Acanthamoebae are opportunistic pathogens causing serious human infections, including granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The treatment of those infections is limited and difficult to date. Recent research demonstrated high antimicrobial activity of phosphonium amphiphilic salts. In the present work we aimed to investigate the anti-Acanthamoeba effect of a series of 16 phosphonium salts. The structure of these synthesized cationic amphiphiles was modified in both the polar and nonpolar parts of the surfactant molecule. The compounds have different alkyl chain lengths (C12 - C18) and different numbers of methyl and phenyl groups (0 - 3) attached to the quaternary phosphorus atom. The following basic physicochemical properties of the compounds were determined: critical micelle concentration (cmc), the surface tension value at the cmc and the surface area per surfactant head group. The cmc values, which express the degree of lipophilicity of compounds, were correlated with biological activities. The effects of phosphonium salts on trophozoites of Acanthamoeba quina and Acanthamoeba hatchetti (both strains of genotype T4) and human erythrocytes were studied. The highest trophocidal activity was recorded for the compound C16P(Me)2PhBr with the minimal trophocidal concentration (MTC) of 7.8 μM for the A. quina strain and 15.6 μM for the A. hatchetti strain, after 24 h. Its activity was comparable or higher than the activity of drugs currently used in the treatment of Acanthamoeba keratitis. Therefore, this compound is a promising candidate in the fight against infections caused by Acanthamoeba.

Since the last decade, silver nanoparticles (AgNPs) continue to attract interest of both academia and industry due to their peculiar physical, chemical, and optical properties. In the field of pharmaceutical applications, they are efficient carriers in the processes of controlled drug release, improve the drug’s bioavailability, act as efficient antimicrobial agents and provide other biological functions conveyed at the nanometric scale. The known issue hampering further development of applications of AgNPs is their instability in aqueous environment. The present study utilizes two series of cationic bisammonium gemini surfactants with two dodecyl chains and a biodegradable spacer containing two amide or ester groups for the stabilization of AgNPs. The presence of nanosilver in the dispersions was confirmed by UV-VIS plasmon resonance spectra. Stability of AgNPs was characterized by zeta potential measurements proving that amide and ester gemini surfactant series are able to effectively stabilize AgNPs. The particles size analysis utilizing dynamic light scattering and scanning electron microscopy showed that AgNPs stabilized with flexible ester-based gemini surfactants have their size smaller than those capped with amide-containing gemini surfactants. Antimicrobial and anti-inflammatory activity determination as well as cytotoxicity experiments with gemini surfactant stabilized AgNPs showed a complex dependence of biological activity of AgNPs on the molecular structure of stabilizing agents.

Synthesis, aggregation parameters and antimicrobial activity of novel cationic gemini surfactants with two amide groups in gemini spacer structure and a variable number of carbon atoms in alkyl tails ranging from 12 to 15 are reported. The critical micelle concentration of gemini surfactants was determined using surface tension and electrical conductivity methods. The cmc values were found in the range 0.83 to 0.06 mM. The interfacial area, micelle ionisation degree and the Gibbs free energy per molecule and alkyl chain were calculated from the surface tension and conductivity curves. Particle size analysis using the dynamic light scattering method confirmed the formation of small spherical micelles 6–7 nm large in size for gemini surfactants with 12 and 13 carbon atoms in the alkyl chain. A large size above 50 nm was found for the aggregates composed of long-chain gemini molecules with 14 and 15 carbon atoms. The zeta potential of gemini surfactants shows a continuous increase with the increasing alkyl chain length. Micelle aggregation number of gemini surfactants correlates well with the hydrodynamic size data. Small aggregation number values were found for short-chain gemini molecules with 12 and 13 carbon atoms in the alkyl chain. Long-chain gemini molecules with 14 and 15 carbon atoms exhibit aggregate growth represented by an increase in the aggregation number values while maintaining the spherical or spheroidal shape of micelles. The investigations of antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and yeast indicate the increasing antimicrobial efficiency towards the short-chain surfactant with 12 carbon atoms in the alkyl chain. A possible cut-off effect presence is proposed to explain the dependence of antimicrobial activity on the surfactant alkyl tail length.

Gold nanoparticles were prepared by the method of chemical reduction utilising sodium borohydride as reducing agent and stabilised with bisammonium gemini surfactants with variable length of poly-methylene spacer. Physico-chemical investigations indicated the presence of plasmon resonance peaks in the wavelength range 507-544 nm for all investigated Au nanodispersions. The nanoparticle size anal-ysis shows the relationship between the size of gold nanoparticles and the spacer length of stabilising gemini molecules. The strong aggregation tendency of gemini surfactants with short polymethylene spacer composed of 2-4 methylene units in aqueous solutions may be responsible for the formation of clusters of gold nanoparticles which results in the observed large hydrodynamic size of nanoparticle clus-ters at the surfactants concentrations below the CMC. At higher surfactant-to-gold molar ratio values, clusters disintegration occurs and the decrease in size of the nanoparticles is observed. The shape of gold nanoparticles was found to be spherical and polyhedral, as evidenced by the SEM images. The size values varied between 30-60 nm and 10-15 nm for AuNPs capped with gemini molecules with short and medium/long spacer, respectively. Gold nanoparticles are strongly positively charged, with positive zeta potential values being in the interval +44 to +90 mV in the whole analysed region of molar ratio values and surfactant spacer length. The biological experiments indicate a dependence of biological activity of gold nanoparticles on the structural parameter (spacer length) of stabilising gemini molecules. Both cyto-toxicity and anti-inflammatory activity of gold nanoparticles were found to increase with the increasing gemini spacer length up to 12 methylene groups in the spacer.(c) 2022 Elsevier B.V. All rights reserved.

The origin of life, based on the homochirality of biomolecules, is a persistent mystery. Did life begin by using both forms of chirality, and then one of the forms disappeared? Or did the choice of homochirality precede the formation of biomolecules that could ensure replication and information transfer? Is the natural choice of L-amino acids and D-sugars on which life is based deterministic or random? Is the handedness present in/of the Universe from its beginning? The whole biosystem on the Earth, all living creatures are chiral. Many theories try to explain the origin of life and chirality on the Earth: e.g., the panspermia hypothesis, the primordial soup hypothesis, theory of parity violation in weak interactions. Additionally, heavy neutrinos and the impact of the fact that only left-handed particles decay, and even dark matter, all have to be considered.

Phosphorus-containing heterocyclic cationic surfactants alkyldimethylphenylphospholium bromides with the alkyl chain length 14 to 18 carbon atoms were used for the stabilization of silver nanodispersions. Zeta potential of silver nanodispersions ranges from +35 to +70 mV, which indicates the formation of stable silver nanoparticles (AgNPs). Long-chain heptadecyl and octadecyl homologs of the surfactants series provided the most intensive stabilizing effect to AgNPs, resulting in high positive zeta potential values and smaller diameter of AgNPs in the range 50–60 nm. A comparison with non-heterocyclic alkyltrimethylphosphonium surfactants of the same alkyl chain length showed better stability and more positive zeta potential values for silver nanodispersions stabilized with heterocyclic phospholium surfactants. Investigations of biological activity of phospholium-capped AgNPs are represented by the studies of antimicrobial activity and cytotoxicity. While cytotoxicity results revealed an increased level of HepG2 cell growth inhibition as compared with the cytotoxicity level of silver-free surfactant solutions, no enhanced antimicrobial action of phospholium-capped AgNPs against microbial pathogens was observed. The comparison of cytotoxicity of AgNPs stabilized with various non-heterocyclic ammonium and phosphonium surfactants shows that AgNPs capped with heterocyclic alkyldimethylphenylphospholium and non-heterocyclic triphenyl-substituted phosphonium surfactants have the highest cytotoxicity among silver nanodispersions stabilized by the series of ammonium and phosphonium surfactants.

A series of alkylphosphocholines with foscarnet moiety was synthesized. The structure of these zwitterionic amphiphiles was modified in both polar and non-polar parts of surfactant molecule. Investigations of physicochemical properties are represented by the determination of critical micelle concentration, the surface tension value at the cmc and the surface area per surfactant head group utilising surface tension measurements. Hydrodynamic diameter of surfactant micelles was determined using the dynamic light scattering technique. Alkylphosphocholines exhibit significant cytotoxic, anticandidal (Candida albicans) and antiamoebal (Acanthamoeba spp. T4 genotype) activity. The relationship between the structure, physicochemical properties and biological activity of the tested compounds revealed that lipophilicity has a significant influence on biological activity of the investigated surfactants. More lipophilic alkylphosphocholines with octadecyl chains show cytotoxic activity against cancer cells which is higher than that of the compounds with shorter alkyl chains. The opposite situation was observed in case of anticandidal and antiamoebal activity of these surfactants. The most active compounds were found to have pentadecyl chains. The foscarnet analogue of miltefosine C15-PFA-C showed the highest anticandidal activity. The minimum value of anticandidal activity of this compound is 1,4 μM thus representing the highest anticandidal activity found within the group of alkylphosphocholines.

A series of phosphonium amphiphilic compounds was synthesized. Cationic parts of molecules contain triphenylphosphonium moieties. Lipophilic parts of compounds are represented by straight alkyl chain or the alkyl chains which are ornamented by benzyl or metronidazole. The physicochemical properties of phosphonium amphiphilic compounds were investigated by the measurements of surface tension and conductivity. The critical micelle concentration (cmc), the surface tension value at the cmc (gamma(cmc)), the surface area at the surface saturation per head group (A(cmc)) were determined. The lowest cmc value was determined for phosphonium salts with straight dodecyl alkyl chain. Its value was 1.5 x 10(-3)mol dm(-3). Surface tension at the cmc decreases with the addition of bulky moieties (benzyl, radical from metronidazol) at the end of alkyl chains. Biological activities of compounds were studied on human erythrocytes and strains ofAcanthamoeba lugdunensisandAcanthamoeba quina. Dodecyltriphenylphosphonium bromide showed the highest activity againstAcanthamoeba. To the best of our knowledge, it is the first compound of the group of phosphonium amphiphiles, which exhibited high activity againstAcanthamoeba. The determined structure-activity relationship indicated nonspecific trophocidal and hemolytic activity that depends on physicochemical properties of the studied compounds.

A series of nineteen novel ring-substituted N-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested against Staphylococcus aureus as the reference strain, two clinical isolates of methicillin-resistant S. aureus (MRSA), and Mycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 µM) against MRSA isolates than the commonly used ampicillin (MIC 45.8 µM). The screening of the cell viability was performed using THP1-Blue™ NF-κB cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC50 6.5 µM), none of the discussed compounds showed any significant cytotoxic effect up to 20 μM. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pKa calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.

pH-sensitive liposomes composed of homologues of series of N,N-dimethylalkane-1-amine N-oxides (CnNO, n = 8-18, where n is the number of carbon atoms in the alkyl substituent) and neutral phospholipid dioleoylphosphatidylethanolamine (DOPE) were prepared at two molar ratios (CnNO/DOPE = 0.4:1 and 1:1) and tested for their in vitro transfection activity. Several techniques (SAXS/WAXS, UV-vis, zeta potential measurements, confocal microscopy) were applied to characterize the system in an effort to unravel the relationship among the transfection efficiency, structure, and composition of the lipoplexes. The transfection efficiency of CnNO/DOPE for plasmid DNA in U2OS cells follows a quasi-parabolic dependence on CnNO's alkyl substituent length with a maximum at n = 16. The transfection efficiency of CnNO/DOPE (n = 12-18) lipoplexes was found to be higher than that of commercially available Lipofectamine 2000. C16NO/DOPE also positively transfected HEK 293T and HeLa cells. Small-angle X-ray scattering (SAXS) shows large structural diversity depending on the complex's composition and pH. Transfection efficiencies mediated by two structures, either a condensed lamellar (L-alpha(c)) or epitaxially connected L-alpha(c) and a condensed inverted hexagonal (H-II(c)) phase (L-alpha(c) & H-II(c)), were found to be very similar. The change in pH from acidic to neutral induces phase transition L-alpha(c) & H-II(c) -> Q(II) + L-alpha, with cubic phase Q(II) of the Pn3m space group. Q(II) detected in lipoplexes of most efficient composition CnNO/DOPE (n = 16 and 18) facilitates DNA release and promotes its internalization in the cell.

OBJECTIVES:To compare two different analytical methods for determination of small dense LDL and to determine a share of corresponding and non-corresponding (inconsistent) results METHODS: In the group of 104 hyperlipidemic patients and 20 healthy individuals of the control group we analysed the total cholesterol and triglycerides by enzymatic CHOD PAP method (Roche Diagnostics, Germany) in EDTA-K2 plasma. Small dense LDL (sdLDL) were quantified by the electrophoretic method for lipoprotein analysis on polyacrylamide gel (PAG) (Lipoprint LDL System, Quantimetrix, CA, USA) and simultaneously, the small dense LDL concentrations in the indentical samples were analysed by an enzymatic method LDL-EX ´Seiken´(Randox, England).RESULTS:In 31 patients we found the discrepancy in the sdLDL levels using the two different procedures. Out of them, 24 patients tested by enzymatic method ´SEIKEN´ had higher sdLDL values (more than 0.9 mmol/l) compared to the Lipoprint LDL results, which identified normal sdLDL values in the same samples (in 23% of tested patients). In 7 patients out of the 31 tested patients with discrepant sdLDL values, the Lipoprint LDL identified increased values of plasma sdLDL (more than 0.155 mmol/l), while the enzymatic LDL-EX Seiken did not find an increased concentration of sdLDL (in 7% of tested patients). In the control group a discrepancy in the sdLDL results between the two tested analytical methods was not found.CONCLUSION:The concentration of sdLDL in plasma lipoprotein spectrum obtained by two different laboratory procedures was analysed, compared, evaluated and 70% identical corresponding results have been confirmed.

Cationic gemini surfactants with polymethylene spacer and linear alkyl chains containing an even number of carbon atoms have been extensively studied in the recent past, with the emphasis put on the determination of their aggregation behaviour in aqueous solution and their biological properties. However, the information on the aggregation of branched gemini surfactants with an odd number of carbon atoms in their alkyl chains is only sparsely reported in the literature. To help cover this gap in the research of cationic gemini surfactants, a series of branched bisammonium cationic gemini surfactants with an odd number of carbon atoms in alkyl chains (tridecane-2-yl chains) and a polymethylene spacer with a variable length ranging from 3 to 12 carbon atoms have been synthesized and investigated. Critical micelle concentration, which was determined by three methods, was found to be in the order 10-4 mol/L. A comparison of the obtained data of the novel series of tridecyl chain geminis with those of gemini surfactants with dodecyl chains and an identical spacer structure revealed that structural differences between both series of gemini surfactants result in different aggregation and surface properties for surfactants with 6 and 8 methylene groups in the spacer (N,N'-bis(tridecane-2-yl)-N,N,N',N'-tetramethylhexane-1,6-diaminium dibromide and N,N'-bis(tridecane-2-yl)-N,N,N',N'-tetramethyloctane-1,8-diaminium dibromide) with the cmc values 8.2 × 10-4 mol/L and 6.5 × 10-4 mol/L, respectively, as determined by surface tension measurements. Particle size analysis showed the formation of small stable spherical micelles in the interval between 2.8 and 5 nm and with zeta potential around +50 mV, which are independent of surfactant concentration and increase with the increasing spacer length. Microbicidal activity of 13-s-13 gemini surfactants was found to be efficient against Gram-positive, Gram-negative bacteria and yeast.

: Self-assembly properties of cationic gemini surfactants with biodegradable amide or ester groups in the spacer were investigated utilising time-resolved fluorescence quenching, dynamic light scattering and zeta potential measurements. A correlation between aggregation parameters such as micelle aggregation number, micelle size and zeta potential with the structure of gemini molecules was made. For gemini molecules with medium spacer lengths, micelle aggregation number does not change much with the surfactant concentration. When the spacer is extended, a stronger aggregation tendency is observed for gemini surfactant molecules with two ester groups in the spacer and the aggregation number increases. The assumption of stronger aggregation of ester-based gemini molecules at larger spacer number values is also documented by measurements of the size and zeta potential of ester-based micelles. The explanation of the difference in aggregation ability of amide-based and ester-based gemini molecules is related to the structural features of gemini molecules, notably to the larger flexibility and denser arrangement of ester-based gemini molecules in a micelle. To support this assumption, optimised 3D models of the studied gemini molecules were constructed. Correspondingly, the calculations show smaller size and interfacial area for ester-based gemini conformers.

A series of six di- and tri-halogenated N-arylcinnamanilides designed as anti-inflammatory and antimicrobial agents was prepared and characterized. Since it is known that lipophilicity significantly influences the biological activity of compounds, the hydro-lipophilic properties of these di- and tri-substituted N-arylcinnamanilides were investigated in the study. All the discussed derivatives of cinnamic acid were analyzed using the reversed-phase high performance liquid chromatography method to measure lipophilicity. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In the present study, the correlations between the logarithm of the capacity factor k and log P/Clog P values calculated in various ways as well as the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.

A series of ring-substituted N-arylcinnamamides was prepared, characterized, and investigatedfor their antimicrobial efficacy in detail [...]

A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)- 3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 µM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C(2,5)ʹ or C(2,6)ʹ positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.

An improved method of isolation of betulin and lupeol from birch bark is developed and reported. The method afforded triterpenes with purity of 98.2% (betulin) and 96.3% (lupeol), respectively. Chromyl chloride was also investigated as an oxidating agent of O-acetylated betulin and lupeol. The transformation of isopropenyl moiety to aldehyde group was observed.

DNA condensation, structure and transfection efficiency of complexes formed by gemini surfactants alkane-α,ω-diyl-bis(dodecyldimethylammonium bromide)s (CnGS12, n = 3, 6 and 12 is the number of alkane spacer carbons), dioleoylphosphatidylethanolamine (CnGS12/DOPE = 0.3 mol/ mol) and DNA at low surface charge density were investigated through different techniques.Small angle X-ray diffraction showed a condensed lamellar phase with marked dependence of DNA-DNA distance on (+/-) charge ratio.High ionic strength of hydrating medium screens the interaction DNA -CnGS12/DOPE and complexed DNA represented maximally ~ 45-60% of total DNA in the solution as derived from fluorescence and UV-VIS spectroscopy.The in vitro transfection efficiency of CnGS12/DOPE liposomes on mammalian HEK 293 cell line was spacer length-dependent.C12GS12/DOPE/DNA complexes exhibited the best transfection efficiency (~ 18% GFP-expressing cells relative to all viable cells) accompanied by ~ 89% cell viability.

Silver nanoparticles were prepared by chemical reduction method and stabilised with cationic single-chain phosphonium surfactants of variable alkyl chain length and a different number of methyl and phenyl substituents in the hydrophilic headgroup part of surfactant molecule. Physical properties of silver nanoparticles were studied utilizing several experimental methods, such as visible spectroscopy, dynamic light scattering and scanning electron microscopy for the nanoparticle size determination and zeta potential measurements for the characterization of the charge of nanoparticles. As the physical measurements indicate, zeta potential of phosphonium surfactant stabilised silver nanodispersions was found to be in the range +27 mV to +50 mV depending on the alkyl chain length of the stabilising surfactant. Hydrodynamic diameter values of phosphonium surfactant stabilised silver nanoparticles were found to be between 40 nm and 109 nm with the smallest diameter values being around 40 nm for the nanoparticles stabilised with hydrophobic triphenyl-substituted phosphonium surfactants. Investigations of biological activity of both silver nanodispersions and silver-free aqueous solutions of surfactants are represented by the determination of antimicrobial activity against Gram-negative, Gram-positive bacterial strains and against yeast. Cytotoxicity of the systems mentioned above was determined on human carcinoma HepG2 cell line. Based on the obtained results, the relationship between phosphonium surfactant structure and physical and biological properties of nanoparticles is analysed. The results indicate that the increasing number of phenyl substituents in the surfactant headgroup and the increasing alkyl chain length play a dominant role in the improvement of biological activity of phosphonium surfactant stabilised silver nanoparticles as well as result in the formation of stable silver nanodispersions with small hydrodynamic diameter and a highly positive zeta potential. (C) 2020 Elsevier B.V. All rights reserved.

Urease plays a significant role in the pathogenesis of several diseases and also has practical implications in other fields, such as agriculture or chemical analysis. Among the multitude of chemical species known to inhibit urease, metal complexes stand out as a special category due to their specific mechanism of action, distinct from purely organic substances. Their inhibitory activity seems to depend on the type of metal and its oxidation state as well as on the coordination environment of the central atom. Furthermore, the study of the interaction between metal ions and their complexes with urease renders valuable insights into detailed catalytic mechanisms of this enzyme. This brief survey attempts to provide an overview of the published research on urease inhibition by metal complexes. [GRAPHICS] .