Biocoordination reactions in copper(II) ions and phosphocholine systems including pyrimidine nucleosides and nucleotides.

The complexation reactions of phosphocholine and pyrimidine nucleosides as well as nucleotides with copper(II) ions were studied in the water system. Using potentiometric methods and computer calculations, the stability constants of the species were determined. Using spectroscopic methods such as UV-vis, EPR, 13C NMR, 31P NMR, FT-IR and CD, the coordination mode was established for complexes created in pH range 2.5-11.0. These studies will lead to a better understanding the role of copper(II) ions in living organisms and explain the interactions between them and the studied bioligands. The differences and similarities between nucleosides and nucleotides in the studied systems were also described, which testify to the significant influence of phosphate groups on the processes of metal ion complexation and interactions between ligands.

Coordination Chemistry of Phosphate Groups in Systems Including Copper(II) Ions, Phosphoethanolamine and Pyrimidine Nucleotides.

The activity of phosphate groups of phosphoethanolamine and pyrimidine nucleotides (thymidine 5-monophosphate, cytidine 5-monophosphate and uridine 5'monophosphate) in the process of complexation metal ions in aqueous solution was studied. Using the potentiometric method with computer calculation of the data and spectroscopic methods such as UV-Vis, EPR, 13C and 31P NMR as well as FT-IR, the overall stability constants of the complexes as well as coordination modes were obtained. At lower pH, copper(II) ions are complexed only by phosphate groups, whereas the endocyclic nitrogen atom of nucleotides has been identified as a negative center interacting with the -NH3+ groups of phosphoethanolamine.

Influence of d-Electron Divalent Metal Ions in Complex Formation with L-Tartaric and L-Malic Acids.

Binary complexes of α-hydroxy acids (L-Tartaric acid and L-Malic acid) with d-electron metal ions (copper, cobalt, nickel) were investigated. Potentiometric measurements have been performed in aqueous solution with computer analysis of the data for determination of the stability constants of complexes formed in the studied systems. The coordination mode of the complexes was defined using spectroscopic methods: electron paramagnetic resonance (EPR), ultraviolet-visible (UV-Vis), circular dichroism (CD), and infrared (IR). Results of the equilibrium studies have provided evidence for the formation of dimers with copper(II) ions and monomers with cobalt(II) and nickel(II) ions.

The Influence of pH on Complexation Process of Copper(II) Phosphoethanolamine to Pyrimidine Nucleosides.

The influence of pH on the complex formation of phosphoethanolamine and pyrimidine nucleosides (uridine, cytidine and thymidine) with copper(II) ions was studied. All investigations were performed in aqueous solution. The overall stability constants of the complexes and non-covalent compounds were obtained using the potentiometric method with computer calculation of the data. Moreover, equilibrium constants of the reaction were determined. The mode of coordination was obtained using spectroscopic methods. Analysis of the potentiometric and spectroscopic data confirmed the involvement and effectiveness of phosphate groups in species formation as well as the influence of pH on the mode of coordination of the investigated biomaterials. In the next step, studied complexes will be applied as potential biomaterials with biological applications.

The Comparison of In Vitro Photosensitizing Efficacy of Curcumin-Loaded Liposomes Following Photodynamic Therapy on Melanoma MUG-Mel2, Squamous Cell Carcinoma SCC-25, and Normal Keratinocyte HaCaT Cells.

The research focused on the investigation of curcumin encapsulated in hydrogenated soy phosphatidylcholine liposomes and its increased photoactive properties in photodynamic therapy (PDT). The goal of this study was two-fold: to emphasize the role of a natural photoactive plant-based derivative in the liposomal formulation as an easily bioavailable, alternative photosensitizer (PS) for the use in PDT of skin malignancies. Furthermore, the goal includes to prove the decreased cytotoxicity of phototoxic agents loaded in liposomes toward normal skin cells. Research was conducted on melanoma (MugMel2), squamous cell carcinoma (SCC-25), and normal human keratinocytes (HaCaT) cell lines. The assessment of viability with MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) evaluated cell death after exposure to blue light irradiation after 4 h of pre-incubation with free and encapsulated curcumin. Additionally, the wound healing assay, flow cytometry, and immunocytochemistry to detect apoptosis were performed. The malignant cells revealed increased phototoxicity after the therapy in comparison to normal cells. Moreover, liposome curcumin-based photodynamic therapy showed an increased ratio of apoptotic and necrotic cells. The study also demonstrated that nanocurcumin significantly decreased malignant cell motility following PDT treatment. Acquired results suggest that liposomal formulation of a poor soluble natural compound may improve photosensitizing properties of curcumin-mediated PDT treatment in skin cancers and reduce toxicity in normal keratinocytes.

The Effect of a New Glucose-Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma Cell Lines.

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite-methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients' life. Therefore, novel targeted therapies based on the malignant cells' common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose-methotrexate conjugate (Glu-MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu-MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu-MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients' outcomes.

Expression of syndecan-1 in oral cavity squamous cell carcinoma.

Syndecan-1 (SDC1) belongs to heparan sulfate proteoglycans which may interact with different growth factors, cytokines, morphogens and promote tumor growth and invasion. The aim of the present study was to assess the immunohistochemical expression of syndecan-1 in oral squamous cell carcinoma (OSCC) and oral cysts. Evaluation of the staining pattern with the clinico-histological characteristics of patients was performed. A total of 42 OSCC and 23 oral cysts tissue samples were examined. Statistical tests were used for the significance analysis. The positive expression of syndecan-1 was significantly higher in OSCC compared to cyst located in the oral cavity. Moreover, the results indicate that the intensity of the expression correlated with grading score (p = 0.046). The data indicate that syndecan-1 is altered in OSCC and its excessive amount relates in a predictive manner to neoplastic transformation. As such, SDC1 expression may be used as an adjunctive biomarker in molecular diagnostics of oral squamous cell carcinoma.

The Effect of pH on the Size of Silver Nanoparticles Obtained in the Reduction Reaction with Citric and Malic Acids.

In colloidal methods, the morphology of nanoparticles (size and shape) as well as their stability can be controlled by changing the concentration of the substrate, stabilizer, adding inorganic salts, changing the reducer/substrate molar ratio, and changing the pH and reaction time. The synthesis of silver nanoparticles was carried out according to the modified Lee and Meisel method in a wide pH range (from 2.0 to 11.0) using citric acid and malic acid, without adding any additives or stabilizers. Keeping the same reaction conditions as the concentration of acid and silver ions, temperature, and heating time, it was possible to determine the relationship between the reaction pH, the type of acid, and the size of the silver nanoparticles formed. Obtained colloids were analyzed by UV-Vis spectroscopy and investigated by means of Transmission Electron Microscope (TEM). The study showed that the colloids reduced with citric acid and malic acid are stable over time for a minimum of seven weeks. We observed that reactions occurred for citric acid from pH 6.0 to 11.0 and for malic acid from pH 7.0 to 11.0. The average size of the quasi-spherical nanoparticles changed with pH due to the increase of reaction rate.

Thermodynamic and Spectroscopic Studies of the Complexes Formed in Tartaric Acid and Lanthanide(III) Ions Binary Systems.

Binary complexes of tartaric acid with lanthanide(III) ions were investigated. The studies have been performed in aqueous solution using the potentiometric method with computer analysis of the data for detection of the complexes set, determination of the stability constants of these compounds. The mode of the coordination of complexes found was determined using spectroscopy, which shows: Infrared, circular dichroism, ultraviolet, visible as well as luminescence spectroscopy. The overall stability constants of the complexes as well as the equilibrium constants of the reaction were determined. Analysis of the equilibrium constants of the reactions and spectroscopic data allowed the effectiveness of the carboxyl groups in the process of complex formation.

New coordination compounds of citric acid and polyamines with lanthanide ions - potential application in monitoring the treatment of cancer diseases.

Non-covalent interaction in the binary systems of polyamines (putrescine, spermidine, spermine) with citric acid and complex formation in the binary as well as ternary systems of lanthanide(III) ions, citric acid and polyamine have been investigated. The studies were performed in aqueous solution. The overall stability constants of the complexes were determined using the potentiometric method with computer analysis of the data. Only mononuclear type of complexes were found in the ternary systems and polyamines were located in the outer as well as inner coordination sphere. Non-covalent interaction between biogenic amines and citric acid in the binary and ternary systems were confirmed on the basis of the equilibrium constants analysis and spectroscopic studies.

Carboxyl groups of citric acid in the process of complex formation with bivalent and trivalent metal ions in biological systems.

Binary complexes of citric acid (H3L - protonated form, H2L and HL - partly protonated forms, L - fully deprotonated) with d- and f-electron metal ions were investigated. The studies have been performed in aqueous solution using the potentiometric method with computer analysis of the data, electron paramagnetic resonance, infrared, visible as well as luminescence spectroscopies. The overall stability constants of the complexes were determined. Analysis of the equilibrium constants of the reactions and spectroscopic data has allowed determination of the type of coordination and effectiveness of the carboxyl groups in the process of complex formation. On the basis of potentiometric titration for d-electron were found dimeric and monomeric type of complexes and for f-electron four type of complexes: MHL, ML, ML(OH) and ML(OH)2.

Concentration and Fractionation of Polyphenols by Membrane Operations.

BACKGROUND: This review aims to present the relevant background information and current research status in concentration of polyphenols using membrane technologies. The potential implementation of membrane separation to bioactive compounds like soluble phenolics from aqueous and organic solvent solutions is gaining increasing interest in the recent years. This review does not pretend to cover the abundant published literature on the subject, but to be representative for the observed tendencies in membrane processes applications for concentration of polyphenols derived from natural products. The first part of the article includes general information regarding the polyphenols and the traditional methods for their separation (such as: thin layer chromatography; paper chromatography; gas chromatography; high performance liquid chromatography; capillary electrophoresis), while the second part presents a review of different membrane processes applied for concentration of polyphenols. Three main sources for such implementations are discussed: (1) aqueous or organic solvent extracts from plant material, (2) fruits, and (3) recovery of polyphenols from industrial waste liquids. A diversity of membrane processes are considered in a large scope of implementations ranging from lab-scale studies to pilot and semiindustrial scale operations. CONCLUSION: Membrane technology is an excellent candidate to make a paradigm shift in biological active compounds fractionation/separation processes. Presented results clearly demonstrate that membrane processes are of great advantages over traditionally used methods; however, characterization of separated polyphenols has to be improved. Most of citied authors concentrated their investigation only on the total amount of polyphenols determination. Exhaustive studies including: antioxidant activities, retention index, total soluble solids, or volume reduction factor, have been only carried out by a few authors.