Vapor Phosphorylation of Cellulose by Phosphorus Trichlo-Ride: Selective Phosphorylation of 6-Hydroxyl Function-The Synthesis of New Antimicrobial Cellulose 6-Phosphate(III)-Copper Complexes.

This research is focused on a synthesis of copper-cellulose phosphates antimicrobial complexes. Vapor-phase phosphorylations of cellulose were achieved by exposing microcrystalline cellulose to phosphorus trichloride (PCl3) vapors. The cellulose-O-dichlorophosphines (Cell-O-PCl2) formed were hydrolyzed to cellulose-O-hydrogenphosphate (P(III)) (Cell-O-P(O)(H)(OH)), which, in turn, were converted into corresponding copper(II) complexes (Cell-O-P(O)(H)(OH)∙Cu2+). The analysis of the complexes Cell-O-P(O)(H)(OH)∙Cu2+ covered: scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), atomic absorption spectrometry with flame excitation (FAAS), and bioactivity tests against representative Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). The antimicrobial tests of synthesized Cell-O-P(O)(H)(OH)∙Cu2+ revealed their potential applications as an antibacterial material.

Physicochemical and in vitro cytotoxicity studies of inclusion complex between gemcitabine and cucurbit[7]uril host.

Gemcitabine, a cytostatic drug from the pyrimidine antimetabolite group, exhibits limited storage stability and numerous side effects during therapy. One of the strategies to improve the effectiveness of therapy with such drugs is the use of supramolecular nano-containers, including dendrimers and macrocyclic compounds. The ability of gemcitabine to attach a proton in an aqueous environment necessitates the search for a carrier that is well-tolerated by an organism and capable of supramolecular binding of a ligand (drug) in a cationic form. In the current study a promising strategy was tested for using cucurbituril Q7 to bind gemcitabine cations for its efficient intracellular delivery on three selected cancer cell lines (MOLT4, THP-1 and U937). Based on physicochemical studies (equilibrium dialysis, UV and 1H NMR titrations, DOSY 1H NMR measurements, DSC calorimetry) and cytotoxicity tests on cells with a free and blocked hENT1 transporter, the conclusion was drawn about the binding and penetration of the cucurbituril-drug complex into cancer cells.

First thia-Diels-Alder reactions of thiochalcones with 1,4-quinones.

Aryl and hetaryl thiochalcones react smoothly with 1,4-quinones in THF solution at 60 °C yielding the corresponding fused 4H-thiopyrans after spontaneous dehydrogenation of the initially formed [4 + 2] cycloadducts. In general, the yields of the isolated products were high. With 5-chloro-10-hydroxy-1,4-anthraquinone, the thia-Diels-Alder reaction occurred with complete regioselectivity. In the case of the reaction of vitamin K3 (menadione) with diphenylthiochalcone, the initial cycloadduct was isolated in 37% yield.

Chromatographic and Computational Studies of Molecular Lipophilicity and Drug-likeness for few 2-Thioxo-1,3-Thiazolidin-4-one Derivatives and their Analogs.

Hydrophobicity of the eight 2-thioxo-1,3-thiazolidin-4-one derivatives was determined experimentally by thin-layer chromatography and predicted by means of commercially available programmers. RM values were determined by reversed-phase thin-layer chromatography with using acetonitrile-water, methanol-water, acetone-water, propan-2-ol-water or 1,4-dioxane-water and compared with logP values calculated by using computer programs: HyperChem 8.0.10, Virtual Chemical Calculation Laboratory, ACD/LogP. The drug-likeness has been calculated using Molinspiration. All the heterocycles were found to obey Lipinski's rule of 5 for an orally active drug.

1-(Acylamino)alkylphosphonic Acids-Alkaline Deacylation.

The alkaline deacylation of a representative series of 1-(acylamino)alkylphosphonic acids [(AC)-AAP: (AC) = Ac, TFA, Bz; AAP = GlyP, AlaP, ValP, PglP and PheP] in an aqueous solution of KOH (2M) was investigated. The results suggested a two-stage reaction mechanism with a quick interaction of the hydroxyl ion on the carbonyl function of the amide R-C(O)-N(H)- group in the first stage, which leads to instant formation of the intermediary acyl-hydroxyl adducts of R-C(O-)2-N(H)-, visible in the 31P NMR spectra. In the second stage, these intermediates decompose slowly by splitting of the RC(O-)2-N(H)- function with the subsequent formation of 1-aminoalkylphosphonate and carboxylate ions.

ß-Cyclodextrins incorporated multi-walled carbon nanotubes modified electrode for the voltammetric determination of the pesticide dichlorophen.

In this work, a glassy carbon electrode modified with ß-cyclodextrins and multi-walled carbon nanotubes (ß-CDs/MWCNTs/GCE) was constructed and applied for the square-wave adsorptive stripping voltammetric (SWAdSV) determination of the pesticide dichlorophen (Dcp). For the first time, this compound was electrochemically investigated. The voltammetric measurements were conducted in phosphate buffer (PBS) at pH 6.5 as a supporting electrolyte, and SWAdSV technique parameters were optimized. A linear calibration curve in the wide concentration range from 5.0 × 10-8molL-1 to 2.9 × 10-6molL-1 was obtained. Excellent analytical performance in terms of limit of detection (LOD) of 1.4 × 10-8molL-1 was achieved. The utility of the proposed method was verified by the quantitative analysis of Dcp in Pilica River water samples with satisfactory results. The characterization of modified electrodes was conducted by means of atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). Moreover, in this work, the dissociation constants (pKa) of Dcp using potentiometric pH titration were estimated. The stoichiometry of the Dcp-ß-CDs inclusion complex formed in solution was determined by proton nuclear magnetic resonance (1H NMR) spectroscopy, and a binding constant (ß2) was estimated from NMR titration studies.

Spectroscopic and calorimetric studies on the interaction between PAMAM G4-OH and 5-fluorouracil in aqueous solutions.

The results of spectroscopic measurements (an increase in solubility, equilibrium dialysis, 1H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate spontaneous (ΔG<0) binding of 5-fluorouracil molecules by PAMAM G4-OH dendrimer with terminal hydroxyl groups in an aqueous solution. PAMAM G4-OH dendrimer bonds about n=8±1 molecules of the drug with an equilibrium constant of K=70±10. The process of saturating the dendrimer active sites by the drug molecules is exothermal (ΔH<0) and is accompanied by an advantageous change in entropy (ΔS>0). The parameters of binding 5-fluorouracil by PAMAM G4-OH dendrimer were compared with those of binding this drug by the macromolecules of PAMAM G3-OH and G5-OH.

Study of the interactions of PAMAM G3-NH2 and G3-OH dendrimers with 5-fluorouracil in aqueous solutions.

The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate spontaneous (ΔG<0) bonding of 5-fluorouracil by both cationic PAMAM G3-NH2 dendrimer and hydroxyl PAMAM G3-OH dendrimer in aqueous solutions. PAMAM G3-NH2 dendrimer bonds about n= 25±8 drug molecules. Some of them n1= 5±1 are bonded by terminal amine groups with equilibrium constant K1= 3890±930, while the remaining ones n2= 24 ±3 are bonded by amide groups with equilibrium constant K2= 110±30. Hydroxyl PAMAM G3-OH dendrimer bonds n=6.0±1.6 molecules of 5-fluorouracil through tertiary amine groups with equilibrium constant K= 65±10. The parameters of bonding 5-fluorouracil by PAMAM G3-NH2 and G3-OH dendrimer were compared with those of bonding this drug by the macromolecules of PAMAM of generations G4-NH2, G5-NH2 and G5-OH.

Reactivity of aminophosphonic acids. Oxidative dephosphonylation of 1-aminoalkylphosphonic acids by aqueous halogens.

The reactions of 1-aminoalkylphosphonic acids with bromine-water, chlorine-water and iodine-water were investigated. The formation of phosphoric(v) acid, as a result of a halogen-promoted cleavage of the Cα-P bond, accompanied by nitrogen release, was observed. The dephosphonylation of 1-aminoalkylphosphonic acids was found to occur quantitatively. In the reactions of 1-aminoalkylphosphonic acids with other halogen-water reagents investigated by (31)P NMR, scission of the Cα-P bond was also observed, the reaction rates being comparable for bromine and chlorine, but much slower for iodine.

Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous solution.

The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate exothermic (ΔH<0) and spontaneous (ΔG < 0) combination of an antitumor drug, 5-fluorouracil, by both cationic PAMAM G5-NH2 dendrimer and its hydroxyl analog PAMAM G5-OH in aqueous solutions at room temperature. PAMAM G5-NH2 dendrimer combines about 70 molecules of the drug with equilibrium constant K ≅ 300, which is accompanied by an increase in the system order (ΔS < 0). Hydroxyl dendrimer, PAMAM G5-OH, combines about 14 molecules of 5-fluorouracil with equilibrium constant K ≅ 100. This process is accompanied by an increase in the system disorder (ΔS > 0).

Formation of complexes between PAMAM-NH2 G4 dendrimer and L-α-tryptophan and L-α-tyrosine in water.

Interactions between electromagnetic radiation and the side substituents of aromatic amino acids are widely used in the biochemical studies on proteins and their interactions with ligand molecules. That is why the aim of our study was to characterize the formation of complexes between PAMAM-NH2 G4 dendrimer and L-α-tryptophan and L-α-tyrosine in water. The number of L-α-tryptophan and L-α-tyrosine molecules attached to the macromolecule of PAMAM-NH2 G4 dendrimer and the formation constants of the supramolecular complexes formed have been determined. The macromolecule of PAMAM-NH2 G4 can reversibly attach about 25 L-α-tryptophan molecules with equilibrium constant K equal to 130±30 and 24±6 L-α-tyrosine molecules. This characterization was deduced on the basis of the solubility measurements of the amino acids in aqueous dendrimer solutions, the (1)H NMR and 2D-NOESY measurements of the dendrimer solutions with the amino acids, the equilibrium dialysis and the circular dichroism measurements of the dendrimer aqueous solutions with L-α-tryptophan. Our date confirmed the interactions of L-α-tryptophan and L-α-tyrosine with the dendrimer in aqueous solution and indicated a reversible character of the formed complexes.

Thermochemical and spectroscopic studies on the supramolecular complex of PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution.

The equilibrium of the formation of polyamidoamine dendrimer (PAMAM-NH(2) G4) and an oncological drug, 5-fluorouracil (FU) in water at room temperature has been examined. Using calorimetric titration, the number of active sites in the dendrimer combining the drug molecules and the equilibrium constant of the dendrimer-drug complex were estimated. The addition of the drug to the dendrimer active sites is an exothermic process. This process is accompanied by a beneficial change in entropy. The number of drug molecules combined by the polymer was confirmed by means of (1)H NMR spectroscopy. (1)HNMR measurements show that the dendrimer macromolecule binds the drug molecules with superficial protonated or unprotonated amine groups.

Interaction between PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution.

The formation equilibrium of poly(amidoamine) dendrimer (PAMAM-NH2 G4) complex with an oncologic drug such as 5-fluorouracil (5-FU) in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions and the method of equilibrium dialysis, the maximal number of drug molecules in the dendrimer-drug complex and its equilibrium constant were evaluated. Solubility results show that PAMAM-NH2 G4 dendrimer can transfer tens 5-fluorouracil molecules in aqueous solution. The number of active sites in a dendrimer macromolecule being capable of combining the drug, determined by the separation method, amounts to n=30 ± 4. The calculated equilibrium constant of the 5-FU-active site bonding is equal to K=(400 ± 120).