Alkali metal salts of rutin - Synthesis, spectroscopic (FT-IR, FT-Raman, UV-VIS), antioxidant and antimicrobial studies.

In this work several metal salts of rutin with lithium, sodium, potassium, rubidium and cesium were synthesized. Their molecular structures were discussed on the basis of spectroscopic (FT-IR, FT-Raman, UV-VIS) studies. Optimized geometrical structure of rutin was calculated by B3LYP/6-311++G(∗∗) method and sodium salt of rutin were calculated by B3LYP/LanL2DZ method. Metal chelation change the biological properties of ligand therefore the antioxidant (FRAP and DPPH) and antimicrobial activities (toward Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumonia, Candida albicans and Saccharomyces cerevisiae) of alkali metal salts were evaluated and compared with the biological properties of rutin.

Theoretical (in B3LYP/6-3111++G** level), spectroscopic (FT-IR, FT-Raman) and thermogravimetric studies of gentisic acid and sodium, copper(II) and cadmium(II) gentisates.

The DFT calculations (B3LYP method with 6-311++G(d,p) mixed with LanL2DZ for transition metals basis sets) for different conformers of 2,5-dihydroxybenzoic acid (gentisic acid), sodium 2,5-dihydroxybenzoate (gentisate) and copper(II) and cadmium(II) gentisates were done. The proposed hydrated structures of transition metal complexes were based on the results of experimental findings. The theoretical geometrical parameters and atomic charge distribution were discussed. Moreover Na, Cu(II) and Cd(II) gentisates were synthesized and the composition of obtained compounds was revealed by means of elemental and thermogravimetric analyses. The FT-IR and FT-Raman spectra of gentisic acid and gentisates were registered and the effect of metals on the electronic charge distribution of ligand was discussed.

Spectroscopic (FT-IR, FT-Raman, 1H, 13C NMR, UV/VIS), thermogravimetric and antimicrobial studies of Ca(II), Mn(II), Cu(II), Zn(II) and Cd(II) complexes of ferulic acid.

The molecular structure of Mn(II), Cu(II), Zn(II), Cd(II) and Ca(II) ferulates (4-hydroxy-3-methoxycinnamates) was studied. The selected metal ferulates were synthesized. Their composition was established by means of elementary and thermogravimetric analysis. The following spectroscopic methods were used: infrared (FT-IR), Raman (FT-Raman), nuclear magnetic resonance ((13)C, (1)H NMR) and ultraviolet-visible (UV/VIS). On the basis of obtained results the electronic charge distribution in studied metal complexes in comparison with ferulic acid molecule was discussed. The microbiological study of ferulic acid and ferulates toward Escherichia coli, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris was done.

Spectroscopic (FT-IR, FT-Raman and 1H and 13C NMR) and theoretical in MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p) levels study of benzenesulfonic acid and alkali metal benzenesulfonates.

The FT-IR, FT-Raman and NMR ((1)H and (13)C) spectra of benzenesulfonic acid as well as lithium, sodium, potassium, rubidium and caesium benzenesulfonates were registered, assigned and compared. The molecular structures of ligand and alkali metal salts were discussed. On the basis of quantum mechanical calculations in MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p) levels the geometric parameters, infrared spectra, NMR spectra, the magnetic and geometric aromaticity indices for acid and alkali metal benzenesulfonates and benzoates were obtained. The effect of alkali metal ions on the electronic charge distribution of benzenesulfonic acid was studied and compared with the alkali metal benzoates and benzoic acid.

Mn(II), Cu(II) and Cd(II) p-coumarates: FT-IR, FT-Raman, ¹H and ¹³C NMR and thermogravimetric studies.

Manganese(II), copper(II) and cadmium(II) complexes of p-coumaric acid (p-hydroxycinnamic acid) were synthesized. Their composition was established by means of elementary and thermogravimetric analysis. To study the molecular structure of synthesized compounds many miscellaneous analytical methods, which complement one another, were used: infrared (FT-IR), Raman (FT-Raman) and nuclear magnetic resonance ((1)H, (13)C NMR). The spectroscopic studies lead to conclusions concerning the distribution of the electronic charge in complexes in comparison with p-coumaric acid molecule and the type of metal ion coordination.

Relationship between chemical structure and biological activity of alkali metal o-, m- and p-anisates. FT-IR and microbiological studies.

In this work we investigated relationship between molecular structure of alkali metal o-, m-, p-anisate molecules and their antimicrobial activity. For this purpose FT-IR spectra for lithium, sodium, potassium, rubidium and caesium anisates in solid state and solution were recorded, assigned and analysed. Microbial activity of studied compounds was tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris. In order to evaluate the dependency between chemical structure and biological activity of alkali metal anisates the statistical analysis (multidimensional regression and principal component) was performed for selected wavenumbers from FT-IR spectra and parameters that describe microbial activity of anisates. The obtained statistical equations show the existence of correlation between molecular structure of anisates and their biological properties.

Postural sway in children and young adults, survivors of CNS tumours.

PURPOSE: Brain tumours are the most common solid tumours in children and adolescents. The increasing survival rate of these patients makes their follow-up and quality of life assessment an important task. The evaluation of the negative influence of anti-cancer treatment on their balance is the aim of this study. MATERIAL AND METHODS: The balance assessment was performed on patients who completed the treatment of CNS tumours and were disease-free at the time of the study. Eighty-eight patients aged 5 to 24 years participated in the study. Postural sway was recorded using Kistler force plate. Balance test parameters from two conditions: eyes open and eyes closed were calculated and compared with reference data. The severity of the balance disorders was scored for both conditions. RESULTS: The balance disorders were generally not dependent on the localisation of the tumour. Only patients treated for posterior fossa tumours had a higher score (indicating pronounced balance deficit) in eyes closed condition comparing to others. The patients treated for spinal cord tumours seemed to have increased total sway path in comparison to others. The severity of the balance deficits tended to diminish in time. CONCLUSIONS: These results suggest that the repair mechanisms of the CNS could overcome the problems inflicted by the illness and therapy.

Spectroscopic (FT-IR, FT-Raman, UV) and microbiological studies of di-substituted benzoates of alkali metals.

The FT-IR, FT-Raman and UV spectra of 3,5-dihydroxybenzoic and 3,5-dichlorobenzoic acids as well as lithium, sodium, potassium, rubidium, caesium 3,5-dihydroxy- and 3,5-dichlorobenzoates were recorded, assigned and compared. The theoretical geometries, Mulliken atomic charges, IR wavenumbers were obtained in B3LYP/6-311++G** level. On the basis of the gathered experimental and theoretical data the effect of metals and substituents on the electronic system of studied compounds were investigated. Moreover, the antimicrobiological activity of studied compounds against two species of bacteria: Bacillus subtilis, Staphylococus aureus and one species of yeast: Candida albicans were studied after 24 and 48 h of incubation. The attempt was made, to find out whether there is any correlation between the first principal component and the degree of growth inhibition exhibited by studied compounds in relation to selected microorganisms.

Experimental (FT-IR, FT-Raman, 1H NMR) and theoretical study of magnesium, calcium, strontium, and barium picolinates.

The experimental IR, Raman, and 1H NMR spectra of picolinic acid, as well as magnesium, calcium, strontium, and barium picolinates were registered, assigned and studied. Characteristic changes in the spectra of metal picolinates in comparison with the spectrum of ligand were observed, which lead to the conclusion that perturbation of the aromatic system of picolinates increases along with the series Mg-->Ca-->Sr-->Ba. Theoretical structures of beryllium and magnesium picolinates, as well as theoretical IR spectrum of magnesium picolinate were calculated in B3PW91/6-311++G(d, p) level. On the basis of calculated bond lengths in pyridine ring geometric, aromaticity indexes HOMA were calculated. The idea of these indexes is based on the fact that the essential factor in aromatic stabilization is the pi delocalization manifested in: planar geometry, equalization of the bond lengths and angles, and symmetry. The decidedly lower value of HOMA for magnesium picolinate (i.e. 0.545; 0.539) than that for beryllium picolinate (i.e. 0.998; 0.998) indicate higher aromatic properties of Be picolinate than of Mg picolinate. The comparison of theoretical and literature experimental structures of magnesium picolinate was done. The experimental structure contains two water molecules, so the calculations for hydrated magnesium picolinate were carried on, and the influence of coordinated water molecule on the structure of picolinates was discussed. The HOMAs for hydrated experimental and calculated Mg picolinate amount to 0.870; 0.743, and 0.900; 0.890, respectively, whereas for anhydrous structure, it is as described above, i.e. 0.545; 0.539. Thus, the calculations clearly showed that water molecules coordinated to the central atom weakens the effect of metal on the electronic system of ligand.

Regulation of the human apoptotic DNase/RNase endonuclease G: involvement of Hsp70 and ATP.

Endonuclease G (EndoG) is a mitochondrial enzyme that becomes an apoptotic nuclease when released from the mitochondrial intermembrane space. EndoG will digest either DNA or RNA, but at physiological ionic strength, RNA is a much more favorable substrate as compared to chromatin. This indicates that EndoG's major in vivo function(s) may be: (i) an apoptotic RNase, and/or (ii) an apoptotic DNase in the presence of additional co-activators. In the present study we have searched for factors that modulate the activity of human EndoG on DNA substrates. We demonstrate that EndoG forms complexes with AIF and FEN-1 but not with PCNA. Interestingly, heat shock proteins 70 interact with EndoG and are involved in the regulation of its activity. Purified Hsp70 prevented stimulation of EndoG DNase activity by other nuclear factors in the ATP-dependent manner.

The influence of metals on the electronic system of biologically important ligands. Spectroscopic study of benzoates, salicylates, nicotinates and isoorotates. Review.

This paper reviews the results of the intense experimental and theoretical studies on the influence of selected metals on the electronic system of biologically important molecules such as benzoic, 2-hydroxybenzoic and 3-pyridine carboxylic acids as well as 5-carboxyuracil. The research involved following techniques: infrared (FT-IR), Raman (FT-Raman), FT-IR Ar matrix, electronic absorption spectroscopy (UV/visible), nuclear magnetic resonance ((1)H, (13)C, (15)N, (17)O NMR), X-ray and quantum mechanical calculations. The influence of metals on the electronic system was examined through comparison of the changes in so called "logical series". The exemplary series are: Li-->Na-->K-->Rb-->Cs, Na(I)-->Ca(II)-->La(III)-->Th(IV); Na(I)-->Mg(II)-->Al(III) or long series of La(III) and fourteen lanthanides La(III)-->Ce(III)-->Lu(III). The correlation between the perturbation of the electronic system of ligands and the position of metals in the periodic table was found. The influence of the carboxylic anion structure and the effect of hydration on the perturbation of the electronic system of molecule were also discussed. The partial explanation in what way metals disturb and stabilize electronic system of studied ligands was done. It is necessary to carry out the physico-chemical studies of benzoates, salicylates, 3-pyridine carboxylates and isoorotates in order to understand the nature of the interactions of these compounds with their biological targets (e.g., receptors in the cell or important cell components). The results of this study make possible to predict some properties of a molecule, such as its reactivity, durability of complex compounds, and kinship to enzymes.

A review of selected anti-tumour therapeutic agents and reasons for multidrug resistance occurrence.

It is assumed that proteins from the ABC family (i.e., glycoprotein P (Pgp)) and a multidrug resistance associated protein (MRP) play a main role in the occurrence of multidrug resistance (MDR) in tumour cells. Other factors that influence the rise of MDR are mechanisms connected with change in the effectiveness of the glutathione cycle and with decrease in expression of topoisomerases I and II. The aim of this review is to characterize drugs applied in anti-tumour therapy and to describe the present state of knowledge concerning the mechanisms of MDR occurrence, as well as the pharmacological agents applied in reducing this phenomenon.

The influence of selected metals on the electronic system of biologically important ligands.

The influence of (i) halogens, (ii) different alkaline cations, Li(I), Na(I), K(I), Rb(I) and Cs(I), and (iii) lanthanide cations, Pr(III), Nd(III), Dy(III) and Er(III) on the electronic structure of the aromatic ring as well as of the carboxylic anion of the substituted benzoic acids was investigated. Systematic change (decrease or increase) in the wavenumbers of selected bands along the F-->Cl-->Br-->I series was observed. This change correlates in linear fashion with a decrease in the ionic potential of the halogens. A shift of the selected bands along with the alkaline and the lanthanide metal series was also observed and correlated with the ionic potential of the metal. It was noticed that the increase in the ionic potential of halogen atoms causes a remarkable increase in the difference (Deltanu) between the wavenumbers of nuasym(COO-) and nusym(COO-). Among the halogens the ionic potential is the lowest for iodine and this substituent brings about maximal proximity of the asymmetric and symmetric bands of the carboxylic anion. The change of cation in the molecule causes a characteristic change in the difference (Deltanu) between the wavenumbers of nuasym(COO-) and nusym(COO-) as well. Along with the lanthanide series under study (Pr-->Nd-->Dy-->Er) this difference decreases, while between alkaline cations lithium broadens these bands to the highest degree. The influence of the alkaline and the lanthanide cations on the vibrational structure of the whole molecule was analysed and compared.

Phospholipids modulate the substrate specificity of soluble UDP-glucose:steroid glucosyltransferase from eggplant leaves.

UDP-glucose-dependent glucosylation of solasodine and diosgenin by a soluble, partially purified enzyme fraction from eggplant leaves is affected in a markedly different way by some phospholipids. While glucosylation of diosgenin and some closely related spirostanols, e.g. tigogenin or yamogenin, is strongly inhibited by relatively low concentrations of several phospholipids, the glucosylation of solasodine is unaffected or even slightly stimulated. These effects depend both on the structure of the polar head group and the nature of the acyl chains present in the phospholipid. The most potent inhibitors of diosgenin glucosylation are choline-containing lipids: phosphatidylcholine (PC) and sphingomyelin (SM) but the removal of phosphocholine moiety from these phospholipids by treatment with phospholipase C results in an almost complete recovery of the diosgenin glucoside formation by the enzyme. Significant inhibition of diosgenin glucoside synthesis and stimulation of solasodine glucosylation was found only with PC molecular species containing fatty acids with chain length of 12-18 carbon atoms. PC with shorter or longer acyl chains had little effect on glucosylation of either diosgenin or solasodine. Our results indicate that interaction between the investigated glucosyltransferase and lipids are quite specific and suggest that modulation of the enzyme activity by the nature of the lipid environment may be of importance for regulation of in vivo synthesis of steroidal saponins and glycoalkaloids in eggplant.

UDP-glucose:solasodine glucosyltransferase from eggplant (Solanum melongena L.) leaves: partial purification and characterization.

Uridine 5'-diphosphoglucose-dependent glucosyltransferase which catalyzes the glycosylation of solasodine i.e. UDP-glucose:solasodine glucosyltransferase, is present in leaves, roots, unripe fruits and unripe seeds of eggplant (Solanum melongena L.). The glucosylation product is chromatographically identical with authentic solasodine 3 beta-D-monoglucoside, a putative intermediate in the biosynthesis of solasodine-based glycoalkaloids characteristic of the eggplant. The enzyme was purified about 50-fold from crude cytosol fraction of eggplant leaves by ammonium sulphate precipitation and column chromatography on Q-Sepharose and Sephadex G-100. The native enzyme has a molecular mass of approx. 55 kDa and pH optimum of 8.5. Divalent metal ions are not required for its activity but the presence of free-SH groups is essential. Besides solasodine (Km = 0.04 microM), the enzyme effectively glucosylates tomatidine, another steroidal alkaloid of the spirosolane type, but it is virtually inactive towards the solanidane-type steroidal alkaloids such as solanidine or demissidine. The enzyme is specific for UDP-glucose (Km = 2.1 microM) since unlabelled ADP-, GDP-, CDP- or TDP-glucose could not effectively compete with UDP-[14C]glucose used as the sugar donor for solasodine glucosylation. Moreover, no synthesis of labelled solasodine galactoside was observed when UDP-[14C]glucose was replaced with UDP-[14C]galactose.

Application of biomechanical growth models of the quantitative evaluation of the motor system in children.

To evaluate the effectiveness of rehabilitation methods, and to assess the progress of the rehabilitation process in an individual patient, quantitative methods are necessary. The large number of motor system parameters makes the problem of data collection time-consuming and expensive. A quantitative evaluation of the child's motor system is an assessment of a combination of the growth and rehabilitation processes. The aim of the study was to establish methods of differentiation between these two processes. The chosen anthropometric measures, biomechanical parameters of the lower leg segment, maximal voluntary extension and flexion torques of lower leg and chosen gait parameters, were measured in various groups of healthy children 6-18 years old. Mathematical functions were calculated describing these parameters against developmental parameters (body mass, body stature, age). Using the maximal correlation criterion the best growth parameters were established. Normalized databases for these parameters were developed. It is suggested that, using their approach, differentiation between the influences of growth and rehabilitation processes can be achieved, thus eliminating the need for tedious data collection.

The structural requirements of sterols for membrane function in Saccharomyces cerevisiae.

Cultures of Saccharomyces cerevisiae strain GL7 auxotrophic for sterol were incubated with a series of sterols and sterol-like molecules (tetracyclic and pentacyclic triterpenoids) in order to determine the structural requirements of sterols for bulk membrane function. For growth support, the 3 beta-OH group could not be replaced by H, OMe, OBu, NH2, NHOH, OAc, keto, or 3 alpha-OH. A methyl group at C-14 was neither deleterious nor essential for activity. Removal of the C-4 geminal methyl group was obligatory for activity. Thus, no sterol-like triterpenoid supported growth (e.g., tetrahymanol, lanosterol, and cycloartenol). Growth support required a sterol with the longest methylene segment extending from C-20 not to exceed six contiguous C-atoms and the stereochemistry must be C-20 R. No significance could be attributed to branching at C-20 (i.e., to C-21), C-24 (when alkylated), or C-25 (regarding the isopropyl group). Double bonds in the nucleus were not essential for activity since cholestanol supported growth. In several incubations, the addition of trace levels of dietary ergosterol (0.5 microgram/ml) to the medium was necessary to promote growth and transformation of the bulk sterol to a membrane competent sterol(s).

Regulation of sterol biosynthesis in sunflower by 24(R,S),25-epiminolanosterol, a novel C-24 methyl transferase inhibitor.

Whereas sitosterol and 24(28)-methylene cycloartanol were competitive inhibitors (with Ki = 26 microM and 14 microM, respectively), 24(R,S)-25-epiminolanosterol was found to be a potent non-competitive inhibitor (Ki = 3.0 nM) of the S-adenosyl-L-methionine-C-24 methyl transferase from sunflower embryos. Because the ground state analog, 24(R,S)-oxidolanosterol, failed to inhibit the catalysis and 25-azalanosterol inhibited the catalysis with a Ki of 30 nM we conclude that the aziridine functions in a manner similar to the azasteriod (Rahier, A., et al., J. Biol. Chem. (1984) 259, 15215) as a transition state analog mimicking the carbonium intermediate found in the normal transmethylation reaction. Additionally, we observed that the aziridine inhibited cycloartenol metabolism (the preferred substrate for transmethylation) in cultured sunflower cells and cell growth.

Characterization of acyllipid: sterol glucoside acyltransferase from oat (Avena sativa L.) seedlings.

Membranous fractions from leaves of oat seedlings readily convert cholesterol beta-D-glucoside into its 6'-O-acyl derivative using endogenous acyllipids as acyl sources. Experiments with delipidated enzyme preparations showed that among acyllipids present in oat leaves digalactosyldiacylglycerols are evidently the best acyl donors in this reaction. Beside of sterol glucosides, the enzyme can acylate beta-D-glucosides of several other steroids, although at very different rates.