NMR and EPR study of the interaction of tris(3-hydroxy-4-pyridinonato) Ga(III) complexes with liposomes that mimic plant membranes.

We performed an NMR and EPR study of the interaction of four [Ga(3,4-HPO)] chelates with liposomes derived from a soybean extract (SEL) and simpler formulations using POPC (100%) and POPE:POPC (50%). Parent [Fe(3,4-HPO)] chelates are eligible to prevent Iron Deficiency Chlorosis and we took advantage of the likenesses of the ions Fe (III) and Ga (III), and the fact their metal ion complexes are isostructural, to perform a combined NMR and EPR study to get information about the permeation properties of the complexes. The results demonstrate the presence of liposomes loaded with Ga-chelates and that the distribution of complexes alongside the bilayer is dependent on their structure.

Mesenchymal Stem/ Stromal Cells metabolomic and bioactive factors profiles: A comparative analysis on the umbilical cord and dental pulp derived Stem/ Stromal Cells secretome.

Mesenchymal Stem/ Stromal Cells assume a supporting role to the intrinsic mechanisms of tissue regeneration, a feature mostly assigned to the contents of their secretome. A comparative study on the metabolomic and bioactive molecules/factors content of the secretome of Mesenchymal Stem/ Stromal Cells derived from two expanding sources: the umbilical cord stroma and the dental pulp is presented and discussed. The metabolic profile (Nuclear Magnetic Resonance Spectroscopy) evidenced some differences in the metabolite dynamics through the conditioning period, particularly on the glucose metabolism.

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids from Pilocarpus microphyllus Leaves.

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds.

Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products.

Mesenchymal stem cells are posing as a promising character in the most recent therapeutic strategies and, since their discovery, extensive knowledge on their features and functions has been gained. In recent years, innovative sources have been disclosed in alternative to the bone marrow, conveying their associated ethical concerns and ease of harvest, such as the umbilical cord tissue and the dental pulp. These are also amenable of cryopreservation and thawing for desired purposes, in benefit of the donor itself or other patients in pressing need.

Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach.

In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs).

Relevant interactions of antimicrobial iron chelators and membrane models revealed by nuclear magnetic resonance and molecular dynamics simulations.

The dynamics and interaction of 3-hydroxy-4-pyridinone fluorescent iron chelators, exhibiting antimicrobial properties, with biological membranes were evaluated through NMR and molecular dynamics simulations. Both NMR and MD simulation results support a strong interaction of the chelators with the lipid bilayers that seems to be strengthened for the rhodamine containing compounds, in particular for compounds that include ethyl groups and a thiourea link. For the latter type of compounds the interaction reaches the hydrophobic core of the lipid bilayer.

MSCs conditioned media and umbilical cord blood plasma metabolomics and composition.

Human mesenchymal stem cells (hMSCs) from umbilical cord (UC) blood (UCB) and matrix are tested clinically for a variety of pathologies but in vitro expansion using culture media containing fetal bovine serum (FBS) is essential to achieve appropriate cell numbers for clinical use. Human UCB plasma (hUCBP) can be used as a supplement for hMSCs culture, since UCB is rich in soluble growth factors and due to worldwide increased number of cryopreserved UCB units in public and private banks, without the disadvantages listed for FBS. On the other hand, the culture media enriched in growth factors produced by these hMSCs in expansion (Conditioned medium--CM) can be an alternative to hMSCs application.

Structural characterization of inclusion complexes between cyanidin-3-O-glucoside and β-cyclodextrin.

Inclusion complex formation between the multiple equilibrium forms of cyanidin-3-O-glucoside (cy3glc) and β-cyclodextrin (β-CD) was investigated using a combined approach of NMR spectroscopy and Molecular Dynamics simulation. Diffusion ordered NMR spectroscopy (DOSY) and study of nuclear Overhauser effects (NOE) were used to determine the selective intermolecular interactions and structure of these complexes in aqueous solution. The observed chemical shift displacements of resonance signals of protons from the interior of β-CD cavity and protons belonging to the hemiketal (B) and cis-chalcone forms (Cc), the diffusion measurements using DOSY and the NOE studies have anticipated the formation of an inclusion complex between these two forms and β-CD.

NMR study of the supramolecular structure of dual drug-loaded poly(butylcyanoacrylate) nanoparticles.

Nuclear magnetic resonance (NMR) spectroscopy has been used for structural characterization of 5-fluorouracil (5FU) & daunorubicin (DAU) co-loaded poly(butylcyanoacrylate) nanoparticles (PBCN), prepared by an anionic polymerization of n-butylcyanoacrylate, probing two different drug loading approaches. Diffusion ordered spectroscopy, obtained through pulsed field gradient NMR experiments, has been performed to determine the overall structure of the 5FU & DAU co-loaded PBCN and to clarify the mechanisms of drug immobilization and location in the polymer matrix of PBCN. Physicochemical properties such as composition, size, surface chemistry and shape have been defined.

Chitosan conjugates for DNA delivery.

Graft copolymers of chitosan and maltodextrin were synthesized by reductive amination of a low molecular weight chitosan. The degree of substitution is 70% or above, as quantified by nuclear magnetic resonance spectroscopy, at molar ratios of chitosan glucosamine units and maltodextrin of 1 : 1 and 1 : 5. The high substitution degree generates a water-soluble compound at pH 7.

Rhodamine labeling of 3-hydroxy-4-pyridinone iron chelators is an important contribution to target Mycobacterium avium infection.

We have recently demonstrated that tripodal hexadentate chelators, based on 3-hydroxy-4-pyridinone units, can limit the access of iron to bacteria and have a significant inhibitory effect in the intramacrophagic growth of Mycobacterium avium. The results showed that the chelation of iron is a determinant although not sufficient property for antimicrobial activity. The rhodamine B isothiocyanate labelled chelator (MRH7) exhibited the strongest inhibitory activity and was identified as a lead compound since a dose response effect was observed.

Interaction of 5-fluorouracil loaded nanoparticles with 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes used as a cellular membrane model.

Nuclear magnetic resonance (NMR) spectroscopy and steady-state fluorescence anisotropy were used to study the behavior and interaction of 5-fluorouracil, both in a free form (5FU) and included in the polymer matrix of poly(butylcyanoacrylate) nanoparticles (5FUPBCN) with a phospholipid bilayer of large unilammellar vesicles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), as a model system of biomembranes. The results confirm an interaction and penetration of 5FU into the phospholipid bilayer of DMPC liposomes. Different mechanisms of drug transfer from the aqueous environment into the model membrane environment, for the free drug and that incorporated into polymer nanoparticles, are suggested: (i) concentration-dependent reversible diffusion of the free 5FU and (ii) sustained 5FU release from nanoparticles adsorbed on the liposome surface resulting in continuous delivery of the drug into the phospholipid bilayers of the DMPC liposomes.

Chemical characterization and physical and biological activities of rhamnolipids produced by Pseudomonas aeruginosa BN10.

Pseudomonas aeruginosa BN10 isolated from hydrocarbon-polluted soil was found to produce rhamnolipids when cultivated on 2% glycerol, glucose, n-hexadecane, and n-alkanes. The rhamnolipids were partially purified on silica gel columns and their chemical structures elucidated by combination of one- and two-dimensional 1H and 13C NMR techniques and ESI-MS analysis. Eight structural rhamnolipid homologues were identified: Rha-C10-C8, Rha-C10-C10, Rha-C10-C12:1, Rha-C10-C12, Rha2-C10-C8, Rha2-C10-C10, Rha2-C10-C12:1, and Rha2-C10-C12.

NMR insight into the supramolecular structure of daunorubicin loaded polymer nanoparticles.

Nuclear magnetic resonance (NMR) spectroscopy has been employed for structural characterization of daunorubicin-loaded poly(butylcyanoacrylate) nanoparticles. Measurements of the nuclear relaxation times (T(1)) and application of diffusion ordered spectroscopy (DOSY), obtained through pulsed field gradient (PFG) NMR experiments, have been performed to determine the supramolecular structure of the drug-polymer conjugates and to clarify the mechanisms of drug immobilization in the polymer matrix. The results confirm the coexistence of three different interaction mechanisms between the drug daunorubicin and the poly(butylcyanoacrylate) nanoparticles, viz.

Tautomeric equilibria of 5-fluorouracil anionic species in water.

It has long been postulated that rare tautomeric or ionized forms of nucleic acid bases may play a role in mispair formation. Therefore, ab initio quantum chemical investigations on the tautomeric equilibrium in 5-fluorouracil (5FU) and its anions (deprotonated from N1, AN1, and from N3, AN3) and their tautomeric forms in water were performed. The effect of the water as solvent was introduced using solute-solvent clusters (four water molecules).

Synthesis and characterization of new galanthamine derivatives comprising peptide moiety.

New analogues of galanthamine containing peptide fragments either at 6 or 11 position, were synthesized by reaction between galanthamine molecule and dipeptides and tripeptide, derivatives of N-(3,4-dichlorophenyl)-D,L-Ala-OH. The best results according to yields, easily purification of the target products, and simplicity of the scheme realisation was achieved by using of cyanomethyl ester of Boc-Gly-OH as activated compound.

Physicochemical characterization and in vitro behavior of daunorubicin-loaded poly(butylcyanoacrylate) nanoparticles.

The design, preparation and characterization of poly(butylcyanoacrylate) nanoparticles as a drug-delivery system for daunorubicin is reported. A range of light scattering [photon correlation spectroscopy (PCS)], spectroscopic [(1)H nuclear magnetic resonance ((1)H NMR), Fourier transform infrared (FTIR), chromatographic [gel permeation chromatography (GPC)] and quantum chemical techniques have been employed for the physicochemical characterization of drug-loaded nanoparticles and to clarify the mechanisms of drug immobilization in the polymer matrix. The presence of daunorubicin in the polymerization medium was found to affect both the degree of polymerization and the compactness of the resulting nanoparticles.

Theoretical and spectroscopic study of 2-substituted indan-1,3-diones: a coherent picture of the tautomeric equilibrium.

The structures of some 2-substituted indan-1,3-diones are investigated in the gas phase and solution using quantum chemical calculations and spectral (NMR, IR, and UV) measurements. The influence of the substituent at the 2-position on the tautomeric equilibrium of 2-substituted indan-1,3-diones in solvents with different polarity is evaluated. It is shown that the equilibrium in 2-formyl-indan-1,3-dione and 2-acetyl-indan-1,3-dione is shifted to the 2-hydroxyalkylidene-indan-1,3-dione tautomer, while 2-carboxyamide-indan-1,3-dione exists as a mixture of two tautomers, 2-(hydroxyaminomethylidene)-indan-1,3-dione and 2-carboamide-1-hydroxy-3-oxo-indan, with extremely fast proton transfer between them.

Selective sensors for Zn2+ cations based on new green fluorescent poly(amidoamine) dendrimers peripherally modified with 1,8-naphthalimides.

The paper reports on the spectral photophysical characteristics of two new fluorescent PAMAM dendrimers of zero and second generation decoreted with 1,8-naphthalimide units, designed for ionic detection. The dendrimers were studied by (1)H NMR, (13)C NMR, FT-IR spectroscopy and elemental analysis. Their ability to detect ions has been evaluated in acetonitrile by monitoring the quenching of the fluoresence intensity.

Synthesis of cinnamoyl and hydroxycinnamoyl amino acid conjugates and evaluation of their antioxidant activity.

Fifteen amides of cinnamic, ferulic and sinapic acids with natural and unnatural C-protected amino acids have been synthesized. The amides (E)-N-(feruloyl)-L-tyrosine methyl ester (10), (E)-N-(feruloyl)-L-phenylalanine t-butyl ester (11), (E)-N-(sinapoyl)-L-tyrosine methyl ester (13) and (E)-N-(sinapoyl)-L-phenylalanine t-butyl ester (15) with a free carboxyl group of amino acids have been found in nature. The rest of the compounds are unknown.

Poly(amidoamine) dendrimer peripherally modified with 4-N,N-dimethylaminoethyleneamino-1,8-naphthalimide as a sensor of metal cations and protons.

A new poly(amidoamine) dendrimer from second generation whose periphery comprises sixteen fluorescent 4-N,N-dimethylaminoethylamino-1,8-naphthalimide units has been synthesized and characterized. In DMF, the dendrimer shows sensitivity to the presence of Cu(2+), Fe(3+) and protons. The changes in the fluorescence intensity of the material are in opposite directions if acids or metals are present.