Curcumin as tyrosine kinase inhibitor in cancer treatment.

Curcumin is a natural substance known for ages, exhibiting a multidirectional effect in cancer prevention and adjuvant cancer therapies. The great advantage of using nutraceuticals of vegetable origin in comparison to popular cytostatic drugs is the minimized side effect and reduced toxicity. The targets in oncological therapy are, among others, tyrosine kinases, important mediators of signaling pathways whose impaired expression is observed in many types of cancer. Unfortunately, the hydrophobic nature of the curcumin molecule often limits its bioavailability, which is why many studies focus on the chemical modification of this compound. Current research is aimed at modifying structures that improve the pharmacokinetic parameters of curcumin, e.g. the formation of nanoparticles, complexes with metals or the synthesis of curcumin derivatives with functional substituents that allow tumor targeting. The article is a review and analysis of current literature on the properties of curcumin and its derivatives in the treatment of cancers directed to signaling pathways of tyrosine kinases and confronts the problem of low assimilation of curcumin with potential therapeutic effects.

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.

Tetrad effect in the adsorption of the lanthanides on zeolite Y.

The adsorption of the lanthanides (except for Pm) on the zeolite Y was investigated under various solution conditions of nitrate ion concentration ([NO(-)(3)]: 0.001-2 mol/dm(3)) and total lanthanide concentration (from 0.0001 to 0.001 mol/dm(3)). The solutions of the lanthanide nitrates were equilibrated with the zeolite samples at 296 K. The concentrations of lanthanides in the initial and equilibrium solutions were determined by means of spectrophotometrical method with Arsenazo III reagent and distribution constants K(d) of the lanthanides between aqueous and zeolite phases were calculated. The evident concave tetrad effect in the change of logK(d) values (nitrate concentrations 0.4-2 mol/dm(3)) within the lanthanide series was noticed and an attempt at its explanation through the comparison of covalence in LnO bonds existing in triple bond AlO(1/3Ln)Si triple bond species in the zeolite phase and in Ln(NO(3))(2+) complexes forming in the aqueous phase was presented. The weak convex tetrad effect for equilibrium nitrate concentrations 0.001-0.32 mol/dm(3), manifesting in the change of logK(d) values and in the alteration of logK (adsorption constants), is evidence of the complexation of the tripositive lanthanide ions by the oxygens originating both from water molecules and from the zeolite framework.

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.

Reversible switching of structural and plasmonic properties of liquid-crystalline gold nanoparticle assemblies.

Hybrid materials built of spherical gold nanoparticles with three different sizes covered with (pro)mesogenic molecules have been prepared. Small-angle X-ray diffraction studies showed that after thermal annealing most of the obtained materials formed long-range ordered assemblies. Variation of the (pro)mesogenic ligand architecture enabled us to achieve a switchable material, which could be reversibly reconfigured between 3D long-range ordered structures with tetragonal and face centred cubic symmetries. This structural reconfiguration induces changes to the plasmonic response of the material. This work demonstrates that it is possible to use LC-based self-assembling phenomena to prepare dynamic materials with structural properties important for the development of active plasmonic metamaterials.

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.

Molecular structure of 3-aminobenzoic acid complexes with alkali metals.

The vibration (FT-IR, FT-Raman), electronic (UV-Vis) and NMR (1H and 13C) spectra for 3-aminobenzoic acid and its alkali metal salts were recorded. The influence of lithium, sodium, potassium, rubidium and cesium on the electronic system of the 3-aminobenzoic acid was studied. The assignment of the vibration spectra was done. Characteristic shifts of band wavenumbers and changes in band intensities along the metal series were observed. Good correlation between the wavenumbers of the vibrational bands in the IR and Raman spectra for 3-aminobenzoates and ionic potential, electronegativity, atomic mass and affinity of metal cations were found. The chemical shifts of protons (1H NMR) and carbons (13C NMR) in the series of studied alkali metals were also observed. Optimized geometrical structures of studied compounds were calculated by ab initio and density functional methods.

The relationship between chemical structure and antimicrobial activity of selected nicotinates, p-iodobenzoates, picolinates and isonicotinates.

Alkaline metal, calcium and magnesium p-iodobenzoates and alkaline metal nicotinates, as well as sodium and potassium picolinic and isonicotinates were investigated by means of their antimicrobial and chemical properties. The quality estimation of the influence of metal cation coordinated to the carboxylic anion of the series of studied compounds on their antimicrobial activity as well as on the vibrational structure of whole complex in water solution was done. The changes in antimicrobial properties and in charge distribution of the complex along the position of nitrogen atom in the aromatic ring in sodium and potassium complexes were investigated. The analysis of influence of iodine substituent in para position on the change of electronic charge distribution of carboxylate anion and aromatic ring was done. The relationship between electronic properties estimated by vibrational spectroscopy and antimicrobial activity of studied complexes was investigated.

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.

The influence of selected metals and halogens on the electronic system of benzoic acid.

The influence of halogens and metals on the electronic system of the aromatic ring in lithium, sodium and potassium complexes with p-halogenobenzoic acids has been investigated by means of (13)C and (1)H NMR, IR and Raman spectroscopy and semi-empirical calculations. It has been shown that ionic potentials and electronegativities of halogens and metals are the main factors responsible for perturbations of the electronic charge distribution in the ring.

Application of experimental (FT-ICR) and theoretical (AM1) methods to the study of proton-transfer reactions for tautomerizing amidines in the gas phase.

Semiempirical calculations (AM1) together with experimental mass spectrometric (FT-ICR) data indicate the imino nitrogen atom as the favoured site of protonation and the amino nitrogen atom as the site of deprotonation of the amidine group in the gas phase. For tautomerizing N-methyl-N'-phenylbenzamidine the tautomer with the phenyl group at the imino nitrogen atom weakly predominates in tautomeric mixture.

m-Iodobenzoic acid complexes with selected metals: molecular structure and antimicrobial activity.

Complexes of lithium, sodium, potassium, rubidium, cesium, magnesium, calcium, manganese, and zinc with m-iodobenzoic acid were studied. The FT-IR and FT-Raman spectra of the mentioned compounds in the solid state and water solutions were recorded and analyzed. Principal component analysis (PCA) was performed on the wavenumbers of selected bands (eight bands) occurring in the vibrational spectra. The numbers obtained as a result of this procedure characterize the electronic properties of the molecule of each complex. The antimicrobial activity of the studied compounds against selected bacteria (Escherichia coli and Bacillus subtilis) and yeast (Saccharomyces cerevisiae and Hansenula anomala) was estimated. The relationship between the chemical properties (as characterized by PCA of the IR spectra) and antimicrobial properties of the compounds was examined, and a good correlation between the two factors was found.

Mechanisms of transport across cell membranes of complexes contained in antitumour drugs.

Various mechanism of antitumour drug transport across cell membranes has been described. Particular attention has been paid to a passive transport, active transport and multidrug resistance of complexes contained in antitumour drugs. A drug supply to the target site depends on the blood circulation within the tumour, on characteristic drug diffusion in the tissue, and also on binding protein. The physiologic transfer of hydrophilic compounds across the membrane is usually intermediated by means of a specific receptor or a carrier in that membrane, which facilitates the transport of compounds to and from the cell. Some drugs, e.g. doxorubicin and annamycin, can pass across the membrane by intermediacy of liposomes which exhibit a great activity in penetrating into tumour cells. The efficiency of antitumour drugs is limited by the appearance of resistance, i.e. by the lack of sensitivity of the cell to the administered drug. The presence in the membrane of specific proteins belonging to the ABC carriers group is postulated in a resistance theory; they would be responsible for 'pumping out' lipophilic drug molecules from the cell. Participation of high-energy ATP molecule is required by P-glycoprotein (Pgp) and by MRP protein described in this paper for their action. The mechanisms that are responsible for the cell resistance to drugs have been presented by analysing the resistance to antimetabolites, particularly to folate and fluoropyrimidine analogues, to alkylating agents, e.g. cisplatinum, and to heterocyclic compounds being responsible for so-called multidrug resistance.

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.

Vibration in metal and non-metal incubators.

The purpose of this study was to determine the amount of vibration transmitted to the surface of an incubator mattress. Empty incubators with metal (n = 12) and non-metal (n = 12) bases were monitored for vibration levels when the incubators were turned "off" and when they were turned "on." High levels of low-frequency vibration were detected in both types of incubators in both conditions. The metal incubators transmitted significantly less vibration to the mattress than did the non-metal incubators at several frequencies in the "off," the "on," and the "adjusted" conditions. These results suggest that infants experience significant whole-body vibration while lying in incubators.

Molecular structure and spectroscopic analysis of homovanillic acid and its sodium salt--NMR, FT-IR and DFT studies.

The estimation of the electronic charge distribution in metal complex or salt allows to predict what kind of deformation of the electronic system of ligand would undergo during complexation. It also permits to make more precise interpretation of mechanism by which metals affect the biochemical properties of ligands. Theinfluence ofsodium cation on the electronic system of homovanillic acid was studied in this paper. Optimized geometrical structures of studied compounds were calculated by B3LYP/6-311++G(**) method. Mulliken, MK and ChelpG atomic charges were analyzed. The theoretical NMR and IR spectra were obtained. (1)H and (13)C NMR as well as FT-IR and FT-Raman spectra of studied compounds were also recorded and analyzed. The calculated parameters are compared with experimental characteristics of these molecules.

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.

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.

Experimental and theoretical study of molecular structure of beryllium, magnesium, calcium, strontium and barium 4-nitrobenzoates.

The influence of alkaline earth metal ions on the electronic system of 4-nitrobenzoic acid was studied in this paper. The vibrational (FT-IR) and NMR ((1)H and (13)C) spectra were recorded for 4-nitrobenzoic acid (4-nba) and its salts (4-nb). The assignment of vibrational spectra was done. Some shifts of band wavenumbers in alkaline earth metal 4-nitrobenzoates spectra were observed in the series from magnesium to barium salts. Good correlations between wavenumbers of the vibrational bands in the IR spectra of studied salts and ionic potential, electronegativity, inverse of atomic mass, ionic radius and ionization energy of studied metals were found. The regular changes in the chemical shifts of protons ((1)H NMR) and carbons ((13)C NMR) in the series of studied salts were also observed. Optimized geometrical structures of studied compounds were calculated by B3LYP method using 6-311++G(**) as well as LANL2DZ basis sets. Theoretical wavenumbers and intensities in IR and chemical shifts in NMR spectra were also obtained. The calculated parameters were compared with experimental data of studied compounds.