Search Results (24)

Background: Guanine-rich DNA regions can fold into G-quadruplex (G4) structures, which are prevalent in telomeres and oncogene promoters, making them attractive targets for anticancer therapeutics. Small molecules capable of selectively stabilizing G4 DNA can disrupt telomerase activity and oncogene expression, offering a promising strategy for cancer intervention. Methods: A rationally designed series of DPPZ–anhydride-conjugated ligands (1 and 2) and their corresponding quaternized derivatives (1-q and 2-q) were synthesized to investigate the combined effects of π-extension, bromine substitution, and cationic modification on DNA recognition. The synthetic strategy relied on the incorporation of a highly planar DPPZ–anhydride scaffold to enhance π-surface area, followed by selective quaternization to introduce permanent positive charge and reinforce electrostatic interactions with the DNA backbone. All compounds were fully characterized by NMR and spectroscopic methods. The DNA-binding properties of the ligands were systematically evaluated toward duplex (ds-DNA) and G-quadruplex (G4-DNA) structures using UV–Vis absorption titration, fluorescence intercalator displacement (FID) assays, and competitive dialysis experiments. Quaternization markedly enhanced intrinsic binding constants and significantly reduced DC₅₀ values, particularly for G4-DNA. While bromine substitution increased overall binding affinity, it did not substantially improve topology selectivity. Among the series, compound 1-q exhibited the most favorable balance between affinity and G4 selectivity. Results: The interaction of the compounds with BSA was quantified using Stern–Volmer quenching constants, which demonstrated a clear trend of enhanced quenching efficiency upon modification. The binding strength followed a descending order of 1-q > 2-q > 1 > 2, highlighting the superior performance of the first series over the second. These findings indicate that the structural features of 1-q facilitate a more robust interaction within the hydrophobic pockets of the protein. Conclusions: Overall, the results demonstrate that strategic π-conjugation combined with electrostatic reinforcement provides an effective approach for the development of topology-selective DNA-binding ligands. Full article

Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by ¹H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H₂O₂. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against S. aureus. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering. Full article

Polyelectrolyte-based complexes have attracted attention, as the interaction of the oppositely charged components results in nanoparticle formation through an easy but highly efficient method, avoiding the use of strong solvents, extreme temperatures, and toxic chemicals. Sodium oleate (NaOL) is a widely used surfactant in the pharmaceutical industry due to its availability, eco-friendliness, and low cost. In the present study, the neutral-cationic block copolymer poly(oligo(ethylene glycol) methyl ether methacrylate)–b–quaternized poly(2-(dimethylamino) ethyl methacrylate) (POEGMA-b-Q(PDMAEMA)) is mixed with the anionic surfactant sodium oleate for the formation of nanoscale polyelectrolyte complexes through electrostatic interactions. Different weight ratios of copolymer to surfactant are studied. Then, the co-solvent protocol was implemented, and curcumin is successfully loaded in the formed particles for drug delivery applications. The size and morphology of the macromolecular complexes are examined via Dynamic Light Scattering (DLS) and Cryogenic Transmission Electron Microscopy (cryo-TEM). The methods that we have used have indicated that the polymer–surfactant complexes form spherical complexes, worm-like and vesicle-like structures. When curcumin was introduced, encapsulation was effectively achieved into micelles, giving rise to vesicle-like shapes. The success of curcumin encapsulation is confirmed by Ultraviolet–Visible absorption (UV–Vis) and fluorescence (FS) spectroscopy. POEGMA-b-Q(PDMAEMA)–sodium oleate polyelectrolyte complexes revealed promising attributes as efficient drug carrier systems for pharmaceutical formulations. Full article

Hydrophilic polymer–osmium complexes enhance electron transfer between enzymes and electrodes in biosensors. In this study, hydrophobic poly(4-vinylpyridine) (PVP) was quaternized with 2-bromoethanol to synthesize water-soluble PVP(Q)-C₂H₄OH polymers (MW 60,000 and 160,000). The resulting PVP(Q)-C₂H₄OH-Os(dmo-bpy)₂Cl complexes were verified by UV-Vis, FT-IR, 1H NMR, SEM-EDS, and zeta potential analyses, confirming successful quaternization and osmium coordination with good dispersion stability. Electrochemical tests (cyclic voltammetry, multi-potential step, amperometry) demonstrated that electrodes with quaternized mediators showed greatly enhanced catalytic currents for glucose (0–20 mM), with sensitivities of 6.9791 (MW 60,000) and 6.6279 μA·mM⁻¹·cm⁻² (MW 160,000), respectively, which were 6.6–10.3 times higher than those of non-quaternized polymers. Selectivity tests showed negligible interference from common species such as ascorbic acid, dopamine, uric acid, and serotonin. Continuous glucose monitoring (CGM) electrodes were fabricated by immobilizing the mediator and glucose dehydrogenase on silanized Au electrodes. SEM, scan rate, and impedance analyses confirmed stable binding. The modified electrodes showed strong linearity (R² = 0.992) and high sensitivity (2.56 μA·mM⁻¹·cm⁻²), and good stability, maintaining ~82% activity for seven days. Human plasma testing validated accurate glucose detection (6.05 mM), consistent with physiological levels. Overall, quaternized PVP(Q) mediators significantly improved solubility and electron transfer, enabling the development of a stable, selective glucose sensor suitable for CGM applications. Full article

The development and application of antimicrobial coatings has become increasingly important in both medical and industrial settings due to the rising threat of microbial contamination and antibiotic resistance. This paper focuses on the formulation, characterization, and investigation of coatings based on quaternized polysulfone, which are designed to encapsulate two broad-spectrum antimicrobial drugs with complementary activity, amphotericin B (AmB) and norfloxacin (NFX), with the primary aim of inhibiting pathogen colonization on surgical instruments. Structural characterization using FTIR, ¹H-NMR, and UV-Vis spectroscopy, along with supramolecular analysis via X-ray diffraction and polarized optical microscopy (POM), revealed strong physical interactions between the drugs and the quaternized polysulfone matrix. Scanning electron microscopy (SEM) confirmed a uniform distribution of the antimicrobial agents within the polymeric matrix. Surface wettability, assessed through water contact angle measurements, indicated moderate hydrophilicity (70–90°). The coatings also exhibited notable antioxidant activity, showing a 12-fold increase in DPPH radical inhibition compared to the control. Furthermore, all formulations demonstrated strong antimicrobial efficacy against three reference strains frequently associated with hospital-acquired infections, S. aureus, E. coli, and C. albicans, with inhibition zones ranging from 32 to 39.67 mm for bacterial strains and 13.86 to 20.86 mm for C. albicans. These data points indicate that these materials may be useful as antimicrobial coatings. Full article

Nowadays, nitrate ions and azo dyes are a significant source of water pollution due to their high toxicity, persistence, and potential to be carcinogenic. Both contaminants are the result of anthropogenic sources, such as sewage or industrial wastewater discharge; the first one results also as a consequence of the intensive use of fertilizers. In this work we report the use of a new quaternized pentablock copolymer (PTBr) for the removal of nitrate ions and methyl orange (MO) dye from water by adsorption processes. Morphological, chemical, and thermal properties of the pentablock copolymer were investigated, respectively, by scanning electron microscopy (SEM), Attenuated Total Reflectance Infrared Spectroscopy (ATR-FTIR) (FT-IR), and X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) analyses. Anionic removal ability and adsorption rate in water solutions containing either a single contaminant species or a mix of the two contaminants were studied by UV–VIS absorbance spectroscopy as a function of time and initial concentration. The presence of imidazole groups confers on PTBr a positive charge and a hydrophilic character that are responsible for an effective removal of anions from water. PTBr film reports an adsorption efficiency of 10.15 mg/g for nitrate removal and this value is in line with others reported in the literature. In the case of the simultaneous presence of nitrate and MO, it is found that nitrate ions removal is slightly affected by the presence of the dye, since both contaminants compete for electrostatic interaction with imidazole groups. On the contrary, the dye removal does not show significant change with or without the presence of nitrate ions, probably due to other kinds of interaction that it can establish with the polymer surface (π-π interaction). The adsorption process and the related mechanisms are described using kinetic and isothermal models. Despite a certain reduction in the adsorption efficiency for one of the investigated contaminants, the results confirm the possibility of using the quaternized pentablock copolymer for the co-adsorption of both inorganic and organic anions. Full article

The focus of the present study is on the fabrication of effective and eco-friendly hybrid electrospun materials based on poly(L-lactide-co-D,L-lactide) (PLDLLA), Fe₃O₄ and ZnO with an appropriate design for antioxidant and photocatalytic performance. The design of the fibrous materials was purposely tailored in one step by electrospinning and simultaneous electrospinning/electrospraying. Electrospinning of PLDLLA and its mixture with Fe₃O₄ resulted in the fabrication of materials with design type “in”. Furthermore, the surface of the electrospun PLDLLA and Fe₃O₄-in-PLDLLA was decorated with ZnO particles by simultaneous electrospraying, thus materials with design type “on” were obtained. In this case, quaternized N,N,N-trimethyl chitosan iodide (QCOS) was used as a sticking agent of ZnO particles onto the fiber’s surface. Different structures and morphologies of the electrospun materials were observed by SEM equipped with EDX and TEM. TGA and XRD analyses show that the presence of inorganic particles had an impact on the thermal properties and crystallinity of the electrospun materials. Furthermore, the material type “on” showed improved wettability with a water contact angle less than 90° compared to the material type “in” with an angle larger than 90°. In particular, the presence of Fe₃O₄ imparts complementary magnetic properties, while ZnO considerably increased the antioxidant activity of the fibrous materials. Materials with design type “on” displayed over 70% radical scavenging capacity in contrast to the material type “in” with less than 20% capacity within 30 min of contact. Moreover, the purposely tailored design type “on” materials provided excellent photocatalytic degradation of model organic pollutant methylene blue dye under UV light irradiation even after 5-fold use, and at the end of the fifth cycle these materials degraded more than 90% of the dye. These results reveal not only a strategy for the fabrication of electrospun hybrid bio-based materials with targeted design but also provide a promising, simple and effective way for mitigating water pollution. Full article

The present study concerns the preparation of hybrid nanostructures composed of carbon dots (CDs) synthesized in our lab and a double-hydrophilic poly(2-dimethylaminoethyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate) (P(DMAEMA-co-OEGMA)) random copolymer through electrostatic interactions between the negatively charged CDs and the positively charged DMAEMA segments of the copolymer. The synthesis of P(DMAEMA-co-OEGMA) copolymer was conducted through RAFT polymerization. Furthermore, the copolymer was converted into a strong cationic random polyelectrolyte through quaternization of the amine groups of DMAEMA segments with methyl iodide (CH₃I), and it was subsequently utilized for the complexation with the carbon dots. The molecular, physicochemical, and photophysical characterization of the aqueous solution of the copolymers and their hybrid nanoparticles was conducted using dynamic and electrophoretic light scattering (DLS, ELS) and spectroscopic techniques, such as UV-Vis, fluorescence (FS), and FT-IR spectroscopy. In addition, studies of their aqueous solution using DLS and ELS showed their responsiveness to external stimuli (pH, temperature, ionic strength). Finally, the interaction of selected hybrid nanoparticles with iron (III) ions was confirmed through FS spectroscopy, demonstrating their potential application for heavy metal ions sensing. Full article

Fascaplysin is a marine alkaloid which is considered to be a lead drug candidate due to its diverse and potent biological activity. As an anticancer agent, fascaplysin holds a great potential due to the multiple targets affected by this alkaloid in cancer cells, including inhibition of cyclin-dependent kinase 4 (CDK4) and induction of intrinsic apoptosis. At the same time, the studies on structural optimization are hampered by its rather high toxicity, mainly caused by DNA intercalation. In addition, the number of methods for the syntheses of its derivatives is limited. In the current study, we report a new two-step method of synthesis of fascaplysin derivatives based on low temperature UV quaternization for the synthesis of thermolabile 9-benzyloxyfascaplysin and 6-tert-butylfascaplysin. 9-Benzyloxyfascaplysin was used as the starting compound to obtain 9-hydroxyfascaplysin. However, the latter was found to be chemically highly unstable. 6-tert-Butylfascaplysin revealed a significant decrease in DNA intercalation when compared to fascaplysin, while cytotoxicity was only slightly reduced. Therefore, the impact of DNA intercalation for the cytotoxic effects of fascaplysin and its derivatives needs to be questioned. Full article

Stimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-b-poly(4-vinyl pyridine)-b-poly(ethylene oxide) (SVE) triblock terpolymer in order to achieve a selective responsivity to various diols. For this purpose, a reproducible method was established for P4VP block quaternization at a defined ratio, confirming the reaction yield by ¹¹B, ¹H NMR. Then, a reproducible self-assembly protocol is designed for preparing stable micelles from functionalized stimuli-responsive triblock terpolymers, which are characterized by light scattering and by cryogenic transmission electron microscopy. In addition, UV-Vis spectroscopy is used to monitor the boron-ester bonding and hydrolysis with alizarin as a model drug and to study encapsulation and release of this drug, induced by sensing with three geminal diols: fructose, galactose and ascorbic acid. The obtained results show that only the latter, with the vicinal diol group on sp²-hybridized carbons, was efficient for alizarin release. Therefore, the post-polymerization method for triblock terpolymer functionalization presented in this study allows for preparation of specific stimuli-responsive systems with a high potential for targeted drug delivery, especially for cancer treatment. Full article

The electrostatic complexation between double hydrophilic block copolymers (DHBCs) and a model porphyrin was explored as a means for the development of polyion complex micelles (PICs) that can be utilized as photosensitive porphyrin-loaded nanoparticles. Specifically, we employed a poly(2-(dimethylamino) ethyl methacrylate)-b-poly[(oligo ethylene glycol) methyl ether methacrylate] (PDMAEMA-b-POEGMA) diblock copolymer, along with its quaternized polyelectrolyte copolymer counterpart (QPDMAEMA-b-POEGMA) and 5,10,15,20-tetraphenyl-21H,23H-porphine-p,p′,p″,p′′′-tetrasulfonic acid tetrasodium hydrate (TPPS) porphyrin. The (Q)PDMAEMA blocks enable electrostatic binding with TPPS, thus forming the micellar core, while the POEGMA blocks act as the corona of the micelles and impart solubility, biocompatibility, and stealth properties to the formed nanoparticles. Different mixing charge ratios were examined aiming to produce stable nanocarriers. The mass, size, size distribution and effective charge of the resulting nanoparticles, as well as their response to changes in their environment (i.e., pH and temperature) were investigated by dynamic and electrophoretic light scattering (DLS and ELS). Moreover, the photophysical properties of the complexed porphyrin along with further structural insight were obtained through UV-vis (200-800 nm) and fluorescence spectroscopy measurements. Full article

In recent years, polymers with stimuli-responsive properties have been increasingly reported on due to their diverse applications. However, most of the studies have only focused on the performance of polymers under specific scenarios. The laws of changes in the properties in response to various external stimuli have been less systematically and quantitatively studied. In this paper, we prepared an amphiphilic polymer (PadaMX and PAdaM3QA−X) with temperature-, pH-, ion-, and β-cyclodextrin (β-CD)-responsive properties. According to the cloud point tested by the UV-Vis method, the lower critical soluble temperature (LCST) of PAdaM3QA−10% was more sensitive to a change in pH and less sensitive to a change in ions compared with PadaM3 due to quaternized side chains with a stronger intramolecular mutual repulsion. We then fabricated the coatings with responsive properties by immobilizing the adamantyl groups on β-CD-modified surfaces. The hydrophilicity of the coatings was improved after quaternization, as proven by the water contact angle (WCA) measurement. The antifouling and antibacterial performance was further evaluated via the fluorescence intensity of bovine serum albumin (BSA) adsorbed on the surfaces and the spread plate method. A 78.4% BSA desorption rate and a 96.8% sterilization rate were achieved by the PAdaM3QA−10% coating. In summary, this work prepared a multiple-stimuli-responsive amphiphilic copolymer for antifouling and antibacterial functionality via a “resistance–kill–release” mechanism. Full article

A synthesis of 3-(3,5-difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodides with ethyl or nonyl ester groups at positions 3 and 5 was performed. Treatment of the corresponding 2’,6’-dimethyl-1’,4’-dihydro-[3,4’-bipyridine]-3’,5’-dicarboxylates with Selectfluor^® followed by quaternization of pyridine moiety in the obtained dialkyl 2,4-diacetyl-2,4-difluoro-3-(pyridin-3-yl)pentanedioates with methyl iodide gave the desired 3-(3,5-difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodides. This type of compound would be useful as synthetic lipids for further development of the delivery systems. The obtained target compounds were fully characterized by ¹H NMR, ¹⁹F NMR, ¹³C NMR, HRMS, IR and UV data. The estimation of self-assembling properties and characterization of the nanoparticles obtained by ethanol solution injection in an aqueous media were performed by dynamic light scattering (DLS) measurements. DLS measurement data showed that 3-(3,5-difluoro-3,5-bis((nonyloxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodide created liposomes with the average diameter of 300–400 nm and polydispersity index (PDI) value around 0.30–0.40, while 3-(3,5-difluoro-3,5-bis((ethyloxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodide formed a heterogeneous sample with PDI value 1, which was not prospective for delivery system development. Full article

Research on the improvement and fabrication of polymeric systems as non-viral gene delivery carriers is required for their implementation in gene therapy. Random copolymers have not been extensively utilized for these purposes. In this regard, double hydrophilic poly[(2-(dimethylamino) ethyl methacrylate)-co-(oligo(ethylene glycol) methyl ether methacrylate] [P(DMAEMA-co-OEGMA)] random copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The copolymers were further modified by quaternization of DMAEMA tertiary amine, producing the cationic P(QDMAEMA-co-OEGMA) derivatives. Fluorescence and ultraviolet–visible (UV–vis) spectroscopy revealed the efficient interaction of copolymers aggregates with linear DNAs of different lengths, forming polyplexes, with the quaternized copolymer aggregates exhibiting stronger binding affinity. Light scattering techniques evidenced the formation of polyplexes whose size, molar mass, and surface charge strongly depend on the N/P ratio (nitrogen (N) of the amine group of DMAEMA/QDMAEMA over phosphate (P) groups of DNA), DNA length, and length of the OEGMA chain. Polyplexes presented colloidal stability under physiological ionic strength as shown by dynamic light scattering. In vitro cytotoxicity of the empty nanocarriers was evaluated on HEK293 as a control cell line. P(DMAEMA-co-OEGMA) copolymer aggregates were further assessed for their biocompatibility on 4T1, MDA-MB-231, MCF-7, and T47D breast cancer cell lines presenting high cell viability rates. Full article

A series of N-methyl quaternized derivatives of poly(4-vinylpyridine) (PVP) were synthesized in high yields with different degrees of quaternization, obtained by varying the methyl iodide molar ratio and affording products with unexplored optical and solvation properties. The impact of quaternization on the physicochemical properties of the copolymers, and notably the solvation properties, was further studied. The structure of the synthesized polymers and the quaternization degrees were determined by infrared and nuclear magnetic spectroscopies, while their thermal characteristics were studied by differential scanning calorimetry and their thermal stability and degradation by thermogravimetric analysis (TG-DTA). Attention was given to their optical properties, where UV-Vis and diffuse reflectance spectroscopy (DRS) measurements were carried out. The optical band gap of the polymers was calculated and correlated with the degree of quaternization. The study was further orientated towards the solvation properties of the polymers in binary solvent mixtures that strongly depend on the degree of quaternization, enabling a better understanding of the key polymer (solute)-solvent interactions. The assessment of the underlying solvation phenomena was performed in a system of different ratios of DMSO/H₂O and the solvatochromic indicator used was Reichardt’s dye. Solvent polarity parameters have a significant effect on the visible spectra of the nitrogen quaternization of PVP studied in this work and a detailed path towards this assessment is presented. Full article