Studying molecular dynamics of the slow, structural, and secondary relaxation processes in series of substituted ibuprofens.

In this paper, the molecular dynamics of a series of ester derivatives of ibuprofen (IBU), in which the hydrogen atom from the hydroxyl group was substituted by the methyl, isopropyl, hexyl, and benzyl moieties, has been investigated using Broadband dielectric (BD), Nuclear magnetic resonance (NMR), and Raman spectroscopies. We found that except for benzyl IBU (Ben-IBU), an additional process (slow mode, SM) appears in dielectric spectra in all examined compounds. It is worth noting that this relaxation process was observed for the first time in non-modified IBU (a Debye relaxation). According to suggestions by Affouard and Correia [J. Phys. Chem. B. 114, 11397 (2010)] as well as further studies by Adrjanowicz et al. [J. Chem. Phys. 139, 111103 (2013)] on Met-IBU, it was attributed to synperiplanar-antiperiplanar conformational changes within the molecule. Herein, we have shown that with an increasing molecular weight of the substituent, the relaxation times of the SM become longer and its activation energy significantly increases. Moreover, this new relaxation mode was found to be broader than a simple Debye relaxation in Iso-IBU and Hex-IBU. Additional complementary NMR studies indicated that either there is a significant slowdown of the rotation around the O=C-O-R moiety or this kind of movement is completely suppressed in the case of Ben-IBU. Therefore, the SM is not observed in the dielectric loss spectra of this compound. Finally, we carried out isothermal experiments on the samples which have a different thermal history. Interestingly, it turned out that the relaxation times of the structural processes are slightly shorter with respect to those obtained from temperature dependent measurements. This effect was the most prominent in the case of Hex-IBU, while for Ben-IBU, it was not observed at all. Additional time-dependent measurements revealed the ongoing equilibration manifested by the continuous shift of the structural process, until it finally reached its equilibrium position. Further Raman investigations showed that this effect may be related to the rotational/conformational equilibration of the long hexyl chains. Our results are the first ones demonstrating that the structural process is sensitive to the conformational equilibration occurring in the specific highly viscous systems.

The spectroscopic studies of humic acid extracted from sediment collected at different seasons.

Goczalkowice Reservoir is the biggest water reservoir in the south of Poland. For our studies bottom sediments were collected from eight different places of the reservoir at various seasons of the year. EPR spectroscopy was applied to analyse both quantitatively and qualitatively the humic acids (HA) present in the samples. EPR spectra of the extracted HA exhibited broad lines from the paramagnetic metal ions and narrow lines from free radicals. The values of the free radical concentration obtained for HA amounted to 1.14-13.6 × 1016 spin g(-1) depending on the season and the place of sample collection. The values of the g factor obtained for HA were of the range 2.0027-2.0035. The EPR studies show that HA extracted from bottom sediment collected at various points of the Goczalkowice Reservoir exhibit similar physical-chemical properties. It was also observed that the depth of the reservoir affects the content of the oxygen functional groups as well as the free radical concentration in HA. The identification of the functional groups was done by means of IR. UV/VIS spectroscopy was used to estimate the maturity of the HA.

Comparison of humification processes occurring during sewage purification in treatment plants with different technological processes.

The course of the humification process of sewage sludge collected from three biologic-mechanical treatment plants with different treatment technologies was studied. The maturity of sewage sludge and its usefulness for agricultural purposes was also discussed. The physical-chemical properties of humic acids extracted from sewage sludge received from comparable stages of sludge purification were described. Changes of the sludge properties during sewage purification and the progress of the humification process were investigated with EPR, IR and UV/VIS spectroscopic methods. The content of the elements and the carboxylic groups in humic acids extracted from each stage of the sewage treatment were also determined. It was found that the humification processes take place in all three treatment plants but with different intensities resulting from the differences in the individual cleaning processes in these plants. The most intensive changes of physical-chemical parameters in the extracted humic acids were observed in the anaerobic digester where mesophilic fermentation occurs. The sludge oxygenation processes also significantly affect the course of the humification process during sewage treatment.

NMR study of the humification process during sewage sludge treatment.

Humic acids, extracted from sludge at the biologic-mechanical sewage treatment plant in Jastrzebie Zdroj, have been investigated by means of (1)H, (13)C and (31)P NMR spectroscopy. Sludge samples for studies were taken from the primary settling tank, the nitrification chamber, the digestion chamber and the sludge drying beds. The (1)H NMR analysis of humic acid extracted from sludge at various stages of sewage treatment confirmed the presence of the functional groups that are characteristic for humic substances, and the analysis showed changes in their relative intensities. The (13)C NMR indicated that the aromatisation of the humic acid increased during sewage treatment. Moreover, the analysis of the (31)P NMR spectra allowed us to observe the changes in the phosphorus groups of the studied humic acids.

Influence of Surface-Active Trace Impurities on the Surface Properties of Aqueous Solutions of Oligoethylene Glycol Monooctyl Ethers.

In this paper the influence of surface-active trace impurities in aqueous oligoethylene glycol monooctyl ether solutions on their adsorption behavior at the air/water interface is considered. The equilibrium surface tension (final sigmae) vs logarithm of concentration (ln c) isotherms of surfactants when used "as received" usually reveal a broad concentration range characterized by a constant slope, dfinal sigmae/d ln c. This linear dependence of the equilibrium surface tension on the logarithm of the surfactant concentration is observed for various surfactants at various fluid interfaces, which contradicts the fundamental Gibbs equation given in Eq. [1]. The same behavior was also observed for aqueous solutions of chemically well-defined oligoethylene glycol monooctyl ethers. In this case the paradoxical behavior did vanish after purification of aqueous solutions until the state of "surface-chemical purity" was reached using an apparatus for programmed high-performance purification of surfactant solutions. The gas chromatographic analyses of the original samples used showed that they contained impurities of different chemical structure and surface activity. Analysis of material aspirated from the surface of these alcohol ethoxylate solutions indicates that these trace impurities are enriched or impoverished at the solution's surface. A clear correlation between the surface activity parameter and the enrichment/impoverishment was found. Thus, these findings prove that the paradoxical adsorption behavior (dfinal sigmae/d ln c = constant) of the oligoethylene glycol monooctyl ethers is caused by surface-active trace impurities. These results support the hypotheses suggested by K. Lunkenheimer and Ch. Wedler [Tenside, Surfactants, Detergents 30, 342 (1993)] that generally it is the effect of surface-active trace impurities that gives rise to paradoxical adsorption behavior with surfactant systems at fluid interfaces. Copyright 1998 Academic Press.

Alkaloids from Hippeastrum equestre. Part I. Phamine, a new phenanthridone alkaloid.

From the bulbs of Vietnamese Hippeastrum equestre Herb. (Amaryllidaceae), besides the well known alkaloids lycorine, tazettine, and hippeastrine, a new alkaloid, phamine, has been isolated. Its structure was established by spectroscopic methods.

Monitoring glucocorticoid therapy: a pharmacokinetic approach.

Although glucocorticoid therapy is essential for the treatment of severe inflammatory disorders, there is no systematic approach to patient variables that may affect availability of a steroid dose. After the development of a data base of pharmacokinetic parameters, we examined glucocorticoid pharmacokinetics in 54 patients between 2 and 70 years of age using 70 pharmacokinetic studies after administration of intravenous methylprednisolone (n = 25), oral methylprednisolone (n = 15), intravenous prednisolone (n = 18), and oral prednisone (n = 12). Eleven patients had unusually rapid methylprednisolone elimination (clearance, 565 to 837 ml/min/1.73 m2; population mean, [+/- SD] 380 +/- 100 ml/min/1.73 m2) without an identifiable cause. Incomplete absorption of methylprednisolone and prednisone was observed in three patients and one patient, respectively. Evaluation of glucocorticoid pharmacokinetics in children aged 1 year 8 months to 18 years demonstrated a significant inverse correlation (r = 0.88; p less than 0.001) between prednisolone clearance and age. It is therefore important to consider age in the interpretation of pharmacokinetic data. To simplify measurement of prednisolone clearance, a single-dose single-point method was developed. This was based on a highly significant relationship between the 6-hour postdose prednisolone concentration and prednisolone clearance (log prednisolone clearance = 2.66 + [6-hour postdose concentration] [-0.00167]; r2 = 0.96; p less than 0.0001). Evaluation of glucocorticoid pharmacokinetics in the clinical setting can be used to identify abnormalities in absorption, elimination, and patient compliance. This technique can be used to individualize glucocorticoid dosing regimens.

[Biotransformation of phenolglycosides leiocarposide and salicin]. / Biotransformation der Phenolglycoside Leiocarposid und Salicin.

Leiocarposide (1; 3-beta-D-glucopyranosyloxy-2-methoxy-6-hydroxy-benzoic acid -2'-beta-D-glucopyranosyloxybenzyl ester) is a phenolic glycoside from Solidago virgaurea L. After oral administration to rats it will be only poorly absorbed and mostly unchanged fecaly excreted. In the urine were found less than 10% as metabolites: leiocarpic acid (3; 3,6-dihydroxy-2-methoxy-benzoic acid, 2% of the administered dose), 3-conjugates (2%), salicylic acid (5; 0.5%), 5-conjugates (0.1%) and salicyluric acid (6; 0.5%). On the other hand salicin (2), structural part of 1, is good absorbed. In the urine were excreted 15% of the unchanged drug and the following metabolites: 0.1% saligenin (4), 30% 5, 5% 5-conjugates, 0.1% 6, 2% gentisic acid (7) and 0.1% 2,3-dihydroxy-benzoic acid (8). The different metabolic rates are explicable by the high stability of the ester bond of 1. It is hydrolyzed in artificial intestinal fluid only very slowly (t1/2 = 41.7 h).

Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy.

Prednisolone and methylprednisolone pharmacokinetic parameters were evaluated in asthmatic children receiving concomitant anticonvulsant therapy. On separate study days, 15 children receiving either phenobarbital, carbamazepine, phenytoin, or combination anticonvulsant therapy were administered an intravenous dose of prednisolone or methylprednisolone and compared with a pediatric population not receiving anticonvulsant therapy. Plasma clearance of prednisolone in subjects receiving phenobarbital, carbamazepine, and phenytoin and in control subjects was 302.7 +/- 74.6, 383.2 +/- 53.8, 378.9 +/- 50.7, and 214.0 +/- 28.8 ml/min/1.73 m2 (mean +/- 1 SD), whereas plasma clearance of methylprednisolone was 1179.1 +/- 519.4, 1687.0 +/- 109.9, 2209.5 +/- 473.8, and 381.7 +/- 98.4 ml/min/1.73 m2, respectively. Bioavailability of prednisolone after the oral administration of prednisone and methylprednisolone ranged from 86% to 104% during anticonvulsant therapy. Three individuals reevaluated 13 to 20 days after discontinuing anticonvulsant therapy demonstrated pharmacokinetic parameters similar to those of the control group. Limited studies performed in patients receiving combination anticonvulsant therapy did not demonstrate an additive effect on prednisolone elimination. Differences in the degree of enhancement of prednisolone and methylprednisolone disposition in all three anticonvulsant study groups suggest that different metabolic pathways may be involved.

Corticosteroid therapy in adolescent patients.

Since their introduction in the 1950s, corticosteroids have become an important adjunct in the therapy for a wide variety of diseases. Improved guidelines for clinical applications and for reduction in undesirable effects have been achieved through a better understanding of corticosteroid mechanisms of action and pharmacokinetic properties. This discussion will review the indications and adverse effects associated with corticosteroid therapy. Emphasis will be placed on the important aspects of corticosteroid therapy in adolescent patients including recent advances essential to the development of guidelines for dosing and therapeutic monitoring.