Chemical constituents of açai berry pulp (Euterpe oleracea Mart.) by LC-UV-BPSU/NMR and LC-UV-SPE/NMR.

The techniques LC-UV-BPSU and LC-UV-SPE/NMR were applied for the first time in the analysis of açai berry (Euterpe oleracea Mart.) pulp extracts. Those techniques allowed the identification of twenty-three metabolites: Valine (1), citric acid (2), tachioside (3), isotachioside (4), α-guaiacylglycerol (5), syringylglycerol (6), uridine (7), adenosine (8), dimethoxy-1,4-benzoquinone (9), koaburaside (10), protocatechuic acid (11), eurycorymboside B (12), 7',8'-dihydroxy-dihydrodehydroconiferyl alcohol-9-O-ß-D-glucopyranoside (13), orientin (14), homoorientin (15), dihydrokaempferol-3-glucoside (16), isolariciresinol-9'-O-ß-D-glucopyranoside (17), 5'-methoxyisolariciresinol-9'-O-ß-D-glucopyranoside (18), cyanidin-3-O-glucoside (19), cyandin-3-O-rutenoside (20), 9,12-octadecadienoic acid (Z,Z)-2-hydroxy-1-(hydroxymethyl) ethyl ester (21), linolenic acid (22), and 1,2-di-O-α-linolenoyl-3-O-ß-D-galactopyranosyl-sn-glycerol (23). In this plant, compounds 3, 4, 5, 6, 8, 10, 12, 17, 18, 21, and 23 are reported for the first time. All the structures were determined through extensive analyses of 1D and 2D NMR data, mass spectrometry, and comparison with published data. This methodology has proven to be an efficient alternative to the analysis of complex extracts containing a large variety of compounds.

Modulation of the Excited States of Ruthenium(II)-perylene Dyad to Access Near-IR Luminescence, Long-Lived Perylene Triplet State and Singlet Oxygen Photosensitization.

Herein, we present a novel ruthenium(II)-perylene dyad (RuPDI-Py) that combines the photophysical properties of pyrrolidine-substituted perylene diimide (PDI-Py) and the ruthenium(II) polypyridine complex [Ru(phen)3]2+. A comprehensive study of excited-state dynamics was carried out using time-resolved and steady-state methods in a dimethyl sulfoxide solution. The RuPDI-Py dyad demonstrated excitation wavelength-dependent photophysical behavior. Upon photoexcitation above 600 nm, the dyad exclusively exhibits the near-infrared (NIR) fluorescence of the 1PDI-Py state at 785 nm (τfl = 1.50 ns). In contrast, upon photoexcitation between 350 and 450 nm, the dyad also exhibits a photoinduced electron transfer from the {[Ru(phen)3]2+} moiety to PDI-Py, generating the charge-separated intermediate state {Ru(III)-(PDI-Py)•-} (4 µs). This state subsequently decays to the long-lived triplet excited state 3PDI-Py (36 µs), which is able to sensitize singlet oxygen (1O2). Overall, tuning 1O2 photoactivation or NIR fluorescence makes RuPDI-Py a promising candidate for using absorbed light energy to perform the desired functions in theranostic applications.

Antioxidant activity of an Mg(II) compound containing ferulic acid as a chelator: potential application for active packaging and riboflavin stabilisation.

Foods rich in riboflavin (Rf) are susceptible to degradation due to oxidative processes with the formation of radicals. Herein, we describe the features and stability of an Mg(II) complex containing ferulic acid (fer) and 1,10-phenanthroline (phen) as chelators: henceforth called Mg(phen)(fer). The electrochemical behavior of Mg(phen)(fer) is pH dependent and results from the stabilisation of the corresponding phenoxyl radical via complexation with Mg(II). This stabilisation enhances the antioxidant activity of Mg(phen)(fer) with respect to free fer and commercial antioxidants. Mg(phen)(fer) scavenges and neutralizes DPPH˙ (IC50 = 15.6 µmol L-1), ABTS˙+ (IC50 = 5.65 µmol L-1), peroxyl radical (IC50 = 5.64 µg L-1) and 1O2 (IC50 = 0.7 µg m-1). Mg(phen)(fer) effectively protects riboflavin (Rf) against photodegradation by quenching the singlet excited states of Rf regardless of the conditions. Also, the complex Mg(phen)(fer) was effectively incorporated into starch films, broadening its applications, as shown by microbiological studies. Thus, Mg(phen)(fer) has high potential for use in Rf-rich foods and to become a new alternative to the synthetic antioxidants currently used.

Phomactinine, the First Nitrogen-Bearing Phomactin, Produced by Biatriospora sp. CBMAI 1333.

Metabolomics analyses and improvement of growth conditions were applied toward diversification of phomactin terpenoids by the fungus Biatriospora sp. CBMAI 1333. Visualization of molecular networking results on Gephi assisted the observation of phomactin diversification and guided the isolation of new phomactin variants by applying a modified version of chemometrics based on a fractional factorial design. Consequentially, the first nitrogen-bearing phomactin, phomactinine (1), with a new rearranged carbon skeleton, was isolated and identified. The strategy combining metabolomics and chemometrics can be extended to include bioassay potency, structure novelty, and metabolic diversification connected or not to genomic analyses.

Identification and characterization of a recombinant cysteine peptidase (AsCathL) from leaf-cutting ant Atta sexdens Linnaeus, 1758 (Hymenoptera, Formicidae).

Cysteine peptidases are involved in physiological processes of insect development and have been considered as potential targets for the development of insect control strategies. In this study, we obtained a recombinant cysteine cathepsin L (AsCathL) from leaf-cutting ant (Atta sexdens), a species from the order Hymenoptera who causes enormous damage to crops, natural forests and reforested areas. RT-qPCR showed AsCathL expression throughout insect development and in all body parts of the adult insect analysed, suggesting its role as a lysosomal cathepsin. AsCathL encodes a protein of 320 amino acid residues consisting of a pro-peptide and the mature with amino acids sequence over 67% similarity with lysosomal cathepsin L of species from Lepidoptera and Diptera. Phylogenetic tree revealed that AsCathL is very similar to predicted cathepsins found in other ants. Recombinant AsCathL was expressed in insoluble form by Escherichia coli Arctic Express (DE3) RIL, purified under denaturing conditions and refolded. The enzyme showed hydrolytic activity in vitro towards synthetic substrate Z-Phe-Arg-AMC at acidic pH. Synthetic inhibitor E-64 acted against peptidase activity and a study regarding the interaction between E-64 and AsCathL using nuclear magnetic resonance (NMR) revealed that 83.18% from all E-64 molecules are irreversibly bound to AsCathL. In addition, the proteolytic activity of AsCathL was strongly inhibited by recombinant sugarcane cystatins with Ki ranging from 0.6 nM to 2.95 nM. To the best of our knowledge this is the first report characterizing a cysteine peptidase from leaf-cutting ants, which may contribute to future studies of ants' cathepsins.

Preparation, Characterization and Study of the Dissociation of Naproxen from Its Chitosan Salt.

Salts of naproxen (NAP) with chitosan (CTS) and reticulated chitosan (CEP) were prepared under optimized conditions to maximize the yield of reaction. The objective was to evaluate the dissociation in water, which can guide studies of release of the drug from biopolymeric salts in pharmaceutical applications. Higher salification was found after 24 h of reaction at 60 °C in a molar ratio 1:1.05 (CTS:NAP, mol/mol), resulting in a degree of substitution (DS) of 17% according to 13C NMR, after neutralization of the -NH2 group of the biopolymer by the carboxylic group of the drug. The presence of NAP salt is evidenced by FTIR bands related to the -NH3+ group at 856 cm-1, a decrease in crystallinity index in XRD diffractograms as well as changes in mass loss ratios (TG/DTG/DTA) and increased thermal stability of the salt regarding CTS itself. The CEPN crosslinked salt presented a DS = 3.6%, probably due to the shielding of the -NH2 groups. Dissociation studies revealed that at pH 2.00, dissociation occurred faster when compared to at pH 7.00 in the non-reticulated salt, while the opposite was observed for the reticulated one.

Probing the acetylcholinesterase inhibitory activity of a novel Ru(II) polypyridyl complex and the supramolecular interaction by (STD)-NMR.

Currently, acetylcholinesterase (AChE) inhibitors are the only anti-Alzheimer drugs commercially available. Despite their wide use those drugs are all dose dependent and their effect last for no longer than two years, with several side effects. The search of novel acetylcholinesterase (AChE) inhibitors remains as the main scientific route. Here we describe the synthesis, characterization, biological activity and an NMR binding-target study of a novel cis-[Ru(Bpy)2(EtPy)2]2+, (RuEtPy), Bpy = 2,2'-bipyridine and EtPy = 4,2-Ethylamino-pyridine) as a potential AChE inhibitor. The classic Ellman's colorimetric assay suggests that the RuEtPy exhibits a high inhibitory activity, following a competitive mechanism, with a remarkable low inhibition constant (Ki ≈ 16.8 µM), together with a IC50 = 39 µM. Hence, we have studied the spatial interactions for this novel candidate towards the human acetylcholinesterase (hAChE) using saturation transfer difference (STD)-NMR, in order to describe the mechanism of the interaction. NMR binding-target results shows that the 4,2-Ethylamino-Pyridine group is spatially closer to hAChE surface chemical arrangement than 2,2' bipyridine counterpart, exerting an efficient intermolecular interaction, with a low dissociation constant (KD ≈ 55 µM), probing that 4,2-Ethylamino-pyridine motif plays a key role in the inhibitory action.

Probing the Structural Dynamics of the Coil-Globule Transition of Thermosensitive Nanocomposite Hydrogels.

Nanocomposite hydrogels have emerged to exhibit multipurpose properties, boosting especially the biomaterial field. However, the development and characterization of these materials can be a challenge, especially stimuli-sensitive materials with dynamic properties in response to external stimuli. By employing UV-vis spectroscopy and NMR relaxation techniques, we could outline the formation and behavior of thermosensitive nanocomposites obtained by in situ polymerization of poly(N-vinylcaprolactam) (PNVCL) and mesoporous silica nanofibers under temperature stimuli. For instance, inorganic nanoparticles covalently linked to PNVCL changed the pattern of temperature-induced phase transition despite showing similar critical temperatures to neat PNVCL. Thermodynamic parameters indicated the formation of an interconnected system of silica and polymer chains with reduced enthalpic contribution and mobility. The investigation of water molecule and polymer segment motions also revealed that the absorption and release of water happened in a wider temperature range for the nanocomposites, and the polymer segments respond in different ways during the phase transition in the presence of silica. This set of techniques was essential to reveal the polymer motions and structural features in nanocomposite hydrogels under temperature stimuli, demonstrating its potential use as experimental guideline to study multicomponent nanocomposites with diverse functionalities and dynamic properties.

Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311.

Three antifungal macrolides cyphomycin (1), caniferolide C (2) and GT-35 (3) were isolated from Streptomyces sp. ISID311, a bacterial symbiont associated with Cyphomyrmex fungus-growing ants. The planar structures of these compounds were established by 1 and 2D NMR data and MS analysis. The relative configurations of 1-3 were established using Kishi's universal NMR database method, NOE/ROE analysis and coupling constants analysis assisted by comparisons with NMR data of related compounds. Detailed bioinformatic analysis of cyphomycin biosynthetic gene cluster confirmed the stereochemical assignments. Compounds 1-3 displayed high antagonism against different strains of Escovopsis sp., pathogen fungi specialized to the fungus-growing ant system. Compounds 1-3 also exhibited potent antiprotozoal activity against intracellular amastigotes of the human parasite Leishmania donovani with IC50 values of 2.32, 0.091 and 0.073 µM, respectively, with high selectivity indexes.

Functionalization of an Alginate-Based Material by Oxidation and Reductive Amination.

This research focused on the synthesis of a functional alginate-based material via chemical modification processes with two steps: oxidation and reductive amination. In previous alginate functionalization with a target molecule such as cysteine, the starting material was purified and characterized by UV-Vis, 1H-NMR and HSQC. Additionally, the application of FT-IR techniques during each step of alginate functionalization was very useful, since new bands and spiked signals around the pyranose ring (1200-1000 cm-1) and anomeric region (1000-750 cm-1) region were identified by a second derivative. Additionally, the presence of C1-H1 of ß-D-mannuronic acid residue as well as C1-H1 of α-L-guluronic acid residue was observed in the FT-IR spectra, including a band at 858 cm-1 with characteristics of the N-H moiety from cysteine. The possibility of attaching cysteine molecules to an alginate backbone by oxidation and post-reductive amination processes was confirmed through 13C-NMR in solid state; a new peak at 99.2 ppm was observed, owing to a hemiacetal group formed in oxidation alginate. Further, the peak at 31.2 ppm demonstrates the presence of carbon -CH2-SH in functionalized alginate-clear evidence that cysteine was successfully attached to the alginate backbone, with 185 µmol of thiol groups per gram polymer estimated in alginate-based material by UV-Visible. Finally, it was observed that guluronic acid residue of alginate are preferentially more affected than mannuronic acid residue in the functionalization.

Xanthation of alginate for heavy metal ions removal. Characterization of xanthate-modified alginates and its metal derivatives.

Xanthates are widely used in mining industry as collectors for its high affinity towards metal sulfides and precious metal ores. The possibility of using alginate for xanthation has not been explored yet despite the feasibility by the presence of hydroxyl groups alongside the polymeric chains. Therefore, this work aims to evaluate the alginate as a matrix for xanthation and its application on heavy metal ions removal. In order to obtain green materials, important pararmeter were explored such as the effect of reaction time (4-12 h), type of base (NaOH/KOH) and amount of carbon disulfide (2-10%v/v). Xanthated alginates were analyzed by NMR techniques and evidence of ß-elimination was detected at 5.45 ppm. Furthermore, the presence of S element was confirmed by EDS mapping technique, while XRD showed a semi-crystalline structure. On the other hand, the chemical shifts of δ(C=S) and ν(C=S) bands were found around 863-805 cm-1 and 662-602 cm-1 respectively. Also, a shoulder at 182 ppm is appreciated by NMR in solid state attributed to CS group. According to FESEM analyses, morphology of xanthated alginates is affected by interaction with heavy metal ions. Finally, suitable materials for the removal of heavy metal ions were established at optimum pH values.

A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains.

Many studies have linked the antimicrobial properties of kefir with the presence of bacteriocins and organic acids. In the present work, results obtained from bacteriostatic and bactericidal studies, and from RP-HPLC, Mass Spectrometry and proton NMR analysis, show that a sample of milk kefir grains is able to produce an antimicrobial fraction, denoted FK-1000, composed of sugars and amino acids, predominantly polymers of alanine, doublets of tyrosine and phenylalanine. Since this fraction is a lyophilized product whose molecular profile is different from bacteriocins and simple carboxylic acids, its antimicrobial effect cannot be attributed to these molecules, or to alcohols or hydrogen peroxide. The fraction is bactericidal against weak-acid-resistant MRSA and weak-acid resistant P. aeruginosa at pH 5, and is bacteriostatic against both pathogens at pH 7. In combination formulation, the FK-1000 fraction is able to increase fivefold the effect of streptomycin against P. aeruginosa and it is not toxic to human epithelial cells at antimicrobial concentrations. 16 S rRNA microbiota analysis of antimicrobial-producing and non-producing kefir grains demonstrated that they are distinct. In summary, the results indicate that milk kefir grains can produce different classes of molecules with potent antibiotic activity against resistant bacteria.

Polysaccharide-rich hydrogel formulation combined with photobiomodulation repairs UV-induced photodamage in mice skin.

Prolonged skin exposure to ultraviolet radiation (UVR) induces premature aging in both the epidermis and the dermis. Chronic exposure to UVR induces the activation of mitogen-activated protein kinase (MAPK) signaling pathway, activating c-Jun, c-Fos expression, and transcription factor of AP-1 activating protein. AP-1 activation results in the positive induction of matrix metalloproteinase (MMP) synthesis, which degrade skin collagen fibers. Polysaccharides from the fruit of Lycium barbarum (LBP fraction) have a range of activities and have been demonstrate to repair the photodamage. In different approaches, laser application aims to recover the aged skin without destroying the epidermis, promoting a modulation, called photobiomodulation (PBM), which leads to protein synthesis and cell proliferation, favoring tissue repair. Here we developed a topical hydrogel formulation from a polysaccharide-rich fraction of Lycium barbarum fruits (LBP). This formulation was associated with PBM (red laser) to evaluate whether the isolated and combined treatments would reduce the UVR-mediated photodamage in mice skin. Hairless mice were photoaged for 6 weeks and then treated singly or in combination with LBP and PBM. Histological, immunohistochemistry, and immunofluorescence analyses were used to investigate the levels of c-Fos, c-Jun, MMP-1, -2, and -9, collagen I, III, and FGF2. The combined regimen inhibited UVR-induced skin thickening, decreased the expression of c-Fos and c-Jun, as well as MMP-1, -2, and -9 and concomitantly increased the levels of collagen I, III, and FGF2. The PBM in combination with LBP treatment is a promising strategy for the repair of photodamaged skin, presenting potential clinical application in skin rejuvenation.

Synthesis, Characterization, and Low-Toxicity Study of a Magnesium(II) Complex Containing an Isovanillate Group.

The beneficial effect of polyphenols and magnesium(II) against oxidative stress motivated our research group to explore the antioxidant activity of phenMgIso, an aqueous soluble magnesium(II) complex containing 1,10-phenanthroline (phen) and isovanillic acid (Iso) as ligands. Combined electrospray ionization-mass spectrometry and DOSY-NMR techniques identified two complexes in methanolic solution: hexacoordinated [Mg(phen)2(Iso)]+ and tetracoordinated [Mg(phen)(Iso)]+. The cyclic voltammogram of phenMgIso in the anodic region showed a cyclic process that interrupts the isovanillic acid degradation, probably by stabilization of the corresponding phenoxyl radical via complexation with Mg(II), which is interesting for antioxidant applications. phenMgIso competes with 2,2,6,6-tetramethylpiperidine by 1O2 with IC50(1O2) = 15 µg m-1 and with nitrotetrazolium blue chloride by superoxide ions (IC50(O2 •-) = 3.6 µg mL-1). Exposure of both zebrafish (2 mg L-1) and wistar male rats (3 mg kg-1 day-1 dose for 21 days) to phenMgIso does not cause mortality or visual changes compared with the respective control groups, thus phenMgIso could be considered safe under the conditions of this study. Moreover, no significant changes in comparison to both control groups were observed in the biochemical parameters on the brain-acetylcholinesterase activity, digestive tract enzyme catalase, and glutathione-S-transferase. Conversely, the performance of superoxide dismutase activity in wistar male rats increased in the presence of a complex, resulting in enhanced capacity of rats for superoxide radical enzymatic scavenging. The synergistic action of phenMgIso may be explained by the strong electrostatic interaction between Mg(II) and the O,O(phenolate) group, which makes the Iso ligand easier to oxidize and deprotonate, generating a cyclic stable species under oxidative conditions.

Chronic Influence of Inspiratory Muscle Training at Different Intensities on the Serum Metabolome.

This study investigated the chronic effect of inspiratory muscle training (IMT) on the human serum metabolome in healthy male recreational cyclists. Using a randomized, parallel group design, twenty-eight participants were randomized to three IMT groups: low intensity (LI, n = 7); moderate intensity (MI, n = 10); and high intensity (HI, n = 11). The IMT was performed for 11 weeks. Another group of participants under the same conditions, who did not perform the IMT but participated in all procedures, was included as controls (CG, n = 6). Blood samples were collected one week before and after 11 weeks of IMT and analyzed for metabolite shifts using 1H NMR. Statistical analysis included a 4 (group) × 2 (time) repeated measures ANOVA using the general linear model (GLM), and multivariate principal component analysis (PCA). Untargeted metabolomics analysis of serum samples identified 22 metabolites, including amino acids, lipids, and tricarboxylic acid cycle intermediates. Metabolites shifts did not differ between groups, indicating that IMT at three intensity levels did not alter the serum metabolome relative to the control group. These results reveal novel insights into the metabolic effects of the IMT and are consistent with the results from other studies showing negligible chronic alterations in the serum metabolome in response to physical training.

A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains

Many studies have linked the antimicrobial properties of kefir with the presence of bacteriocins and organic acids. In the present work, results obtained from bacteriostatic and bactericidal studies, and from RP-HPLC, Mass Spectrometry and proton NMR analysis, show that a sample of milk kefir grains is able to produce an antimicrobial fraction, denoted FK-1000, composed of sugars and amino acids, predominantly polymers of alanine, doublets of tyrosine and phenylalanine. Since this fraction is a lyophilized product whose molecular profile is different from bacteriocins and simple carboxylic acids, its antimicrobial effect cannot be attributed to these molecules, or to alcohols or hydrogen peroxide. The fraction is bactericidal against weak-acid-resistant MRSA and weak-acid resistant P. aeruginosa at pH 5, and is bacteriostatic against both pathogens at pH 7. In combination formulation, the FK-1000 fraction is able to increase fivefold the effect of streptomycin against P. aeruginosa and it is not toxic to human epithelial cells at antimicrobial concentrations. 16 S rRNA microbiota analysis of antimicrobial-producing and non-producing kefir grains demonstrated that they are distinct. In summary, the results indicate that milk kefir grains can produce different classes of molecules with potent antibiotic activity against resistant bacteria.

A Supramolecular Interaction of a Ruthenium Complex With Calf-Thymus DNA: A Ligand Binding Approach by NMR Spectroscopy.

Lawsone itself exhibits interesting biological activities, and its complexation with a metal center can improve the potency. In this context a cytotoxic Ru-complex, [Ru(law)(dppb)(bipy)] (law = lawsone, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine), named as CBLAU, was prepared as reported. In this work, NMR binding-target studies were performed to bring to light the most accessible interaction sites of this Ru-complex toward Calf-Thymus DNA (CT-DNA, used as a model), in a similar approach used for other metallic complexes with anti-cancer activity, such as cisplatin and carboplatin. Advanced and robust NMR binding-target studies, among them Saturation Transfer Difference (STD)-NMR and longitudinal relaxometry (T1), were explored. The 1H and 31P -NMR data indicate that the structure of Ru-complex remains preserved in the presence of CT-DNA, and some linewidth broadening is also observed for all the signals, pointing out some interaction. Looking at the binding efficiency, the T1 values are highly influenced by the formation of the CBLAU-DNA adduct, decreasing from 11.4 s (without DNA) to 1.4 s (with DNA), where the difference is bigger for the lawsone protons. Besides, the STD-NMR titration experiments revealed a stronger interaction (KD = 5.9 mM) for CBLAU-DNA in comparison to non-complexed lawsone-DNA (KD = 34.0 mM). The epitope map, obtained by STD-NMR, shows that aromatic protons from the complexed lawsone exhibits higher saturation transfer, in comparison to other Ru-ligands (DPPB and bipy), suggesting the supramolecular contact with CT-DNA takes place by the lawsone face of the Ru-complex, possibly by a spatial π-π stacking involving π-bonds on nucleic acids segments of the DNA chain and the naphthoquinone group.

Study of the in vitro metabolic profile of a new α2-adrenergic agonist in rat and human liver microsomes by using liquid chromatography-multiple-stage mass spectrometry and nuclear magnetic resonance.

A potent synthetic α2-adrenergic agonist called PT-31, (3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione), was recently detected as a potential drug to be used as an adjuvant drug to treat chronic pain. The excellent pharmacological property of PT-31 highlights the importance in elucidating its metabolism, which could provide valuable information about its metabolite profile for further pharmacokinetics studies and additionally to estimate the impact of its metabolites on the efficacy, safety and elimination of PT-31. In this work, the study of the in vitro metabolism of PT-31 was initially carried out by using a liquid chromatography coupled to ion trap multiple-stage mass spectrometer (LC-IT-MSn) and a hybrid triple quadrupole/linear ion trap mass spectrometer (LC-QTrap). The production of at least three unknown oxidative metabolites was observed. Structural identification of the unknown metabolites was carried out by combination of LC-MS experiments, including selected reaction monitoring (SRM) and multi-stage full scan experiments. Further analysis of 1H-NMR led to the structural confirmation of the major metabolite. The results indicated that PT-31 was metabolized by a hydroxylation reaction in the imidazolidine-2,4-dione ring in rat and human liver microsomes, producing the metabolite 3-(2-chloro-6-fluorobenzyl)-5-hydroxyimidazolidine-2,4-dione in rat liver microsomes. A carbon hydroxylation onto the benzyl ring, produced two other minor metabolites of the PT-31 in rat liver microsomes.

The use of variable temperature 13 C solid-state MAS NMR and GIPAW DFT calculations to explore the dynamics of diethylcarbamazine citrate.

Experimental 13 C solid-state magic-angle spinning (MAS) Nuclear Magnetic Resonance (NMR) as well as Density-Functional Theory (DFT) gauge-including projector augmented wave (GIPAW) calculations were used to probe disorder and local mobility in diethylcarbamazine citrate, (DEC)+ (citrate)- . This compound has been used as the first option drug for the treatment of filariasis, a disease endemic in tropical countries and caused by adult worms of Wuchereria bancrofti, which is transmitted by mosquitoes. We firstly present 2D 13 C─1 H dipolar-coupling-mediated heteronuclear correlation spectra recorded at moderate spinning frequency, to explore the intermolecular interaction between DEC and citrate molecules. Secondly, we investigate the dynamic behavior of (DEC)+ (citrate)- by varying the temperature and correlating the experimental MAS NMR results with DFT GIPAW calculations that consider two (DEC)+ conformers (in a 70:30 ratio) for crystal structures determined at 293 and 235 K. Solid-state NMR provides insights on slow exchange dynamics revealing conformational changes involving particularly the DEC ethyl groups.

Chemical modification of alginate with cysteine and its application for the removal of Pb(II) from aqueous solutions.

It has been synthesized, characterized and tested a new biomaterial AlgS (sodium alginate functionalized with cysteine) to remove Pb(II) in aqueous media. The maximum Pb(II)-sorption capacity of AlgS (Qmax = 770 mg·g-1) is between almost two and nine times higher than other alginate-materials reported in the literature. Techniques, such as TGA/DSC, SEM/EDS, BET, FTIR, UV-Vis, XRD and 13C solid state-NMR have been used to study the chemical-modification of alginate at oxidation and aminofication stages. The formation of the imine intermediate (C=N), after 24 h of reaction was identified by a UV band at 348 nm. Typical IR-bands of AlgS were identified at 2970, 955, 949 and 1253 cm-1 which are associated to CH, SPb, SH and CN stretching vibrations, respectively. 13C solid state-NMR spectra of AlgS, show peaks at 33-38 ppm and 55-60 ppm associate to δ (HS-CH2-) of cysteine and δ (CN) respectively. The ΔH° and ΔG° negative values for Pb(II) sorption indicate that it is an exothermic process and occur spontaneously. Finally, it was found that the Pb(II) sorption on AlgS is significantly affected by the presence of cationic (Na+, Mg2+ and Al3+) and anionic (Cl-, NO3-) co-ions.