Search Results (3,058)

The rise in the number of cancer cases and the dissemination of strains with multiple drug resistance in the world pose a serious threat to public health care and human well-being. The design and study of new chemotherapeutic agents for cancer and infectious diseases are hot topics in science. Hydrazones, a versatile and diverse class of chemical compounds, gained a lot of attention as a promising base for future drugs. In this paper, we report on the synthesis of eight new gold(III) complexes with hydrazones derived from pyridoxal-5′-phosphate and pyridoxal. The complexes are thoroughly characterized using IR, ¹H, ³¹P NMR, and mass spectroscopy. The cytotoxic effect of twelve various hydrazones derived from pyridoxal 5′-phosphate on both immortalized (HEK293T) and tumor (HCT116) human cell lines was estimated using the MTT assay. In addition, this contribution describes the antibacterial action of complexes of gold(III) and pyridoxal and pyridoxal 5′-phosphate-derived hydrazones, as well as the mixtures of the solutions containing tetrachloroaurate(III) and hydrazones, using the zone of inhibition test. Gold(III) complexes exhibit moderate antibacterial activity against both Gram-positive and Gram-negative bacteria, while free hydrazones show low cytotoxicity and thus could be considered relatively safe for humans. Full article

Alkaptonuria (AKU) is a rare metabolic disorder caused by homogentisate 1,2-dioxygenase (HGD) deficiency, leading to homogentisic acid (HGA) accumulation and ochronotic pigment deposition, which drug therapy cannot reverse. The process of pigment formation and deposition is still unclear. This study offers molecular insights into the polymeric structure, with the goal of developing future adjuvant strategies that can inhibit or reverse pigment formation, thereby complementing drug therapy in AKU. HGA polymerisation was examined under physiological, acidic, and alkaline conditions using liquid and solid phase nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and polyacrylamide gel electrophoresis. At physiological pH, HGA polymerised slowly, while alkaline catalysis accelerated pigment formation while retaining the HGA aromatic scaffold. During the process, EPR detected a semiquinone radical intermediate, consistent with an oxidative coupling mechanism. Reactivity profiling showed the diphenol ring was essential for polymerisation, while –CH₂COOH modifications did not impair reactivity. Pigments displayed a polydisperse molecular weight range (11–50 kDa) and a strong negative charge. Solid-state NMR has revealed the presence of phenolic ether and biphenyl linkages. Collectively, these identified structural motifs can serve as a foundation for future molecular targeting related to pigment formation. Full article

Five different 2,4-difluorobenzamide derivatives were synthesized and fully characterized by ¹H/¹³C/¹⁹F/2D NMR spectroscopy using DMSO-d₆ as solvent and MS. All compounds occur as rotation conformers resulting from the partial amide double bond with a solvent-dependent coalescence point. Temperature-dependent ¹H NMR techniques, as well as EXSY, were applied to determine the rate constants of exchange, and the resulting activation energy barriers were calculated. Regarding the N,N-diacylated piperazine, both conformers (syn and anti) were found in solution, whereas only the anti-conformer was found in the crystals. This result was verified by an XRD analysis. Single crystals of N,N-bis(2,4-difluorobenzoyl)piperazine 3b (monoclinic, space group P2₁/c, a = 7.2687(3), b = 17.2658(8), c = 6.9738(3) Å, β = 115.393(2)°, V = 790.65(6) ų, Z = 4, D_obs = 1.530 g/cm³) were obtained from a saturated chloroform solution. Full article

4,4′-substituted-2,2′-((hexahydro-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))bisphenols (1a–d) and 2,6-bis{[3-(2-hydroxy-5-substitutedbenzyl)octahydro-1H-benzimidazol-1-yl]methyl}-4-substitutedphenols (2a–b) were synthesized via microwave (MW) irradiation of aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo[8.8.1.1.^8,170.^2,70.^11,16]icosane 2 with p-substituted phenols. Microwave (MW) irradiation improved reaction rates and yields at 80 °C. Compounds 1a–d were racemic, and 2a–b were diastereomeric. NMR spectra revealed key signals for the perhydrobenzimidazole fragment, aromatic rings, and aminal carbons. Differences in the ¹³C NMR spectra highlighted structural variations, such as distinct carbonyl and methoxyl signals in 2d. MW irradiation at higher temperatures (100–120 °C) reduced yields of 1, especially for phenols with methyl (Me) and methoxy (OMe) groups, suggesting a shift toward the formation of compound 2. Additionally, higher temperatures led to polymerization byproducts, emphasizing the impact of MW energy on reaction pathways. These results provide valuable insights for designing molecules with potential applications in materials science and medicinal chemistry. Full article

The compound dichloro[bis(diisopropylphosphorimidoyl-κN-(4,6-dimethylpyrimidine-κN))pyrrole-κN]yttrium(III) was synthesized from one equivalent of NaL [L = 2,5-[ⁱPr₂P=N(Pym^Me)]₂NH(C₄H₂); Pym^Me = 4,6-dimethylpyrimidine] and YCl₃(THF)_3.5 and crystallized from toluene. X-ray quality crystals of LYCl₂ were obtained with one toluene solvent molecule in the asymmetric unit. The geometry, bond lengths and angles were analyzed and found to contain similar parameters to comparable structures in the literature, and the product was further characterized by NMR spectroscopy. To the best of our knowledge, this is the first reported seven-coordinate Y(III) complex supported by a pentadentate ligand wherein all five donor atoms are nitrogen. Full article

Formation damage sensitivity is a primary constraint on productivity in coalbed methane (CBM) reservoirs. Conventional experimental methods, which often employ crushed or plug coal samples, disrupt the natural fracture network, thereby overestimating matrix damage and underestimating fracture-related damage. In this study, synchronous comparative experiments were conducted using raw coal and briquette coal cores, integrated with scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR) analyses to characterize coal composition and pore structure. This approach elucidates the underlying mechanisms controlling reservoir sensitivity. The main findings are as follows: The dual-sample comparative system reveals substantial deviations in traditional experimental assessments. Due to post-dissolution compaction, briquette coal samples overestimate acid sensitivity while underestimating water sensitivity. Stress sensitivity is primarily attributed to the irreversible compression of natural fractures. Differences in acid sensitivity are governed by structural integrity: mineral dissolution leads to collapse in briquette coal, whereas fractures help maintain stability in raw coal. Raw coal exhibits a lower critical flow rate for velocity sensitivity and undergoes significant water sensitivity damage below 1 MPa. Both sample types show weak alkaline sensitivity, with damage acceleration observed within the pH range of 7 to 10. Full article

In recent years, apatite-based materials have garnered significant interest, particularly for applications in tissue engineering. Apatite is most commonly employed as a coating for metallic implants, as a component in composite materials, and as scaffolds for bone and dental tissue regeneration. Among its various forms, hydroxyapatite (HAP) is the most widely used, owing to its natural occurrence in human and animal hard tissues. An emerging area of research involves the use of fluoride-substituted apatite, particularly fluorapatite (FAP), which can serve as a direct fluoride source at the implant site, potentially offering several biological and therapeutic advantages. However, substituting HAP with FAP may lead to unforeseen changes in material behavior due to the differing physicochemical properties of these two calcium phosphate phases. This study investigates the effects of replacing hydroxyapatite with fluorapatite in ceramic–polymer composite materials incorporating β-1,3-glucan as a bioactive polymeric binder. The β-1,3-glucan polysaccharide was selected for its proven biocompatibility, biodegradability, and ability to form stable hydrogels that promote cellular interactions. Nitrogen adsorption analysis revealed that FAP/glucan composites had a significantly lower specific surface area (0.5 m²/g) and total pore volume (0.002 cm³/g) compared to HAP/glucan composites (14.15 m²/g and 0.03 cm³/g, respectively), indicating enhanced ceramic–polymer interactions in fluoride-containing systems. Optical profilometry measurements showed statistically significant differences in profile parameters (e.g., Rp: 134 μm for HAP/glucan vs. 352 μm for FAP/glucan), although average roughness (Ra) remained similar (34.1 vs. 27.6 μm, respectively). Microscopic evaluation showed that FAP/glucan composites had smaller particle sizes (1 μm) than their HAP counterparts (2 μm), despite larger primary crystal sizes in FAP, as confirmed by TEM. XRD analysis indicated structural differences between the apatites, with FAP exhibiting a reduced unit cell volume (524.6 ų) compared to HAP (528.2 ų), due to substitution of hydroxyl groups with fluoride ions. Spectroscopic analyses (FTIR, Raman, ³¹P NMR) confirmed chemical shifts associated with fluorine incorporation and revealed distinct ceramic–polymer interfacial behaviors, including an upfield shift of PO₄³⁻ bands (964 cm⁻¹ in FAP vs. 961 cm⁻¹ in HAP) and OH vibration shifts (3537 cm⁻¹ in FAP vs. 3573 cm⁻¹ in HAP). The glucan polymer showed different hydrogen bonding patterns when combined with FAP versus HAP, as evidenced by shifts in polymer-specific bands at 888 cm⁻¹ and 1157 cm⁻¹, demonstrating that fluoride substitution significantly influences ceramic–polymer interactions in these bioactive composite systems. Full article

A novel heterobimetallic ruthenium(II)–gold(I) complex featuring a bridging bis(diphenylphosphino)butane (dppb) ligand was prepared and fully characterized. Single-crystal X-ray diffraction revealed a piano-stool geometry around Ru(II) with η⁶-cymene, two chlorido ligands, and one phosphorus atom from dppb, while the Au(I) center adopts a linear P–Au–Cl coordination. Structural integrity in the solution was confirmed by 1D and 2D NMR spectroscopy, while solution behavior was further monitored by variable solvent ³¹P NMR and UV/Vis spectroscopy, indicating that the organometallic Ru–arene core remains intact, whereas the chlorido ligands coordinated to Ru exhibit partial lability. Complementary characterization included elemental analysis, FTIR, and UV/Vis spectroscopy. Spectrofluorimetric and FRET analyses showed that Au(dppb), Ru(dppb), and the heterobimetallic AuRu complex bind to BSA with apparent constants of 1.41 × 10⁵, 5.12 × 10², and 2.66 × 10⁴ M⁻¹, respectively, following a static quenching mechanism. In vivo biological evaluation in Wistar rats revealed no significant hepatotoxicity or nephrotoxicity, with only mild and reversible histological alterations and preserved hepatocyte nuclear morphology. Hematological analysis indicated a statistically significant reduction in leukocyte populations, suggesting immunomodulatory potential, while elevated serum glucose levels point to possible endocrine or metabolic activity. These findings highlight compound structural stability and intriguing bioactivity profile, making it a promising platform for further organometallic drug development and testing. Full article

Chitosan is a promising biopolymer for drug delivery due to its biocompatibility, biodegradability, and low toxicity. However, its limited dispersibility in water restricts applications, which can be improved through organic acid salts. This study examined how acetic, lactic, glutamic, and citric acids influence the physicochemical, rheological, swelling, bioadhesive, stability, and cytotoxicity properties of chitosan hydrogels. Gels were prepared using varying chitosan-to-acid molar ratios (1:1; 1:1.2 for citrate) and characterized by NMR, FTIR, TGA, and XRD. Despite identical chitosan concentrations (2%, 3%, 3.5%), gels displayed distinct viscosity, swelling, and adhesion profiles depending on the acid. Lactate gels exhibited the most favorable overall performance, combining high viscosity (1555–6665 mPa·s), structural stability, and strong bioadhesion. Citrate gels showed the lowest viscosity (825–3550 mPa·s), cell viability, and stability but the highest bioadhesiveness, likely due to multivalent ionic interactions. Short-term stability tests revealed that low pH accelerated chitosan degradation, leading to viscosity loss up to ~90–95% within 30 days, particularly in citrate hydrogels. Cytotoxicity tests confirmed high biocompatibility, with all formulations maintaining cell viability above 80%. Overall, the findings highlight that organic acid selection is a critical determinant of chitosan gel behavior, offering guidance for tailoring safe, stable, and bioadhesive drug delivery systems. Full article

This study aims to generate foundational metabolomic data of aqueous humor (AH) in healthy horses and donkeys, and to investigate potential changes or trends in the metabolomic profile associated with age, sex or ocular pathology in horses. The AH metabolomic fingerprint from 5 donkeys and 35 equine eyes (17 controls, 8 with cataracts, 6 with retinal disease and 4 with anterior chamber disease (ACD)) were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A linear mixed-effects model, with individual horse as a random effect and group as a fixed effect, with multiple testing correction using the Benjamini–Hochberg false discovery rate (FDR) method was used to compare groups. The metabolomic profile of the donkeys and horse’s AH is very similar to that of other mammals. Threonine was higher in young horses (p = 0.04), and creatinine was elevated in males (p = 0.04). Compared with control groups, dimethyl sulfone was higher in the retina (p < 0.00) and cataract (p = 0.05) groups. Arginine (p = 0.05) and valine (p = 0.03) were lower in the retina group compared to controls. This study successfully characterized the AH metabolomic profile in healthy horses and donkeys and identified several metabolites that could be associated with ocular pathology, warranting further investigation to determine their potential as biomarkers of ocular disease. Full article

Carmustine (BCNU) is a powerful alkylating agent primarily used in the chemotherapeutic treatment of malignant brain tumors. However, its clinical application faces significant constraints due to its lipophilicity, low thermal stability, and rapid degradation in physiological environments. To tackle these challenges, our research aimed at the development and detailed characterization of α-cyclodextrin (α-CD) inclusion complexes (ICs) with BCNU employing three different synthesis techniques: co-grinding, cryomilling, and co-precipitation. The selected synthetic methods displayed variations dependent on the technique used, affecting the efficiency, inclusion ratios, and drug-loading capacities, with co-precipitation achieving the most favorable complexation parameters. Structural elucidation through ¹H NMR chemical shifts analysis indicated that only partial inclusion of BCNU occurred within α-CD in ICs produced via co-grinding, while cryomilling and co-precipitation allowed for complete inclusion. Multimodal spectroscopic analyses (FT-IR, UV-Vis, ¹³C CP MAS NMR, and ESI-MS) further substantiated the effective encapsulation of BCNU within α-CD, and systematic solubility assessments via Job’s continuous variation and the Benesi-Hildebrand method revealed a 1:1 host-guest stoichiometry. The ICs obtained were evaluated for BCNU release in vitro at pH levels of 4, 5, 6.5, and 7.4. The mechanism of BCNU drug release was determined to be Fickian diffusion, with the highest cumulative release noted in the acidic microenvironment. These findings collectively validate the effectiveness of α-CD as a functional excipient for the modulation of BCNU’s physicochemical properties through non-covalent complexation. This strategy shows potential for increasing the stability and solubility of BCNU, which may enhance its therapeutic effectiveness in the treatment of brain tumors. Full article

Background: Mycobacterium avium (Mav) is a leading cause of pulmonary disease among non-tuberculous mycobacteria (NTMs) due to its extensive antibiotic resistance profile. The essential Rel protein is a bifunctional enzyme, which is sensitive to environmental stress and regulates cellular guanosine-3′,5′-bispyrophosphate ((p)ppGpp). Increased levels of the alarmone thereby initiate a survival response, contributing to bacterial persistence and virulence. Objectives: MavRel harbors an unusual extension at the N-terminal domain (NTD), which we aim to characterize its possible regulatory role in maintaining (p)ppGpp homeostasis. We also studied whether the TGS domain retains its regulation capacity in MavRel and the binding propensity of the ACT domain to valine. Methods: Molecular dissection of MavRel was performed to generate a series of truncates to quantify the synthetase and hydrolase activities. Binding experiments with tRNA and valine were carried out via tryptophan quenching assay and NMR, respectively. Results: Bi-catalytic regulation of MavRel was found to be predominantly governed by the residues 37–50 at the NTD extension in its free state. The TGS domain was shown to harbor the capacity to bind with deacylated tRNA and represses synthetase activity to a lower degree compared to the NTD extension. We also characterized the dimeric Mav ACT-domain and the interacting residues contributing to its affinity with valine to function as a nutrient sensor. Conclusions: The mapping of the unique NTD regulatory element of MavRel reveals its functional relevance to coordinate the catalytic states of synthetase and hydrolase, hence underscores the prospect to drive inhibitor development targeting this novel site against Mav infections. Full article

The application of organic amendments and humic acids (HA) often ameliorates saline soils, but the mechanisms responsible for their positive action have never been fully clarified. HA from four different origins (Elliott soil—EHA, peat—PHA, leonardite—LHA and compost—CHA) and polyacrylic acid (PAA) were characterized by acid–base titrations and ¹H-NMR spectroscopy and tested in laboratory experiments by measuring changes in electric conductivity (EC) and pH following micro-additions of Na₂CO₃ or NaCl. The effective salinity amelioration potential (SAP_eff) of HA, which expresses the amount of Na₂CO₃ neutralized per unit weight of HA at a given pH, was calculated. PAA had the highest capacity of mitigation, corresponding to 49.9 mg Na₂CO₃ g⁻¹, followed by LHA, EHA and PHA, whose SAP_eff values were similar and only slightly lower, and with CHA having the lowest value (25.1 mg Na₂CO₃ g⁻¹ HA). All substances failed to display any effect at constant pH when NaCl was the only salt present. The dissociation of acid groups, when HA become exposed to a more alkaline pH, produces an excess of negative charges that attracts more cations within the diffuse double layer. Because of the slower diffusion of HA and their tendency to aggregate at high ionic strengths, this action reduces the osmolarity of the soil solution and therefore mitigates salinity stress. Full article

The applications of electromagnetic (EM) field treatment on water in agriculture have garnered increasing attention as a sustainable method to enhance plant growth, water-use efficiency, and metabolic performance. A growing body of evidence suggests that exposure to EM fields can affect water molecules, possibly by influencing hydrogen bonding dynamics, the structuring of water clusters, and electrokinetic properties of the water molecules. These alterations are thought to correlate with plant physiological performance. The methodology of the study was divided into two parts. The first part focused on the preparation of electromagnetically treated water. The second part involved applying this treated water to spinach plants. The present study investigates the physiological responses of Spinacia oleracea L. to irrigation with electromagnetically treated water (EMTW), focusing on elucidating the potential mechanisms that may underlie the observed effects. EMTW was generated using a solenoid-based system operating in dual-frequency ranges (100–1000 Hz and 10–100 kHz), which has been previously shown to influence both the microbiological and electrokinetic properties of aqueous systems. To evaluate the structural and functional implications of EMTW, a combined methodological approach was employed, integrating proton nuclear magnetic resonance (¹H-NMR) spectroscopy, density functional theory (DFT) modeling of water hydrogen bonds and clusters, and comprehensive plant physiological assessments. Plants were cultivated under both controlled and field conditions to assess consistency across environmental settings. Physiological measurements demonstrated that EMTW irrigation increased photosynthetic rate by ~80%, transpiration by 49–67%, stomatal conductance by 78–129%, intercellular CO₂ concentration by 42–80%, and chlorophyll content by 9.3–9.5% compared to control samples. Additionally, phenoloc and flavonoid contents were elevated by 7.4% and 7.6%, respectively, in field-grown plants. These enhancements were statistically significant (p < 0.001 or p < 0.01) under both laboratory and field conditions, confirming the robustness of the observed effects. Full article