Preliminary studies on the mechanism of antifungal activity of new cationic β-glucan derivatives obtained from oats and barley

[Image: see text] New chemical structures with antifungal properties are highly desirable from the point of view of modern pharmaceutical science, especially due to the increasingly widespread instances of drug resistance in the case of these diseases. One way to solve this problem is to use polymeric drugs, widely described as biocidal, positively charged macromolecules. In this work, we present the synthesis of new cationic β-glucan derivatives that show selective antifungal activity and at the same time low toxicity toward animal and human cells. Two β-glucans isolated from oats and barley and modified using glycidyltrimethylammonium chloride were obtained and evaluated for biocidal properties on the cells of mammals and pathogenic fungi and bacteria. These compounds were found to be nontoxic to fibroblast and bacterial cells but showed selective toxicity to certain species of filamentous fungi (Scopulariopsis brevicaulis) and yeasts (Cryptococcus neoformans). The most important aspect of this work is the attempt to explain the mechanisms of action of these compounds by studying their interaction with biological membranes. This was achieved by examining the interactions with model biological membranes representative of given families of microorganisms using Langmuir monolayers. The data obtained partly show correlations between the results for model systems and biological experiments and allow indicating that the selective antifungal activity of cationic β-glucans is related to their interaction with fungal biological membranes and partly lack of such interaction toward cells of other organisms. In addition, the obtained macromolecules were characterized by spectral methods (Fourier transform infrared (FTIR) and (1)H nuclear magnetic resonance (NMR) spectroscopies) to confirm that the desired structure was obtained, and their degree of modification and molecular weights were determined

Young adults’ job satisfaction in Poland and the Czech Republic: a comparative analysis

Motivation: Job satisfaction as an attitude that reflects an evaluation judgment of the various aspects of a job is an essential factor influencing employees as well as employers. The well-being of individuals, activity in the labor market, productivity, and turnover are examples of effects of job satisfaction. The inclusion of the circumstances of Poland and the Czech Republic countries and additionally young generations (GenY and GenZ) context enables the formulation of practical implications for increasing job satisfaction for both employers and employees in CEE countries.Aim: The research aims to identify factors that shape job satisfaction patterns among young adults, including age as an indicator variable in Poland and the Czech Republic. The identification is based on the two separate ordered logit models estimated in the group of young adults ages 18–29. The models were built upon the data collected in 2021 in a survey using the CAWI technique on a sample of 304 respondents in Poland and 259 in the Czech Republic.Result: The results of the logit models estimation indicate that job satisfaction in Poland and the Czech Republic is determined by various sets of factors considered in four dimensions, i.e., behavioral, economic, educational, and socio-demographic. Substantial differences between young adults in both countries were recognized. The greatest impact on job satisfaction in Poland has the willingness to control expenses and wage satisfaction. In the Czech Republic, job satisfaction is most strongly influenced by the imposition of rules that discipline expenditure and wage satisfaction

The use of a barley-based well to define cationic betaglucan to study mammalian cell toxicity associated with interactions with biological structures

Among potential macromolecule-based pharmaceuticals, polycations seem particularly interesting due to their proven antimicrobial properties and use as vectors in gene therapy. This makes an understanding of the mechanisms of these molecules’ interaction with living structures important, so the goal of this paper was to propose and carry out experiments that will allow us to characterize these phenomena. Of particular importance is the question of toxicity of such structures to mammalian cells and, in the work presented here, two lines, normal fibroblasts 3T3-L1 and A549 lung cancer, were used to determine this. In this work, three well-defined cationic derivatives of barley-derived betaglucans obtained in a reaction with glycidyltrimethylammonium chloride (BBGGTMAC) with different degrees of cationization (50, 70, and 100% per one glucose unit) and electrostatic charge were studied. The studies address interactions of these polymers with proteins (bovine serum proteins and BSA), nucleic acids (DNA), glycosaminoglycans (heparin), and biological membranes. The results described in this study make it possible to indicate that toxicity is most strongly influenced by interactions with biological membranes and is closely related to the electrostatic charge of the macromolecule. The presentation of this observation was the goal of this publication. This paper also shows, using fluorescently labeled variants of polymers, the penetration and impact on cell structure (only for the polymer with the highest substitution binding to cell membranes is observed) by using confocal and SEM (for the polymer with the highest degree of substitution, and the appearance of additional structures on the surface of the cell membrane is observed). The labeled polymers are also tools used together with dynamic light scattering and calorimetric titration to study their interaction with other biopolymers. As for the interactions with biological membranes, lipid Langmuir monolayers as model membrane systems were used

Novel photosensitizers active in visible and near infrared spectral regions : synthesis and properties

Przedstawiona rozprawa doktorska koncentruje się na syntezie i określeniu właściwości fizykochemicznych halogenowanych kompleksów boru, z grupy subftalocyjanin oraz aza-BODIPY. Subftalocyjaniny (SubPc) są niższymi homologami ftalocyjanin (Pc), których strukturę aromatyczną buduje 14 zdelokalizowanych elektronów π. Chlor występujący w pozycji aksjalnej, łatwo ulega substytucji w reakcjach z nukleofilami, co pozwala na selektywne otrzymanie mono-modyfikowanej pochodnej. W ramach przedstawionej rozprawy, zaprojektowano syntezę chlorku heksajodo subftalocyjaniny boru (III) oraz jej modyfikacji na atomie boru. Substytucja atomu chloru w pozycji aksjalnej w reakcji z 3-hydroksypirydyną, a następnie uczwartorzędowienie obecnego w cząsteczce pirydyny atomu azotu, pozwoliła na otrzymanie kolejnych dwóch fotouczulaczy, o potencjalnie lepszych parametrach do zastosowań w fotomedycynie. W ostatnich dekadach bardzo duże zainteresowanie naukowców, wzbudziła nowa klasa związków, tj. aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenów (aza-BODIPY), które są pochodnymi lepiej poznanych 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenów (BODIPY). Zaplanowano więc syntezę polibromowanych barwników z grupy aza-BODIPY, zawierających w swojej strukturze podstawniki p-dimetyloaminofenylowe lub m-dimetyloaminofenylowe oraz p-tert-butylo-fenylowe. Wprowadzenie elektrodonorowych ugrupowań dimetyloaminowych (–NMe2) miało na celu przesunięcie widma absorpcji i emisji aza-BODIPY do zakresu bliskiej podczerwieni (NIR). Celem zwiększenia rozpuszczalności i ułatwienia izolacji oraz oczyszczania syntetyzowanych związków, do ich struktury wprowadzono ponadto duże objętościowo grupy tert-butylowe. Zaprojektowano i otrzymano barwniki posiadające w swoich strukturach ciężkie atomu bromu lub jodu celem zwiększenia populacji wzbudzonych stanów trypletowych, a tym samym zwiększenia wydajności kwantowej tworzenia tlenu singletowego (ΦΔ). Wszystkie badane związki charakteryzują się silną absorpcją w zakresie widzialnym lub bliskiej podczerwieni oraz niską wydajnością kwantową fluorescencji (SubPc, aza-BODIPY z podstawnikami p-dimetyloamino-fenylowymi). Aza-BODIPY z podstawnikami m-dimetyloaminofenylowymi nie wykazywały emisji w temperaturze pokojowej, ale zmierzono ich widma fluorescencji w szkliwie uzyskanym w niskiej temperaturze (T = 77 K). Na podstawie zarejestrowanych widm fluorescencji wyznaczono energie wzbudzonego stanu singletowego (ES). Ponadto dla subftalocyjanin zarejestrowano widma fosforescencji oraz wyznaczono energię wzbudzonego stanu trypletowego (ET). Zastosowanie techniki czasowo-rozdzielczej spektroskopii laserowej umożliwiło zbadanie dynamiki wzbudzonych stanów singletowych (S1) i trypletowych (T1) oraz wyznaczenie ich czasów życia (τS, τT). Przeprowadzone eksperymenty elektrochemiczne pozwoliły na wyznaczenie potencjałów procesów: pierwszego utlenienia (Eox1) i pierwszej redukcji (Ered1) oraz obliczenie energii orbitali granicznych HOMO (EHOMO) i LUMO (ELUMO) jak również elektrochemicznej przerwy energetycznej (Eg). Zwieńczeniem badań było przeprowadzenie pomiarów wydajności kwantowych tworzenia tlenu singletowego (ΦΔ). Najwyższą wartość ΦΔ otrzymano dla chlorku heksajodo-subftalocyjaniny boru, ΦΔ = 0.90. Przeprowadzone eksperymenty dla aza-BODIPY z grupami –NMe2 wykazały, że dzięki obecności tych grup funkcyjnych, otrzymane barwniki są wrażliwe na pH roztworu, w którym się znajdują. Objawia się to hipsochromowym przesunięciem maksimum absorpcji oraz pojawieniem się silnej fluorescencji diprotonowanej (obie grupy -NMe2) formy barwnika. W świetle przedstawionych w pracy wyników, można wnioskować, że otrzymane barwniki wykazują duży potencjał jako nowe materiały dla wielu zastosowań praktycznych, między innymi jako: fotokatalizatory, warstwy fotoaktywne w ogniwach słonecznych (DSSC), organiczne diody elektroluminescencyjne (OLED), fotouczulacze w terapii i diagnostyce fotodynamicznej (PDT i PDD).The research presented in the doctoral thesis concentrated on the synthesis and determination of physicochemical properties of halogenated boron complexes, such as subphthalocyanine and aza-BODIPY. Subphthalocyanines (SubPcs) are lower homologs of phthalocyanines, containing 14 π electron core. Chlorine atom in axial position can be easily displaced by certain nucleophiles that allow synthesis monosubstituent derivatives. Synthesis of boron (III) hexaiodosubphthalocyanine chloride and its modification at the boron atom was designed and executed. Substitution of the chlorine atom in the axial position by reaction with 3-hydroxypyridine, followed by quaternization of the nitrogen atom present in the pyridine molecule, allowed to obtain novel, interesting photosensitizers, potentially better suited for photomedicine applications. Recently, there is a growing interest in new class of compounds, i.e. aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (aza-BODIPY), which are derivatives of better-known 4.4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY). Therefore, synthesis of polybrominated aza-BODIPY with p-dimethylaminophenyl or m-dimethylaminophenyl substituents as well as p-tert-butylphenyl substituents was undertaken. Dimethylamino groups (-NMe2) of electrondonor nature were introduced to the structure of synthesized compounds to shift the absorption and emission spectrum into the near infrared (NIR) region. Tert-butyl groups were added to increase the solubility and to facilitate the isolation and purification of the photosensitizers prepared. The iodine or bromine atoms present in molecules of dyes were introduced to increase the population of excited triplet state (T1), which should result in high quantum yield of singlet oxygen and other ROS formation (ΦΔ) on quenching with molecular oxygen. The dyes synthesized are characterized by strong absorption in the visible or near infrared region and low quantum yield of fluorescence (SubPc, aza-BODIPY with p-dimethylaminophenyl substituents) or are non-emissive at room temperature (aza-BODIPY with m-dimethylaminophenyl substituents). Based on the recorded fluorescence spectra, the energies of the excited singlet state (ES) were determined. In addition, for subphthalocyanine the phosphorescence spectra were recorded and the energies of the excited triplet state (ET) were calculated. Furthermore, time-resolved measurements allowed observation of the dynamics of excited singlet (S1) and triplet states (T1) and determination of their lifetime (τS, τT). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to determine the first oxidation (Eox1) and the first reduction (Ered1) potentials as well as to calculate HOMO (EHOMO) and LUMO (ELUMO) energy levels and electrochemical energy gaps (Eg). Quantum yields of singlet oxygen generation (ΦΔ) were determined. The highest value of ΦΔ equal to 0.90 was obtained for boron (III) hexaiodosubphthalocyanine chloride. Due to the presence of -NMe2 groups aza-BODIPY are pH sensitive, as manifested by the hypsochromic shift of the absorption maximum and the appearance of strong fluorescence from the diprotonated (both -NMe2) dye forms. Based on the results presented in thesis, one can conclude that the obtained dyes have a great potential as new photoactive materials for various applications, such as: photocatalysts, photoactive layers in solar cells (DSSC), organic electroluminescent diodes (OLED), photosensitizers for photodynamic therapy (PDT and aPDT) and sensors

Synthesis and physicochemical properties of novel fluorinated phthalocyanines

Przedmiotem badań przedstawionej pracy dyplomowej było otrzymanie, charakterystyka spektroskopowa, fotofizyczna, spektro/elektrochemiczna wybranych perfluorowanych ftalocyjanin indu (III) 12, galu (III) 13 oraz glinu (III) 14. Wymienione ftalocyjaniny zostały otrzymane w reakcji perfluoro-(4,5-diizopropylo)ftalonitrylu 2 z trójchlorkiem indu, galu i glinu. Uzyskano bardzo dobre wydajności reakcji (ok. 50 %). Ponadto, podjęto próby syntezy niesymetrycznej ftalocyjaniny cynku. W pracy opisano syntezę prekursora do otrzymania wspomnianej ftalocyjaniny, tj. kwasu 4,5-dicyjano-2-metylo-benzoesowego (9). Wszystkie otrzymane związki zostały scharakteryzowane przy użyciu metod spektroskopowych (MALDI-MS, ESI-MS, FT-IR, NMR, UV-Vis, 19F NMR, 13C NMR, 1H NMR) oraz analizy elementarnej. Przeprowadzone badania potencjałów redoks wykazały podatność otrzymanych barwników na redukcję i całkowitą odporność na procesy utleniania w badanych zakresach potencjałów. Ponadto, otrzymane ftalocyjaniny indu 12, galu 13 oraz glinu 14 charakteryzują się bardzo wysokimi molowymi współczynnikami absorpcji (powyżej 200 000 M-1cm-1), silną absorpcją w zakresie widzialnym widma UV-Vis, oraz fluorescencją silnie uzależnioną od metalu obecnego we wnęce ftalocyjaniny. Badając zależność absorbancji od stężenia stwierdzono, że obecność grup perfluoro-izo-propylowych skutecznie zapobiega procesom agregacji badanych ftalocyjanin w roztworach. Badane ftalocyjaniny charakteryzują się bardzo wysoką trwałością termiczną co potwierdzono wykonując analizę termograwimetryczną (TGA).The main objective of this study was to obtain and characterize three perfluoro-phthalocyanines with indium, gallium and aluminum incorporated in the phthalocyanine macrocycle. These phthalocyanines were obtained by reacting perfluoro-(4,5-di-iso-propyl)phthalonitrile with the corresponding indium, gallium or aluminum chlorides. Attempts to synthesize the unsymmetrical zinc phthalocyanine were made. The synthesis and characterization of 4,5-dicyanine-2-methyl benzenoic acid, as the precursors for phthalocyanine under discussion was described. The redox properties of perfluorinated materials were examined by cyclic voltammetry (CV) indicating complete resistance of these materials to oxidation and susceptibility to reduction (n-type material). The spectroelectrochemical analysis indicates that the redox processes observed are ring-centered. Thermogravimetric analysis points to exceptional thermal stability of indium, gallium and aluminum perfluoro-phthalocyanines. Presence of bulky perfluoro-iso-propyl groups prevents aggregation of these dyes both in solution and in solid. Fluorescence quantum yields of indium, gallium and aluminum phthalocyanines strongly depends on the metal incorporated into the phthalocyanine macrocycle