Search Results (7)

A thiourea-based colorimetric sensor incorporating polyethyleneimine (PEI) and chromophoric nitrophenyl groups was synthesized and utilized for detecting various anions. Structural characterization of the sensor was accomplished using FTIR and 1H-NMR spectroscopy. The sensor’s interactions and colorimetric recognition capabilities with different anions, including CI⁻, Br⁻, I⁻, F⁻, NO₃⁻, PF₆⁻, AcO⁻, H₂PO₄⁻, PO₄³⁻, and SO₄²⁻, were investigated via visual observation and UV/vis spectroscopy. Upon adding SO₄²⁻, F⁻, and AcO⁻ anions, the sensor exhibited distinct color changes from colorless to yellow and yellowish, while other anions did not induce significant color alterations. UV/vis spectroscopic titration experiments conducted in a DMSO/H₂O solution (9:1 volume ratio) demonstrated the sensor’s selectivity toward SO₄²⁻, F⁻, and AcO⁻. The data revealed that the formation of the main compounds and anion complexes was mediated by hydrogen bonding, leading to signal changes in the nitrophenyl thiourea-modified PEI spectrum. Full article

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target the actin-binding protein gelsolin which is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP₂-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP₂-binding domain of gelsolin in the gelsolin-actin complex through extensive ten-microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP₂-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex. Full article

Phosphatidylserine lipids are anionic molecules present in eukaryotic plasma membranes, where they have essential physiological roles. The altered distribution of phosphatidylserine in cells such as apoptotic cancer cells, which, unlike healthy cells, expose phosphatidylserine, is of direct interest for the development of biomarkers. We present here applications of a recently implemented Depth-First-Search graph algorithm to dissect the dynamics of transient water-mediated lipid clusters at the interface of a model bilayer composed of 1-palmytoyl-2-oleoyl-sn-glycero-2-phosphatidylserine (POPS) and cholesterol. Relative to a reference POPS bilayer without cholesterol, in the POPS:cholesterol bilayer there is a somewhat less frequent sampling of relatively complex and extended water-mediated hydrogen-bond networks of POPS headgroups. The analysis protocol used here is more generally applicable to other lipid:cholesterol bilayers. Full article

The development of polymeric carriers based on partially deacetylated chitin nanowhiskers (CNWs) and anionic sulfated polysaccharides is an attractive strategy for improved vaginal delivery with modified drug release profiles. This study focuses on the development of metronidazole (MET)-containing cryogels based on carrageenan (CRG) and CNWs. The desired cryogels were obtained by electrostatic interactions between the amino groups of CNWs and the sulfate groups of CRG and by the formation of additional hydrogen bonds, as well as by entanglement of carrageenan macrochains. It was shown that the introduction of 5% CNWs significantly increased the strength of the initial hydrogel and ensured the formation of a homogeneous cryogel structure, resulting in sustained MET release within 24 h. At the same time, when the CNW content was increased to 10%, the system collapsed with the formation of discrete cryogels, demonstrating MET release within 12 h. The mechanism of prolonged drug release was mediated by polymer swelling and chain relaxation in the polymer matrix and correlated well with the Korsmeyer–Peppas and Peppas–Sahlin models. In vitro tests showed that the developed cryogels had a prolonged (24 h) antiprotozoal effect against Trichomonas, including MET-resistant strains. Thus, the new cryogels with MET may be promising dosage forms for the treatment of vaginal infections. Full article

Anions are important hydrogen bond acceptors in a range of biological, chemical, environmental and medical molecular recognition processes. These interactions have been exploited for the design and synthesis of ditopic resorcinarenes as the hydrogen bond strength can be tuned through the modification of the substituent at the 2-position. However, many potentially useful compounds, especially those incorporating electron-withdrawing functionalities, have not been prepared due to the challenge of their synthesis: their incorporation slows resorcinarene formation that is accessed by electrophilic aromatic substitution. As part of our broader campaign to employ resorcinarenes as selective recognition elements, we need access to these specialized materials. In this article, we report a straightforward synthetic pathway for obtaining a 2-(carboxymethyl)-resorcinarene, and resorcinarene esters in general. We discuss the unusual conformation it adopts and propose that this arises from the electron-withdrawing nature of the ester substituents that renders them better hydrogen bond acceptors than the phenols, ensuring that each of them acts as a donor only. Density Functional Theory (DFT) calculations show that this conformation arises as a consequence of the unusual configurational isomerism of this compound and interruption of the archetypal hydrogen bonding by the ester functionality. Full article

Searching novel hypouricemic agents of high efficacy and safety has attracted a great attention. Previously, we reported the hypouricemic effect of Ganoderma applanatum, but its bioactives, was not referred. Herein, we report the hypouricemic effect of 2,5-dihydroxyacetophenone (DHAP), a compound screened from Ganoderma applanatum computationally. Serum parameters, such as uric acid (SUA), xanthine oxidase (XOD) activity, blood urea nitrogen (BUN), and creatinine were recorded. Real-time reverse transcription PCR (RT-PCR) and Western blot were exploited to assay RNA and protein expressions of organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9), uric acid transporter 1 (URAT1), and gastrointestinal concentrative nucleoside transporter 2 (CNT2). DHAP at 20, 40, and 80 mg/kg exerted excellent hypouricemic action on hyperuricemic mice, reducing SUA from hyperuricemic control (407 ± 31 μmol/L, p < 0.01) to 180 ± 29, 144 ± 13, and 139 ± 31 μmol/L, respectively. In contrast to the renal toxic allopurinol, DHAP showed some kidney-protective effects. Moreover, its suppression on XOD activity, in vivo and in vitro, suggested that XOD inhibition may be a mechanism for its hypouricemic effect. Given this, its binding mode to XOD was explored by molecular docking and revealed that three hydrogen bonds may play key roles in its binding and orientation. It upregulated OAT1 and downregulated GLUT9, URAT1, and CNT2 too. In summary, its hypouricemic effect may be mediated by regulation of XOD, OAT1, GLUT9, URAT1, and CNT2. Full article

The first betaine chloride tetrachloroidoferrate(III) double salt, (Hbet)₂Cl[FeCl₄] = (Hbet)Cl·(Hbet)[FeCl₄], was obtained from a solution of betaine hydrochloride (HbetCl) and FeCl₃∙6 H₂O in water. The crystal structure (orthorhombic, Pbcm, a = 6.2717(13), b = 12.841(3), c = 25.693(5) Å, Z = 4) is characterized by layers of tetrachloridoferrate(III) anions separated by chloride-bridged, H-bond mediated cationic (Hbet) dimers. The hydrogen bonding network in the crystal structure follows the Pearson HSAB (hard acid-soft base) concept: According to the Pearson concept, the chloride anions show high affinity to the carboxyl group (hard acid and base), and the tetrachloroidoferrate(III) anion preferentially interacts with the activated methyl donors (soft acid and base). These interactions between the COOH group, as hard H-bond donor, and chloride as hard acceptor besides those between the soft, activated methyl groups and the soft tetrachloridoferrate(III) anions are the major structure-directing forces in the crystal structure of (Hbet)₂Cl[FeCl₄]. Full article