The stoichiometry and apparent stability constants (β) of the complexes formed between Ni2+ and four different hydroxyflavones (3-hydroxyflavone, 5-hydroxyflavone, chrysin, and galangin) were ...determined in methanolic solutions. A multivariate curve resolution methodology was applied to estimate the β values using UV–vis spectroscopic data. All the complexes exhibit 1:2 metal:ligand stoichiometry. The highest and lowest β values were obtained for the galangin and 5-hydroxyflavone complexes, respectively. The formation of the complexes was confirmed by Fourier transform infrared spectroscopy. Time-dependent density functional theory and natural transition orbital analysis were performed to describe the spectroscopic features of the studied compounds, and quantum theory of atoms in molecules was applied to evaluate different intermolecular interactions. Good correlations were obtained between the calculated UV–vis absorption spectra using the M06 functional and the experimental ones. The main absorption band of these Ni2+ complexes have an important metal-to-ligand charge transfer mixed with an intraligand charge transfer (ILCT). Two possible chelation sites were considered for the interaction of Ni2+ with galangin. The combination of spectroscopic and quantum chemistry calculations results indicate the existence of an equilibrium between the two carbonyl-hydroxyl sites of galangin in the Ni2+ complex formation.
The solvatochromic characteristics of flavone and 7-hydroxyflavone were investigated in neat and binary solvent mixtures. The spectral shifts of these solutes were correlated with the Kamlet and Taft ...parameters (α, β and π*) using linear solvation energy relationships. The multiparametric analysis indicates that both specific hydrogen bond donor ability and non-specific dipolar interactions of the solvents play an important role in absorption maxima of flavone in pure solvents. The hydrogen bond acceptor ability of the solvent was the main parameter affecting the absorption maxima of 7-hydroxyflavone. The simulated absorption spectra using a TD-DFT method were in good agreement with the experimental ones for both flavones. Index of preferential solvation was calculated as a function of solvent composition. Preferential solvation by ethanol was detected in cyclohexane-ethanol and acetonitrile-ethanol mixtures for flavone and in acetonitrile-ethanol mixtures for 7-hydroxyflavone. These results indicate that intermolecular hydrogen bonds between solute and solvent are responsible for the non-linear variation of the solvatochromic shifts on the mole fraction of ethanol in the analyzed binary mixtures.
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•Niclosamide (NSD) forms a 1:2 aqueous complex with 2-hydrxypropyl-β-cyclodextrin.•Complexed NSD is oxidized through a Riboflavin-photosensitized process.•The photodecomposition ...process is much more efficient than in homogeneous medium.•Photodegradation is affected by dynamic and electrostatic factors and pH changes.
A kinetic and mechanistic study of the daylight-mediated photooxidation of the multifunctional drug Niclosamide (NSD) was carried out in aqueous solutions. NSD is a frequent contaminant suspended in natural waters. The aqueous dissolution of the practically insoluble NSD was driven by the presence of 2-hydrxypropyl-β-cyclodextrin (HPβCD). The already proposed formation of an inclusion complex between NSD-HPβCD was confirmed through theoretical studies. NSD-nanoencapsulation within the oligosaccharide occurs with a 1:2 stoichiometry, being the drug embedded into a cavity of two HPβCD molecules, in a so called head-to-head orientation.
The Reactive Oxygen Species singlet molecular oxygen, superoxide radical anion and hydrogen peroxide, generated through the visible-light absorber sensitizers Riboflavin and Rose Bengal, are effectively intercepted by the encapsulated biocide and contribute to its photodegradation. The overall NSD photooxidation rate, determined through oxygen consumption indicates that the process is relatively highly efficient in the microheterogeneous aqueous media as compared to NSD in MeOH solution, and to phenol (PHE) in pure water. The paradigmatic water-contaminant PHE was taken a as reference in order to evaluate the persistence of the NSD under photosensitized irradiation in aqueous medium. The photooxidation mechanism of NSD is affected by cyclodextrin complexation, due to dynamic limitations, electrostatic interactions and pH changes upon NSD dissolution in aqueous HPβCD. In this sense, the NSD-HPβCD complex can be seen as a sort of nanoreactor that enables the photodegradation of the biocide in water, under daylight conditions.
Hydroxycinnamic acid content and ferulic acid dehydrodimer content were determined in 11 barley varieties after alkaline hydrolysis. Ferulic acid (FA) was the most abundant hydroxycinnamate with ...concentrations ranging from 359 to 624 μg/g dry weight. p-Coumaric acid (PCA) levels ranged from 79 to 260 μg/g dry weight, and caffeic acid was present at concentrations of <19 μg/g dry weight. Among the ferulic acid dehydrodimers that were identified, 8-O-4‘-diFA was the most abundant (73−118 μg/g dry weight), followed by 5,5‘-diFA (26−47 μg/g dry weight), the 8,5‘-diFA benzofuran form (22−45 μg/g dry weight), and the 8,5‘-diFA open form (10−23 μg/g dry weight). Significant variations (p < 0.05) among the different barley varieties were observed for all the compounds that were quantified. Barley grains were mechanically fractionated into three fractions: F1, fraction consisting mainly of the husk and outer layers; F2, intermediate fraction; and F3, fraction consisting mainly of the endosperm. Fraction F1 contained the highest concentration for ferulic acid (from 77.7 to 82.3% of the total amount in barley grain), p-coumaric acid (from 78.0 to 86.3%), and ferulic acid dehydrodimers (from 79.2 to 86.8%). Lower contents were found in fraction F2, whereas fraction F3 exhibited the lowest percentages (from 1.2 to 1.9% for ferulic acid, from 0.9 to 1.7% for p-coumaric acid, and <0.02% for ferulic acid dehydrodimers). The solid barley residue from the brewing process (brewer's spent grain) was ∼5-fold richer in ferulic acid, p-coumaric acid, and ferulic acid dehydrodimers than barley grains. Keywords: Barley; brewer's spent grain; ferulic acid; p-coumaric acid; ferulic acid dehydrodimers
Pluripotent stem cells possess the capacity for self‐renewal and the ability to differentiate into all cell types of the three embryonic germ layers. Accordingly, given their potential use in ...regenerative medicine, they have long attracted the attention of researchers. Embryonic stem cells (ESCs) represent the model pluripotent stem cell population. However, the use of ESCs in regenerative therapies faces major hurdles—namely, immune rejection and the necessity to use early‐stage embryos for ESC isolation.
Clinical Pharmacology & Therapeutics (2011) 89 5, 746–749. doi:10.1038/clpt.2010.341
The complexation of methyl salicylate (MS) and ethyl salicylate (ES), non-steroidal analgesic, anti-inflammatory and antirrheumatic drugs with beta-cyclodextrin (betaCD) has been studied from ...thermodynamic and structural points of view. The complexation with betaCD has been investigated using reversed-phase liquid chromatography. Retention behavior has been analyzed on a reverse-phase column Luna 18(2) 5 microm. The mobile-phase was methanol:water in different ratios (55:45 to 70:30) in which betaCD (1-9 mM) was incorporated as a mobile-phase additive. The decrease in retention times with increasing concentrations of betaCD enables the determination of the apparent stability constant of the complexes. Values at 30 degrees C with 55% methanol were K(MS:betaCD): 15.84 M(-1) and K(ES:betaCD): 12.73 M(-1) for MS and ES, respectively. The apparent stability constants decrease as the polarity of the solvent decreases. The low solubility of MS and ES in aqueous solution has been improved by complexation with betaCD (1-9 mM). The stability constants of the complexes obtained from the phase-solubility diagrams using a UV-vis spectrophotometric method were K(MS:betaCD): 229 M(-1) and K(ES:betaCD): 166 M(-1). In addition, semi-empirical quantum mechanics calculations using AM1 and PM3 methods in vacuum were performed. The energetically favorable inclusion structures were identified and the most favorable orientation for the inclusion process was found to be the head-down orientation for both complexes. Enthalpy for encapsulation processes was found to be favorable (DeltaH degrees <0), while entropy (DeltaS degrees <0) and Gibbs free energy were unfavorable (DeltaG degrees >0). By means of HPLC and UV-vis measurements and quantum mechanics calculations, it was found that MS and ES form a 1:1 inclusion complex with betaCD. The theoretical results are in agreement with the experimental parameters associated with the encapsulation process.
Summary
We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the ...clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4–5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life‐sustaining measures were withdrawn in 413/553 of non‐donors (75%).
Scope
The aim of this work was to investigate the effects of high‐intensity ultrasound (sonication), on the structure and allergenicity of the major cow's milk allergen, beta‐lactoglobulin (BLG).
...Methods and results
Structural changes upon sonication of BLG were monitored by circular dichroism spectroscopy, tryptophan emission fluorescence, hydrophobic dye and retinol binding, as well as digestibility and phenol‐oxidase cross‐linking capacity. Allergenicity was monitored in individual patients’ sera, basophil activation test, and skin prick testing in 41 cow's milk allergy patients. Uncontrolled local temperature changes induced modifications in BLG secondary structure accompanied by formation of dimers, trimers, and oligomers of BLG that were more digestible by pepsin and had reduced retinol binding. Controlled temperature conditions induced changes in secondary structure of BLG without causing formation of oligomers, or changing protein's capacity to bind retinol. Both sonicated forms of BLG had more exposed hydrophobic surfaces than native BLG and underwent facilitated cross‐linking reaction with phenol‐oxidase. Sonication had a minor effect on IgE‐binding properties of BLG.
Conclusion
Sonication‐induced structural changes in major whey allergen were not clinically significant in cow's milk allergy patients. Ultrasound can be a safe procedure for dairy processing as it maintains the nutritional value and does not increase allergenic potential of BLG.
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