Search Results (11)

One of the most important steps in the synthesis of 1,4-dihydropyridine (1,4-DHP) amphiphiles is the bromination of methyl groups in positions 2 and 6 of the entire ring. However, up to now, only N-bromosuccinimide was mainly used for bromination 1,4-DHPs. In this work, the synthesis of bis-1,4-DHP derivatives with ethyl and dodecyl ester groups attached to 1,4-DHP ring at positions 3 and 5 was performed by Hantzsch synthesis. The experimental studies were carried out to find out the best conditions and the agent for the tetra bromination of bis-1,4-DHP methyl groups at positions 2 and 6. Four different brominating agents were screened. The use of pyridinium bromide–perbromide in ethyl acetate was found to be optimal for the bromination of methyl groups. The bromination reaction was followed by the synthesis of cationic pyridine moiety containing amphiphilic bis-1,4-DHP derivatives. By nucleophilic substitution of bromine with various substituted pyridines, 12 new amphiphilic bis-1,4-DHP derivatives were obtained. Evaluation of self-assembling properties of tetracationic bis-1,4-dihydropyridine derivatives by dynamic light scattering (DLS) measurements was also performed. Full article

Liposomes and other nanoparticles have been widely studied as innovative nanomaterials because of their unique properties. Pyridinium salts, on the basis of 1,4-dihydropyridine (1,4-DHP) core, have gained significant attention due to their self-assembling properties and DNA delivery activity. This study aimed to synthesize and characterize original N-benzyl substituted 1,4-dihydropyridines and evaluate the influence on structure modifications on compound physicochemical and self-assembling properties. Studies of monolayers composed of 1,4-DHP amphiphiles revealed that the mean molecular areas values were dependent on the compound structure. Therefore, the introduction of N-benzyl substituent to the 1,4-DHP ring enlarged the mean molecular area by almost half. All nanoparticle samples obtained by ethanol injection method possessed positive surface charge and average diameter of 395–2570 nm. The structure of the cationic head-group affects the size of the formed nanoparticles. The diameter of lipoplexes formed by 1,4-DHP amphiphiles and mRNA at nitrogen/phosphate (N/P) charge ratios of 1, 2, and 5 were in the range of 139–2959 nm and were related to the structure of compound and N/P charge ratio. The preliminary results indicated that more prospective combination are the lipoplexes formed by pyridinium moieties containing N-unsubstituted 1,4-DHP amphiphile 1 and pyridinium or substituted pyridinium moieties containing N-benzyl 1,4-DHP amphiphiles 5a–c at N/P charge ratio of 5, which would be good candidates for potential application in gene therapy. Full article

Quaternary ammonium salts (QAS) are irreplaceable membrane-active antimicrobial agents that have been widely used for nearly a century. Cetylpyridinium chloride (CPC) is one of the most potent QAS. However, recent data from the literature indicate that CPC activity against resistant bacterial strains is decreasing. The major QAS resistance pathway involves the QacR dimer, which regulates efflux pump expression. A plausible approach to address this issue is to structurally modify the CPC structure by adding other biologically active functional groups. Here, a series of QAS based on pyridine-4-aldoxime were synthesized, characterized, and tested for antimicrobial activity in vitro. Although we obtained several potent antiviral candidates, these candidates had lower antibacterial activity than CPC and were not toxic to human cell lines. We found that the addition of an oxime group to the pyridine backbone resulted in derivatives with large topological polar surfaces and with unfavorable cLog P values. Investigation of the antibacterial mode of action, involving the cell membrane, revealed altered cell morphologies in terms of corrugated and/or disrupted surface, while 87% of the cells studied exhibited a permeabilized membrane after 3 h of treatment at 4 × minimum inhibitory concentration (MIC). Molecular dynamic (MD) simulations of the interaction of QacR with a representative candidate showed rapid dimer disruption, whereas this was not observed for QacR and QacR bound to the structural analog CPC. This might explain the lower bioactivity of our compounds, as they are likely to cause premature expression of efflux pumps and thus activation of resistance. Full article

Quaternization and metathesis approaches were used to successfully design and synthesize the targeted dicationic bis-dipyridinium hydrazones carrying long alkyl side chain extending from C8 to C18 as countercation, and attracted to halide (I^-) or fluorinated ion (PF₆^-, BF₄^-, CF₃COO^-) as counteranion. Spectroscopic characterization using NMR and mass spectroscopy was used to establish the structures of the formed compounds. In addition, their thermal properties were investigated utilizing thermogravimetric analyses (TGA), and differential scanning calorimetry (DSC). The thermal study illustrated that regardless of the alkyl group length (Cn) or the attracted anions, the thermograms of the tested derivatives are composed of three stages. The mode of thermal decomposition demonstrates the important roles of both anion and alkyl chain length. Longer chain length results in greater van der Waals forces; meanwhile, with anions of low nucleophilicity, it could also decrease the intramolecular electrostatic interaction, which leads to an overall interaction decrease and lower thermal stability. The DFT theoretical calculations have been carried out to investigate the thermal stability in terms of the T_onset. The results revealed that the type of the counteranion and chain length had a substantial impact on thermal stability, which was presumably related to the degree of intermolecular interactions. However, the DFT results illustrated that there is no dominant parameter affecting the thermal stability, but rather a cumulative effect of many factors of different extents. Full article

Novel dicationic pyridinium ionic liquids tethering amphiphilic long alkyl side chains and fluorinated counter anions have been successfully synthesized by means of the quaternization of the dipyridinium hydrazone through its alkylation with different alkyl halides. The resulting halogenated di-ionic liquids underwent a metathesis reaction in order to incorporate some fluorinated counter anions in their structures. The structures of all the resulting di-ionic liquids were characterized by several spectroscopic experiments. The antitumorigenic activities of the investigated compounds were further studied against three different human lung cancer cell lines. Compared to the standard chemotherapeutic agent, cisplatin, the synthesized di-ionic liquids exerted equal, even more active, moderate, or weak anticancer activities against the various lung cancer cell lines under investigation. The observed anticancer activity appears to be enhanced by increasing the length of the aliphatic side chains. Moreover, dicationic pyridinium bearing a nine carbon chain as counter cation and hexafluoro phosphate and/or tetrafluoro bororate as counter anion were selected for further evaluation and demonstrated effective and significant antimetastatic effects and suppressed the colonization ability of the lung cancer cells, suggesting a therapeutic potential for the synthesized compounds in lung cancer treatment. Full article

Chiral glutamide-derived lipids form self-assembled fibrous molecular gels that can be used as HPLC organic phases. In this study, HPLC separation efficiency was improved through the addition of branched amphiphilic glutamide lipids to the side chains of a terminally immobilized flexible polymer backbone. Poly(4-vinylpyridine) with a trimethoxysilyl group at one end was grafted onto the surface of porous silica particles (Sil−VP₁₅, polymerization degree = 15), and the pyridyl side chains were quaternized with a glutamide lipid having a bromide group (BrG). Elemental analysis indicated that the total amount of the organic phase of the prepared stationary phase (Sil−VPG₁₅) was 38.0 wt%, and the quaternization degree of the pyridyl groups was determined to be 32.5%. Differential scanning calorimetric analysis of a methanol suspension of Sil−VPG₁₅ indicated that the G moieties formed a highly ordered structure below the phase transition temperature even on the silica surface, and the ordered G moieties exhibited a gel-to-liquid crystalline phase transition. Compared with a commercially available octadecylated silica column, the Sil−VPG₁₅ stationary phase showed high selectivity toward polycyclic aromatic hydrocarbons, and particularly excellent separations were obtained for geometrical and positional isomers. Sil−VPG₁₅ also showed highly selective separation for phenol derivatives, and bio-related molecules containing phenolic groups such as steroids were successfully separated. These separation abilities are probably due to multiple interactions between the elutes and the highly ordered functional groups, such as the pyridinium and amide groups, on the highly ordered molecular gel having self-assembling G moieties. Full article

We report on formation of a bicontinuous double gyroid phase by a wedge-shaped amphiphilic mesogen, pyridinium 4′-[3″,4″,5″-tris-(octyloxy)benzoyloxy]azobenzene-4-sulfonate. It is found that this compound can self-organize in zeolite-like structures adaptive to environmental conditions (e.g., temperature, humidity, solvent vapors). Depending on the type of the phase, the structure contains 1D, 2D, or 3D networks of nanometer-sized ion channels. Of particular interest are bicontinuous phases, such as the double gyroid phase, as they hold promise for applications in separation and energy. Specially designed environmental cells compatible with grazing-incidence X-ray scattering and atomic force microscopy enable simultaneous measurements of structural parameters/morphology during vapor-annealing treatment at different temperatures. Such in-situ approach allows finding the environmental conditions at which the double gyroid phase can be formed and provide insights on the supramolecular structure of thin films at different spatial levels. Full article

This study was focused on the estimation of the targeted modification of 1,4-DHP core with (1) different alkyl chain lengths at 3,5-ester moieties of 1,4-DHP (C₁₂, C₁₄ and C₁₆); (2) N-substituent at position 1 of 1,4-DHP (N-H or N-CH₃); (3) substituents of pyridinium moieties at positions 2 and 6 of 1,4-DHP (H, 4-CN and 3-Ph); (4) substituent at position 4 of 1,4-DHP (phenyl and napthyl) on physicochemical properties of the entire molecules and on the characteristics of the obtained magnetoliposomes formed by them. It was shown that thermal behavior of the tested 1,4-DHP amphiphiles was related to the alkyl chains length, the elongation of which decreased their transition temperatures. The properties of 1,4-DHP amphiphile monolayers and their polar head areas were determined. The packing parameters of amphiphiles were in the 0.43–0.55 range. It was demonstrated that the structure of 1,4-DHPs affected the physicochemical properties of compounds. “Empty” liposomes and magnetoliposomes were prepared from selected 1,4-DHP amphiphiles. It was shown that the variation of alkyl chains length or the change of substituents at positions 4 of 1,4-DHP did not show a significant influence on properties of liposomes. Full article

Asphaltenes are heavy petroleum crude oil components which limit the production of petroleum crude oil due to their aggregation and their stabilization for all petroleum crude oil water emulsions. The present study aimed to modify the chemical structures of isolated asphaltenes by converting them into amphiphilic polymers containing ionic liquid moieties (PILs) to demulsify the emulsion and replace the asphaltene layers surrounding the oil or water droplets in petroleum crude oil emulsions. The literature survey indicated that no modification occurred to produce the PILs from the asphaltenes. In this respect, the asphaltenes were modified via oxidation of the lower aliphatic chain through carboxylation followed by conversion to asphaltene acid chloride that reacted with ethoxylated N-alkyl pyridinium derivatives. Moreover, the carboxylation of asphaltenes was carried out through the Diels–Alder reaction with maleic anhydride that was linked with ethoxylated N-alkyl pyridinium derivatives to produce amphiphilic asphaltene PILs. The produced PILs from asphaltenes acid chloride and maleic anhydride were designated as AIL and AIL-2. The chemical structure and thermal stability of the polymeric asphaltene ionic liquids were evaluated. The modified structure of asphaltenes AIL and AIL-2 exhibited different thermal characteristics involving glass transition temperatures (T_g) at −68 °C and −45 °C, respectively. The new asphaltenes ionic liquids were adsorbed at the asphaltenes surfaces to demulsify the heavy petroleum crude emulsions. The demulsification data indicated that the mixing of AIL and AIL-2 100 at different ratios with ethoxylated N-alkyl pyridinium were demulsified with 100% of the water from different compositions of O:W emulsions 50:50, 90:10, and 10:90. The demulsification times for the 50:50, 90:10, and 10:90 O:W emulsions were 120, 120, and 60 min, respectively. The interaction of the PILs with asphaltene and mechanism of demulsification was also investigated. Full article

We have prepared a series of pyridinium-based gemini amphiphiles. They exhibit thermotropic liquid–crystalline behavior depending on their alkyl chain lengths and anion species. By adjusting the alkyl chain lengths and selecting suitable anions, we have obtained an ionic amphiphile that exhibits a normal-type bicontinuous cubic phase from 38 °C to 12 °C on cooling from an isotropic phase. In the bicontinuous cubic liquid–crystalline assembly, the pyridinium-based ionic parts align along a gyroid minimal surface forming a 3D continuous ionic domain while their ionophobic alkyl chains form 3D branched nanochannel networks. This ionic compound can form homogeneous mixtures with a lithium salt and the resultant mixtures keep the ability to form normal-type bicontinuous cubic phases. Ion conduction measurements have been performed for the mixtures on cooling. It has been revealed that the formation of the 3D branched ionophobic nanochannels does not disturb the ion conduction behavior in the ionic domain while it results in the conversion of the state of the mixtures from fluidic liquids to quasi-solids, namely highly viscous liquid crystals. Although the ionic conductivity of the mixtures is in the order of 10^–7 S cm^–1 at 40 °C, which is far lower than the values for practical use, the present material design has a potential to pave the way for developing advanced solid electrolytes consisting of two task-specific nanosegregated domains: One is an ionic liquid nano-domain with a 3D continuity for high ionic conductivity and the other is ionophobic nanochannel network domains for high mechanical strength. Full article

The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparticles varied from 58 to 513 nm, depending upon the 4-(N-alkylpyridinium)-1,4-DHP structure. Additionally, we have confirmed that only nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3 and 6, and by 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 were stable after two weeks of storage. The nanoparticles of these compounds were found to be homogenous in size distribution, ranging from 124 to 221 nm. The polydispersity index (PDI) values of 1,4-DHPs samples 3, 6, 10, and 11 were in the range of 0.10 to 0.37. We also demonstrated that the nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3, 6, and 9, and 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 had zeta-potentials from +26.07 mV (compound 6) to +62.80 mV (compound 11), indicating a strongly positive surface charge and confirming the relative electrostatic stability of these nanoparticle solutions. Transmission electron microscopy (TEM) images of nanoaggregates formed by 1,4-DHPs 3 and 11 confirmed liposome-like structures with diameters around 70 to 170 nm. The critical aggregation concentration (CAC) value interval for 4-(N-alkylpyridinium)-1,4-DHP was from 7.6 µM (compound 11) to 43.3 µM (compound 6). The tested 4-(N-alkylpyridinium)-1,4-DHP derivatives were able to quench the fluorescence of the binary 1,6-diphenyl-1,3,5-hexatriene (DPH)—1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) system, demonstrating hydrophobic interactions of 1,4-DHPs with phospholipids. Thus, 4-(N-dodecylpyridinium)-1,4-DHP derivative 3 quenched the fluorescence of the DPH–DPPC system more efficiently than the other 4-(N-alkylpyridinium)-1,4-DHP derivatives. Likewise the compound 3, also 4-(N-dodecylpyridinium)-1,4-DHP derivative 9 interacted with the phospholipids. Moreover, we have established that increasing the length of the alkyl chain at the quaternised nitrogen of the 4-(N-alkylpyridinium)-1,4-DHP molecule or the introduction of propargyl moieties in the 1,4-DHP molecule significantly influences the cytotoxicity on HT-1080 (human fibrosarcoma) and MH-22A (mouse hepatocarcinoma) cell lines, as well as the estimated basal cytotoxicity. Additionally, it was demonstrated that the toxicity of the 4-(N-alkylpyridinium)-1,4-DHP derivatives on the Gram-positive and Gram-negative bacteria species and eukaryotic microorganism depended on the presence of the alkyl chain length at the N-alkyl pyridinium moiety, as well as the number of propargyl groups. These lipid-like compounds may be proposed for the further development of drug formulations to be used in cancer treatment. Full article