Bulky Polyfluorinated Terphenyldiphenylboranes: Water Tolerant Lewis Acids.

Protocols for the synthesis of the bulky polyfluorinated triarylboranes 2,6-(C6 F5 )2 C6 F3 B(C6 F5 )2 (1), 2,6-(C6 F5 )2 C6 F3 B[3,5-(CF3 )2 C6 H3 ] (2), 2,4,6-(C6 F5 )3 C6 H2 B(C6 F5 )2 (3), 2,4,6-(C6 F5 )3 C6 H2 B[3,5-(CF3 )2 C6 H3 ] (4) were developed. All boranes are water tolerant and according to the Gutmann-Beckett method, 1-3 display Lewis acidities larger than that of the prominent B(C6 F5 )3 .

Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-oxadiazole-2-thiol Scaffold.

Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, 8a-p) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, 8k, 8l and 8m proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds 8c, 8h, 8i, 8m, 8n and 8o showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects.

Post-Assembly Reactivity of N-Aryl Iminoboronates: Reversible Radical Coupling and Unusual B-N Dynamic Covalent Chemistry.

Post-assembly reaction of a dynamic covalent iminoboronate system following addition of Cp2 Co resulted in the formation of a series of new reductively coupled dianionic dimers via C-C bond formation. The dimers formed as a mixture of BN-containing isomeric products: diastereomers rac5 and meso5, with coupled five-membered rings, and enantiomeric rac6, with a fused six-membered ring bicyclic system from C-C bond formation and rearrangement of the B-N bonds. Each isomer was identified using 1 H NMR spectroscopy in combination with single crystal X-ray structure determination. Interestingly, interconversion between the coupled five-membered rings (rac5 ) and fused bicyclic systems (rac6 ) was found to occur through an unprecedented breaking and reforming of the B-N covalent bond. Further, the coupled products could be converted quantitatively back to their iminoboronate precursors with addition of the electron abstractor Ph3 C+ .

New Chitosan-Based Co-Delivery Nanosystem for Diabetes Mellitus Therapy.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug that mainly works by reducing insulin resistance, while curcumin (Cur) is a powerful antioxidant with an important hypoglycemic effect. Both drugs are associated with several drawbacks, such as reduced bioavailability and a short half-life time (Pio), as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, new co-delivery (Pio and Cur) chitosan-based nanoparticles (CS-Pio-Cur NPs) were developed and compared with simple NPs (CS-Pio/CS-Cur NPs). The NPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). In addition, the entrapment efficiency (EE) and loading capacity (LC), as well as the release profile, of the APIs (Pio and Cur) from the CS-APIs NPs in simulated fluids (SGF, SIF, and SCF) were also assessed. All the CS-APIs NPs presented a small particle size (PS) (211.6-337.4 nm), a proper polydispersity index (PI) (0.104 and 0.289), and a positive zeta potential (ZP) (21.83 mV-32.64 mV). Based on the TEM results, an amorphous state could be attributed to the CA-APIs NPs, and the TEM analysis showed a spherical shape with a nanometric size for the CS-Pio-Cur NPs. The FT-IR spectroscopy supported the successful loading of the APIs into the CS matrix and proved some interactions between the APIs and CS. The CS-Pio-Cur NPs presented increased or similar EE (85.76% ± 4.89 for Cur; 92.16% ± 3.79 for Pio) and LC% (23.40% ± 1.62 for Cur; 10.14% ± 0.98 for Pio) values in comparison with simple NPs, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 22.31% ± 0.94), and CS-Pio NPs (EE = 93.67% ± 0.89; LC = 11.24% ± 0.17), respectively. Finally, based on the release profile results, it can be appreciated that the developed co-delivery nanosystem, CS-Pio-Cur NPs, assures a controlled and prolonged release of Pio and Cur from the polymer matrix along the GI tract.

New Smart Bioactive and Biomimetic Chitosan-Based Hydrogels for Wounds Care Management.

Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels' structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs.

Synthesis of novel series of 3,5-disubstituted imidazo[1,2-d] [1,2,4]thiadiazoles involving SNAr and Suzuki-Miyaura cross-coupling reactions.

The first access to 3,5-disubstituted imidazo[1,2-d][1,2,4]thiadiazole derivatives is reported. The series were generated from 2-mercaptoimidazole, which afforded the key intermediate bearing two functional positions. The SNAr reactivity toward tosyl release at the C-3 position was investigated and a regioselective electrophilic iodination in C-5 position was performed to allow a novel C-C bond using Suzuki-Miyaura reaction. Palladium-catalyzed cross-coupling conditions were optimized. A representative library of various boronic acids was employed to establish the scope and limitations of the method. To complete this methodological study, the influence of the nature of the C-3 imidazo[1,2-d][1,2,4]thiadiazole substitutions on the arylation in C-5 was investigated.

The Impact of the Storage Conditions and Type of Clearomizers on the Increase of Heavy Metal Levels in Electronic Cigarette Liquids Retailed in Romania.

The growing popularity of electronic cigarettes has raised several public health concerns, including the risks associated with heavy metals exposure via e-liquids and vapors. The purpose of this study was to determine, using atomic absorption spectrometry, the concentrations of Pb, Ni, Zn, and Co in some commercially available e-liquid samples from Romania immediately after purchase and after storage in clearomizers. Lead and zinc were found in all investigated samples before storage. The initial concentrations of Pb ranged from 0.13 to 0.26 mg L-1, while Zn concentrations were between 0.04 and 0.07 mg L-1. Traces of nickel appeared in all investigated e-liquids before storage but in very small amounts (0.01-0.02 mg L-1). Co was below the detection limits. We investigated the influence of the storage period (1, 3, and 5 days), storage temperature (22 °C and 40 °C), and type of clearomizer. In most cases, the temperature rise and storage period increase were associated with higher concentrations of heavy metals. This confirms that storage conditions can affect metal transfer and suggests that the temperature of storage is another parameter that can influence this phenomenon.

New nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold: Design, synthesis, in silico and in vitro studies.

In this study we present design and synthesis of nineteen new nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold (NO-IND-TZDs) (6a-s), as a new safer and efficient multi-targets strategy for inflammatory diseases. The chemical structure of all synthesized derivatives (intermediaries and finals) was proved by NMR and mass spectroscopic analysis. In order to study the selectivity of NO-IND-TZDs for COX isoenzymes (COX-1 and COX-2) a molecular docking study was performed using AutoDock 4.2.6 software. Based on docking results, COX-2 inhibitors were designed and 6o appears as the most selective derivative which showed an improved selective index compared with indomethacin (IND) and diclofenac (DCF), used as reference drugs. The biological evaluation of 6a-s, using in vitro assays has included the anti-inflammatory and antioxidant effects as well as the nitric oxide (NO) release. Referring to the anti-inflammatory effects, the most active compound was 6i, which was more active than IND and aspirin (ASP) in term of denaturation effect, on bovine serum albumin (BSA), as indirect assay to predict the anti-inflammatory effect. An appreciable anti-inflammatory effect, in reference with IND and ASP, was also showed by 6k, 6c, 6q, 6o, 6j, 6d. The antioxidant assay revealed the compound 6n as the most active, being 100 times more active than IND. The compound 6n showed also the most increase capacity to release NO, which means is safer in terms of gastro-intestinal side effects. The ADME-Tox study revealed also that the NO-IND-TZDs are generally proper for oral administration, having optimal physico-chemical and ADME properties. We can conclude that the compounds 6i and 6n are promising agents and could be included in further investigations to study in more detail their pharmaco-toxicological profile.

Multi-Approach Assessment for Stress Evaluation in Rainbow Trout Females, Oncorhynchus mykiss (Walbaum, 1792) from Three Different Farms during the Summer Season.

Blood biochemistry parameters are valuable tools for monitoring fish health. Their baseline values are still undefined for a multitude of farmed fish species. In this study, changes in the blood profile of rainbow trout females (Oncorhynchus mykiss) from three farms were investigated using different biomarkers during the summer season. In the given context, the main water physicochemical parameters were investigated and twelve biochemical parameters were measured from blood samples of rainbow trout reared in the Fiad, Șoimul de Jos, and Strâmba farms. We selected these farms because the genetic background of the rainbow trout is the same, with all studied specimens coming from the Fiad farm, which has an incubation station. Forty-five samples were collected monthly (May to August) throughout summer to observe the changes in the blood profile of rainbow trout. Principal component analysis showed a clear separation both among the studied farms and months. Furthermore, significant correlations (p < 0.05) between the majority of the biochemical parameters were found, indicating that the environmental parameters can influence several blood parameters at the same time. The present study provides several useful norms for assessing the welfare of rainbow trout, indicating that the relationships among different parameters are important factors in interpreting the blood biochemical profiles.

Formulation and Characterization of New Polymeric Systems Based on Chitosan and Xanthine Derivatives with Thiazolidin-4-One Scaffold.

In the past many research studies have focused on the thiazolidine-4-one scaffold, due to the important biological effects associated with its heterocycle. This scaffold is present in the structure of many synthetic compounds, which showed significant biological effects such as antimicrobial, antifungal, antioxidant, anti-inflammatory, analgesic, antidiabetic effects. It was also identified in natural compounds, such as actithiazic acid, isolated from Streptomyces strains. Starting from this scaffold new xanthine derivatives have been synthetized and evaluated for their antibacterial and antifungal effects. The antibacterial action was investigated against Gram positive (Staphyloccoccus aureus ATCC 25923, Sarcina lutea ATCC 9341) and Gram negative (Escherichia coli ATCC 25922) bacterial strains. The antifungal potential was investigated against Candida spp. (Candida albicans ATCC 10231, Candida glabrata ATCC MYA 2950, Candida parapsilosis ATCC 22019). In order to improve the antimicrobial activity, the most active xanthine derivatives with thiazolidine-4-one scaffold (XTDs: 6c, 6e, 6f, 6k) were included in a chitosan based polymeric matrix (CS). The developed polymeric systems (CS-XTDs) were characterized in terms of morphological (aspect, particle size), physic-chemical properties (swelling degree), antibacterial and antifungal activities, toxicity, and biological functions (bioactive compounds loading, entrapment efficiency). The presence of xanthine-thiazolidine-4-one derivatives into the chitosan matrix was confirmed using Fourier transform infrared (FT-IR) analysis. The size of developed polymeric systems, CS-XTDs, ranged between 614 µm and 855 µm, in a dry state. The XTDs were encapsulated into the chitosan matrix with very good loading efficiency, the highest entrapment efficiency being recorded for CS-6k, which ranged between 87.86 ± 1.25% and 93.91 ± 1.41%, depending of the concentration of 6k. The CS-XTDs systems showed an improved antimicrobial effect with respect to the corresponding XTDs. Good results were obtained for CS-6f, for which the effects on Staphylococcus aureus ATCC 25923 (21.2 ± 0.43 mm) and Sarcina lutea ATCC 9341 (25.1 ± 0.28 mm) were comparable with those of ciprofloxacin (25.1 ± 0.08 mm/25.0 ± 0.1 mm), which were used as the control. The CS-6f showed a notable antifungal effect, especially on Candida parapsilosis ATCC 22019 (18.4 ± 0.42 mm), the effect being comparable to those of nystatin (20.1 ± 0.09 mm), used as the control. Based on the obtained results these polymeric systems, consisting of thiazolidine-4-one derivatives loaded with chitosan microparticles, could have important applications in the food field as multifunctional (antimicrobial, antifungal, antioxidant) packaging materials.