalent bonding approach. The main goal was the improvement of the membranes biomineralization ability, thus making them prospective materials for bone regeneration applications. The proposed reaction mechanism was confirmed by XPS and NMR analysis while the presence of the functionalization agents in the membranes structure was showed by ATR FT-IR and Raman spectra. The effects of the functionalization process on the morphology, thermal and mechanical properties of the membranes were studied by SEM, TGA and tensile tests. The obtained results revealed that the cellulose acetate membranes were successfully functionalized with crown ether and provided a good understanding of the interactions that took place between the polymer and the functionalization agents. Moreover, promising results were obtained during the Taguchi biomineralization studies. SEM images, EDX mapping and XRD spectra indicating that the CA-AB15C5 membranes have a superior Ca 2+ ions retention ability, this causing an accentuated calcium phosphate deposition on the modified polymeric fibers, compared to the neat CA membrane., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Exposure to per- and polyfluoroalkyl substances (PFASs) is associated with increased blood cholesterol. Although elevated cholesterol is a well-established risk factor for cardiovascular diseases (CVD), it is not clear whether PFASs affect this risk. Lipoprotein subclasses are emerging biomarkers for disease risk and lipoprotein profiling may provide an insight to physiological implications of PFAS exposure. We explored the association between serum PFAS concentrations and lipoprotein subclasses in a cross-sectional study. We determined the concentrations and lipid composition of the major subclasses of lipoproteins in plasma samples from 127 adult participants of the EuroMix human biomonitoring study by nuclear magnetic resonance (NMR). Serum concentrations of 17 PFASs showed a detection frequency between 30 and 100% and were included in further analyses. We examined the associations between PFAS concentrations and lipoprotein subclasses by linear mixed-effect regression models, adjusted for confounders. In the adjusted models, positive associations were found between several PFASs and cholesterol concentrations in large to medium sized HDL and medium sized LDL particles. We found a 4-12% increase in HDL cholesterol per interquartile range (IQR) increase for several PFASs. In women the associations with PFNA, PFUnDA, PFDoDA and PFOS were significant after adjustment for multiple comparisons. Similar magnitude of change was observed between longer chained PFASs and LDL cholesterol, and a few of these associations reached significance for cholesterol in large to medium LDL particle sizes in women. No significant associations with plasma triglycerides were observed. However, most PFASs tended to be associated with reduction in VLDL (very low-density lipoproteins) particle number and VLDL triglyceride. Findings from this exploratory study, suggest that background PFAS exposures influence particle size distributions and lipid composition of plasma lipoprotein subclasses, and that these effects may be more prominent in women. A two-points lipoprofiling for all subjects indicated both low intra-individual variability and good analytical reproducibility., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Most patients presenting in an emergency unit with acute coronary syndromes (ACS) (which include non-ST-elevation myocardial infarction (NSTEMI), ST-elevation MI (STEMI), and unstable angina) usually meet at least two cardiovascular risk factors, such as dyslipidemia, arterial hypertension, diabetes mellitus type 2, obesity, history of or current smoking, etc. Most ACS patients suffer from a type of dyslipidemia, and in addition to this there are ACS patients rushed into the emergency units for which the feeding status is unknown. Thus, we set out to evaluate the effect of fasting on 16 blood metabolite concentrations and 114 lipoprotein parameters on one control group and a group of statin-treated ACS patients hospitalized in a cardiovascular emergency unit, using Nuclear Magnetic Resonance (NMR) spectroscopy. The results indicated trends (in terms of number of cases, but not necessarily in terms of the magnitude of the effect) for as many as four metabolites and 48 lipoproteins. The effect was defined as a trend for results showing over 70% of the cases from either one or both groups that experienced parameter changes in the same direction (i.e., either increased or decreased). In terms of magnitude, the effect is rather low, leading to the overall conclusion that in cardiovascular (CV) emergency units, the blood samples analyzed in any feeding status would provide close results and very valuable information regarding prognosis and for fast decisions on patient's proper management.

The saponification value of fats and oils is one of the most common quality indices, reflecting the mean molecular weight of the constituting triacylglycerols. Proton nuclear magnetic resonance ( 1 H-NMR) spectra of fats and oils display specific resonances for the protons from the structural patterns of the triacylglycerols (i.e., the glycerol backbone), methylene (-CH 2 -) groups, double bonds (-CH=CH-) and the terminal methyl (-CH 3 ) group from the three fatty acyl chains. Consequently, chemometric equations based on the integral values of the 1 H-NMR resonances allow for the calculation of the mean molecular weight of triacylglycerol species, leading to the determination of the number of moles of triacylglycerol species per 1 g of fat and eventually to the calculation of the saponification value (SV), expressed as mg KOH/g of fat. The algorithm was verified on a series of binary mixtures of tributyrin (TB) and vegetable oils (i.e., soybean and rapeseed oils) in various ratios, ensuring a wide range of SV. Compared to the conventional technique for SV determination (ISO 3657:2013) based on titration, the obtained 1 H-NMR-based saponification values differed by a mean percent deviation of 3%, suggesting the new method is a convenient and rapid alternate approach. Moreover, compared to other reported methods of determining the SV from spectroscopic data, this method is not based on regression equations and, consequently, does not require calibration from a database, as the SV is computed directly and independently from the 1 H-NMR spectrum of a given oil/fat sample.

Novel fluorescent strigolactone derivatives that contain the piperidine-substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive 3-methyl-furan-2-one unit were synthesized and their spectroscopic properties investigated. The solvatochromic behavior of these piperidine-naphthalimides was monitored in solvents of different polarity using the electronic absorption and fluorescence spectra. These compounds exhibited a strong positive solvatochromism taking into account the change of solvent polarity, and the response mechanism was analyzed by fluorescence lifetime measurements. According to Catalan and [f(n), f(ε), β, α] solvent scales, the dipolarity and polarizability are relevant to describe the solute-solvent interactions. The emission chemosensing activity was discussed in order to determine the water content in organic environments. The emission intensity of these compounds decreased rapidly in dioxane, increasing water level up to 10%. Measuring of quantum yield indicated that the highest values of quantum efficiency were obtained in nonpolar solvents, while in polar solvents these derivatives revealed the lowest quantum yield. The fluorescence decay can be described by a monoexponential model for low water levels, and for higher water contents a biexponential model was valid.

Nuclear magnetic resonance (NMR) metabolomics is currently popular enough to attract both specialized and non-specialized NMR groups involving both analytical trained personnel and newcomers, including undergraduate students. Recent interlaboratory studies performed by established NMR metabolomics groups demonstrated high reproducibility of the state-of-the-art NMR equipment and SOPs. There is, however, no assessment of NMR reproducibility when mixing both analytical experts and newcomers. An interlaboratory assessment of NMR quantitation reproducibility was performed using two NMR instruments belonging to different laboratories and involving several operators with different backgrounds and metabolomics expertise for the purpose of assessing the limiting factors for data reproducibility in a multipurpose NMR environment. The variability induced by the operator, automatic pipettes, NMR tubes and NMR instruments was evaluated in order to assess the limiting factors for quantitation reproducibility. The results estimated the expected reproducibility data in a real-life multipurpose NMR laboratory to a maximum 4% variability, demonstrating that the current NMR equipment and SOPs may compensate some of the operator-induced variability.

The paper reports on monitoring methylmalonic aciduria (MMA)-specific and non-specific metabolites via NMR urinomics. Five patients have been monitored over periods of time; things involved were diet, medication and occasional episodes of failing to comply with prescribed diets. An extended dataset of targeted metabolites is presented, and correlations with the type of MMA are underlined. A survey of previous NMR studies on MMA is also presented.

The influence of waste glass and red mud addition as alternative source of aluminosilicate precursors on the microstructural, mechanical, and leaching properties of bottom ash-based geopolymer was studied in this work through mineralogical, morphological, and spectroscopic analysis, as well as by conducting compressive strength and leaching tests. The bottom ash-based geopolymer composites were synthesized by adding a constant amount of waste glass (10% by weight) and increasing amounts of red mud (up to 30% by weight). The results derived from FTIR, 29 Si and 27 Al MAS NMR, and SEM-EDX revealed that adding up to 10% (by weight) red mud to the synthesis mixes leads to an increase in the degree of geopolymerization of the activated mixes. The compressive strength followed the same trend. An increase of more than 10% (by weight) red mud added to the synthesis mixes results in a significant decrease of compressive strength of the geopolymer composites. A low leachability of geopolymer composites in regard with their contaminants was revealed especially for those with good compressive strength.

Two chitosan extracts were prepared by chemical and enzymatic treatment of Ganoderma lucidum mushroom, as an alternative source to crustacean shells. The molecular weight of the enzymatic extract was lower than that of the chemical one and of shrimp chitosan, as determined by viscosity measurements. Characteristic signals were identified in the 1 H-NMR spectra and high deacetylation degree indicated good physico-chemical properties for both mushroom chitosan extracts. The scavenging capacity of mushroom chitosan extracts was moderate against the synthetic radicals of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), but higher values were observed for the enzymatic extract, compared to the chemical extract and shrimp chitosan. In vitro cytotoxicity was evaluated in L929 mouse fibroblast cell lines and the results of MTT assay showed good cytocompatibility in the tested range of concentrations. The growth of Gram-positive bacteria was inhibited more than Gram-negative bacteria in the presence of mushroom chitosan extracts, in particular by the chemical one, indicating their efficiency as antimicrobial agents. All these results strengthen the evidence of mushroom polysaccharide preparations availability for biomedical applications., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) involved in galactose metabolism. Bacterial infections are a known cause of early morbidity and mortality in children with classic galactosemia. The most common agent is Escherichia c (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia.oli , but in rare situations, other bacteria are incriminated. We report a case of a three-week-old female patient with galactosemia, who presented with Group B S treptococcus (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia., Competing Interests: The authors declare no conflict of interest.

Water uptake in vesicles and the subsequent exchange between water protons and amide -NH protons in amino acids can be followed by a new, highly sensitive, type of magnetic resonance spectroscopy: dynamic nuclear polarisation (DNP)-enhanced NMR in the liquid state. Water hydrogen atoms are detected prior to and after their transfer to molecular sites in peptides and proteins featuring highly-accessible proton-exchangeable groups, as is the case for the -NH groups of intrinsically disordered proteins. The detected rates for amide proton-water proton exchange can be modulated by membrane-crossing rates, when a membrane channel is interposed. We hyperpolarised water proton spins via dynamic nuclear polarisation followed by sample dissolution (d-DNP) and transferred the created polarisation to -NH groups with high solvent accessibility in an intrinsically disordered protein domain. This domain is the membrane anchor of c-Src kinase, whose activity controls cell proliferation. The hindrance of effective water proton transfer rate constants observed in free solvent when a membrane-crossing step is involved is discussed. This study aims to assess the feasibility of recently-introduced hyperpolarised (DNP-enhanced) NMR to assess water membrane crossing dynamics.

Stable Schiff bases containing a furoxan moiety are synthesized as single regioisomers by the reaction of 3-methyl-2-oxy-furazan-4-carbaldehydewith various amino compounds at room temperature. The structures of synthesized compounds were fully characterized by multinuclear NMR spectroscopy and X-ray crystallography. The effect of synthesized Schiff bases containing a furoxan moiety on biological generation of reactive oxygen species and nitric oxide in plant tissues was investigated for the first time by fluorescence microscopy and the released NO identified as nitrite with Griess reagent. There is a good correlation between the biological generation of NO determined by fluorescence microscopy and with Griess reagent. Some of the synthesized compounds exhibited both nitric oxide and reactive oxygen species generation abilities and represent potential NO donors in plant tissues., Competing Interests: The authors declare no competing interests. The affiliation of some coauthors to commercial companies [EG FG LV MCV] does not alter our adherence to PLOS ONE policies on sharing data and materials.

The importance of strigolactones in plant biology prompted us to synthesize simplified strigolactone mimics effective as exogenous signals for rhizosphere organisms. New strigolactone mimics easily derived from simple and available starting materials in significant amounts were prepared and fully characterized. These compounds contain an aromatic or heterocyclic ring, usually present in various bioactive molecules, connected by an ether link to a furan-2-one moiety. The new synthesized strigolactone mimics were confirmed to be active on plant pathogenic fungi and parasitic weed seeds., Competing Interests: The authors declare no conflict of interest.

Several 3,5-disubstituted isoxazoles were obtained in good yields by regiospecific 1,3-dipolar cycloaddition reactions between aromatic nitrile oxides, generated in situ from the corresponding hydroxyimidoyl chlorides, with non-symmetrical activated alkynes in the presence of catalytic amounts of copper(I) iodide. Effects of 3,5-disubstituted isoxazoles on nitric oxide and reactive oxygen species generation in Arabidopsis tissues was studied using specific diaminofluoresceine dyes as fluorescence indicators.

The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported.

The one-pot three-component reactions of 1-substituted benzimidazoles with ethyl bromoacetate and electron-deficient alkynes, in 1,2-epoxybutane, gave a variety of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. The influence of experimental conditions on the course of reaction was investigated. A novel synthetic pathway starting from benzimidazoles unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three-component reaction.

The paper describes a new pathway for an efficient synthesis of natural and bioactive drimanic compounds ( - )-pereniporin B (1) and ( - )-cinnamosmolide (2) from ketodiol 7, an intermediate obtained before from accessible labdane diterpenoid (+)-larixol (3). The key step involves allylic bromination of acetate 8 with N-bromosuccinimide. The in vitro antimicrobial and antifungal activities of all compounds are also reported. Their structures were confirmed by both spectroscopic data and chemical transformations.

The availability of data for reference values in cerebrospinal fluid for healthy humans is limited due to obvious practical and ethical issues. The variability of reported values for metabolites in human cerebrospinal fluid is quite large. Dogs present great similarities with humans, including in cases of central nervous system pathologies. The paper presents the first study on healthy dog cerebrospinal fluid metabolomic profile using (1)H NMR spectroscopy. A number of 13 metabolites have been identified and quantified from cerebrospinal fluid collected from a group of 10 mix breed healthy dogs. The biological variability as resulting from the relative standard deviation of the physiological concentrations of the identified metabolites had a mean of 18.20% (range between 9.3% and 44.8%). The reported concentrations for metabolites may be used as normal reference values. The homogeneity of the obtained results and the low biologic variability show that the (1)H NMR analysis of the dog's cerebrospinal fluid is reliable in designing and interpreting clinical and therapeutic trials in dogs with central nervous system pathologies.

Reaction between ortho-phthalaldehyde and various aroylhydrazines unexpectedly yields N-(1-(2-aryl-hydrazono)isoindolin-2-yl)benzamides as major products along with the predictable 1,2-bis-aroylhydrazones. NMR investigation of the major reaction products indicate the presence of a mixture of geometrical isomers, in various ratios. Single crystal X-ray diffraction confirms the proposed structure and indicates a Z configuration of the C═N double bond substitutents. Optimization of the condensation reaction conditions enabled quantitative isolation of the cyclic isomer. Oxidation of the isomers with bis(trifluoroacetoxy)iodobenzene (PIFA) leads to rapid formation of new highly fluorescent 1,2-bis(5-aryl-1,3,4-oxadiazol-2-yl)benzenes.

A novel synthesis of natural drimanic compounds, (-)-albrassitriol (2) and (-)-6-epi-albrassitriol (3), has been carried out starting from an easily available labdane diterpenoid, (+)-larixol (1). In a two-step procedure, (+)-larixol (1) was converted into 14,15-bisnorlab-7-ene-6,13-dione (9), which was then submitted to a Norrish type II photochemical degradation yielding drim-7,9(11)-diene-6-one (10), whose treatment with OsO4 led selectively to the formation of drim-7-ene-9α,11-diol-6-one (12). The same compound was obtained by selective epoxidation of the C(9)-C(11) double bond in drim-7,9(11)-diene-6-one (10) with monoperphtalic acid. Treatment of the resulting mixture of α- and β-epoxides (13 and 14) with HClO4 yielded drim-7-ene-9α,11-diol-6-one (12). Reduction of the C6-carbonyl group in drim-7-ene-9α,11-diol-6-one (12) with LiAlH4 afforded (-)-albrassitriol (2) and (-)-6-epi-albrassitriol (3), 12.4% and 13.6% overall yields, respectively.

A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with β-cyclodextrin (β-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with β-CD has been studied by NMR, ESI-MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds ((1)J(HC)3=207 Hz, (1)J(CH)5=214 Hz, for PCZ; (1)J(HC)3=208 Hz and (1)J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI-MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of β-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the β-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents.

The 1H and 13C NMR chemical shifts of 1,2,3,4,5,6,7,8-octahydroacridine, 12 of its 9-substituted derivatives, and of the corresponding N-oxides were determined, assigned, and discussed in terms of 9-substituent effects and effects of N-oxidation. A good linear correlation was found between the 13C chemical shifts of the aromatic carbons in octahydroacridines and those of respective carbons in the corresponding N-oxides., (Copyright 2009 John Wiley & Sons, Ltd.)

A new, efficient and general method for preparation of N-substituted-pyridazinones using ultrasound irradiation is reported. Under ultrasound the reaction time decreases substantially, the yields are high and the reaction conditions are mild. It was noticed that substituents at the 3-(6)-position of pyridazone heterocycle have a substantial influence on the reactivity, while the effect of the substituents at the 1-(2)-position seems to be of minor importance. A comparative study of the reactions performed under ultrasound conditions versus at room temperature has been done.

The (15)N NMR chemical shifts of 1,2,3,4,5,6,7,8-octahydroacridine, 12 of its 9-substituted derivatives, and of the corresponding N-oxides were measured and examined in terms of the 9-substituent effects and the effects of N-oxidation. For the 9-substituent effects, good linear correlations were found with the Taft and Swain-Lupton substituent constants, for both octahydroacridines and their N-oxides. The (15)N chemical shifts of both octahydroacridines and their N-oxides also correlate well, linearly with the (13)C chemical shifts of the para-carbons in analogously substituted benzene derivatives.Within the studied compounds, the magnitudes of the N-oxidation effects range from - 16.4 to - 27.4 ppm (shielding), and also correlate linearly with the Taft and Swain-Lupton substituent constants, as well as with the bond orders of the N(+)-O(-) bonds in the corresponding N-oxides. Furthermore, a very good linear correlation is found between the (15)N chemical shifts of octahydroacridines and those of the corresponding N-oxides. From the (15)N chemical shifts data, the Taft and Swain-Lupton substituent constants for the diacetylamino group (-NAc(2)) were evaluated in the present paper, as follows: sigma(R) = 0.07 and sigma(I) = 0.15; R = 0.08 and F= 0.20., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Cleavage of the Se-Se bond in [2-{O(CH(2)CH(2))(2)NCH(2)}C(6)H(4)](2)Se(2) (1) and [2-{MeN(CH(2)CH(2))(2)NCH(2)}C(6)H(4)](2)Se(2) (2) by treatment with SO(2)Cl(2), bromine or iodine (1 : 1 molar ratio) yielded [2-{O(CH(2)CH(2))(2)NCH(2)}C(6)H(4)]SeX [X = Cl (3), Br (4), I (5)] and [2-{MeN(CH(2)CH(2))(2)NCH(2)}C(6)H(4)]SeI (6). The compounds were characterized in solution by NMR spectroscopy (1H, 13C, 15N, 77Se, 2D experiments). The solid-state molecular structures of 1-3, 4.HBr, 5 and 6 were established by single crystal X-ray diffraction. In all cases T-shaped coordination geometries, i.e. (C,N)SeSe (1, 2), (C,N)SeX (3, 5, 6; X = halogen) or CSeBr(2) (4.HBr), were found. Supramolecular associations in crystals based on hydrogen contacts are discussed.

The (15)N chemical shifts of 13 N-methylpiperidine-derived mono-, bi- and tricycloaliphatic tertiary amines, their methiodides and their N-epimeric pairs of N-oxides were measured, and the contributions of specific structural parameters to the chemical shifts were determined by multilinear regression analysis. Within the examined compounds, the effects of N-oxidation upon the (15)N chemical shifts of the amines vary from +56 ppm to +90 ppm (deshielding), of which approx. +67.7 ppm is due to the inductive effect of the incoming N(+)--O(-) oxygen atom, whereas the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The effects of quaternization vary from -3.1 ppm to +29.3 ppm, of which approx. +8.9 ppm is due to the inductive effect of the incoming N(+)--CH(3) methyl group, and the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The shift effects of the C-alkyl substituents in the amines, the N-oxides and the methiodides are discussed., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Unlabelled: Biochemical analysis of synovial fluid is important in orientating the diagnosis of joint effusions. Its composition reflects the metabolic status of synovial tissue correlated with different rheumatic pathologies. The aim of this study was to compare the information provided by usual biochemical tests and proton magnetic resonance spectroscopy (MRS) analysis of synovial fluid, in order to detect potential characteristics of joint effusion correlated to the pathogenesis of arthritis., Patients and Methods: This study included 99 synovial fluid samples obtained from patients with different etiology of arthritis--rheumatoid arthritis (RA), osteoarthritis (OA), gout, seronegative spondylarthropathies and septic arthritis, which underwent routine laboratory tests available in the Department of Rheumatology, Cantacuzino Clinical Hospital, Bucharest. Patients were admitted in the hospital between January 2003 and June 2005. Synovial samples were examined in parallel using MRS determination. Spectra have been recorded on a Bruker Avance DRX 400 MHz spectrometer., Results: We obtained a good correlation between biochemical analysis and MRS determination. RA samples have offered the most important information regarding the complex composition of pathological synovial fluid. In addition to the markedly elevated lactate (p < 0.009) and diminished glucose concentration (p < 0.02) in RA samples vs. OA, MRS analysis provides evidence for reduced mean chain length of very-low-density-lipoprotein (VLDL)-associated triacylglycerols (p < 0.05), high levels of ketone bodies (p < 0.05), ceramide (p < 0.02) and citrulline (p < 0.04). OA samples have shown a characteristically increased level of N-glucosamine (p < 0.04) and creatine (p < 0.04). For the other pathologies, there are no characteristic markers detected, except for the extremely increased level of lactate and the decreased concentration of glucose in septic arthritis., Conclusions: This study gave us the possibility to provide a complex exploration of the biochemical environment of synovial fluid using the MRS method, that offers us the opportunity to understand more about the pathogenesis of rheumatic diseases, to provide information regarding the degree of inflammation, immune infiltration and apoptosis in RA, cartilage degradation and muscular secondary atrophy in OA. The most valuable information is focused on the possibility to have a simultaneous detection of more than 26 different metabolites in synovial fluid samples.