Sensitive determination of ethosuximide in human fluids by electromembrane extraction coupled with high performance liquid chromatography ultraviolet spectroscopy

Ethosuximide (ETX) is a common antiepileptic drug in the first line of absence epilepsy. In this study, for the first time, an economical and efficient electro-membrane (EME) method for determination of ETX in a complex biological matrix using HPLC-UV has been developed. Factors affecting conventional EME were evaluated. 1-Octanol was immobilized in a polypropylene membrane and a voltage of 35 V was applied between two platinum electrodes for 15 min. The pH of acceptor and donor phases for ionization of ETX was adjusted to 13 and 11, respectively. Under optimal microextraction conditions, the enrichment factor was 21.02 and the linear range of ETX was 0.25 to 8.00 μg/mL with an acceptable R² ≥ 0.9986. Inter-day and intra-day precision and accuracy of the suggested method were calculated with RSD < 9.5% and relative error <7.0%, respectively. The mean relative recovery of ETX in the human saliva and plasma samples was 81.68% and 74.47, respectively; while limit of detection and quantification concentrations were 0.08 and 0.25 μg/mL, respectively. Furthermore, to evaluate the application of the method, plasma and saliva samples of volunteers administering a single dose of ETX were analyzed successfully by EME-HPLC-UV method.     

Comparing Singlet Oxygen Generation of Schiff Base Substituted Novel Silicon Phthalocyanines by Sonophotochemical and Photochemical Applications

Although the sonophotodynamic method has an effective therapeutic outcome for anticancer treatment compared with the photodynamic method, there are not enough related studies in the literature and this study aims to contribute to the development of sonophotodynamic studies. For this purpose, the Schiff base substituted silicon phthalocyanines were designed and synthesized as effective sensitizer candidates and the photophysicochemical and sonophotochemical features of the phthalocyanines were examined to increase singlet oxygen efficiency. The calculated Φ_Δ values indicate that the contribution of substituent groups improved the production of singlet oxygen compared with silicon (IV) phthalocyanine dichloride (SiPcCI₂) and also the sonophotochemical applications increased the singlet oxygen yields. The Φ_Δ values (Φ_Δ = 0.76 for axially bis-{4-[(E)-(pyridin-3-ylimino)methyl]phenol} substituted silicon (IV) phthalocyanine ( 2a ), 0.68 for axially bis-4-[(E)-{[(pyridin-3-yl)methyl]imino}methyl]phenol substituted silicon (IV) phthalocyanine ( 2b ) in photochemical study) reached to Φ_Δ = 0.98 for 2a , 0.94 for 2b in sonophotochemical study. This article will enrich the literature on increasing singlet oxygen yield.     

Electrochemical Sensing Platform Based on Graphene Oxide-chitosan for Simultaneous Determination of some Antihypertensive Drugs

The development of selective and simple methods for the determination of different analytes is of great interest. This is the first time to show the applicability of graphene oxide-chitosan (GO-CS) nanocomposite for designing an electrochemical nanosensor for determination of Amlodipine, Valsartan, and Hydrochlorothiazide, simultaneously. Differential pulse voltammetrics current of AML, HCT, and VAL increased linearly in the ranges of 0.1–110, 0.1–110, and 1–230 μM with LOD of 5.5×10⁻², 3.5×10⁻² and 8.6×10⁻² μM, respectively. Finally, GO-CS/GCE was used for the detection of these drugs in commercial tablets and compared with the reference method (HPLC).     

Steric,Electronic and Conformational Synergistic Effects in the Gold(I)-catalyzed α-C−H Bond Functionalization of Tertiary Amines**

Direct C−H bond functionalization is a useful strategy for the straightforward formation of C−C and C−Heteroatom bonds. In the present work, a unique approach for the challenging electrophilic Au-catalyzed α-C−H bond functionalization of tertiary amines is presented. Electronic, steric and conformational synergistic effects exerted by the use of a malonate unit in the substrate were key to the success of this transformation. This new reactivity was applied to the synthesis of tetrahydro-γ-carboline products which, under oxidative conditions, could be converted into valuable structural motifs found in bioactive alkaloid natural products.     

Porous and Water Stable 2D Hybrid Metal Halide with Broad Light Emission and Selective H2O Vapor Sorption

In this work we report a strategy for generating porosity in hybrid metal halide materials using molecular cages that serve as both structure-directing agents and counter-cations. Reaction of the [2.2.2] cryptand (DHS) linker with Pb^II in acidic media gave rise to the first porous and water-stable 2D metal halide semiconductor (DHS)₂Pb₅Br₁₄. The corresponding material is stable in water for a year, while gas and vapor-sorption studies revealed that it can selectively and reversibly adsorb H₂O and D₂O at room temperature (RT). Solid-state NMR measurements and DFT calculations verified the incorporation of H₂O and D₂O in the organic linker cavities and shed light on their molecular configuration. In addition to porosity, the material exhibits broad light emission centered at 617 nm with a full width at half-maximum (FWHM) of 284 nm (0.96 eV). The recorded water stability is unparalleled for hybrid metal halide and perovskite materials, while the generation of porosity opens new pathways towards unexplored applications (e.g. solid-state batteries) for this class of hybrid semiconductors.     

High-throughput Synthesis of Solution-Processable van der Waals Heterostructures through Electrochemistry

Two-dimensional van der Waals heterostructures (2D vdWHs) have recently gained widespread attention because of their abundant and exotic properties, which open up many new possibilities for next-generation nanoelectronics. However, practical applications remain challenging due to the lack of high-throughput techniques for fabricating high-quality vdWHs. Here, we demonstrate a general electrochemical strategy to prepare solution-processable high-quality vdWHs, in which electrostatic forces drive the stacking of electrochemically exfoliated individual assemblies with intact structures and clean interfaces into vdWHs with strong interlayer interactions. Thanks to the excellent combination of strong light absorption, interfacial charge transfer, and decent charge transport properties in individual layers, thin-film photodetectors based on graphene/In₂Se₃ vdWHs exhibit great promise for near-infrared (NIR) photodetection, owing to a high responsivity (267 mA W⁻¹), fast rise (72 ms) and decay (426 ms) times under NIR illumination. This approach enables various hybrid systems, including graphene/In₂Se₃, graphene/MoS₂ and graphene/MoSe₂ vdWHs, providing a broad avenue for exploring emerging electronic, photonic, and exotic quantum phenomena.     

Front Cover: Katritzky Salts for the Synthesis of Unnatural Amino Acids and Late-Stage Functionalization of Peptides (Eur. J. Org. Chem. 12/2023)

Peptide drug discovery often benefits from the large structural diversity permitted by unnatural amino acids (UAAs). Indeed, numerous approved peptide drugs include UAAs in their sequences. Therefore, innovative chemical approaches either to synthesize UAAs or to allow late-stage functionalization of peptides are emerging themes in peptide drug discovery. Thanks to the recent advances in deaminative strategies using alkylpyridiniums salts, often referred to as Katritzky salts, a variety of radical alkylation methods have been developed. In recent years the use of Katritzky salts have become popular in peptide chemistry due to their ease of preparation from a primary amine, which is a predominant functional group in amino acids. This review highlights the progress that has been made by using Katritzky salts in the synthesis of UAAs, late-stage peptide functionalization, and peptide macrocyclization.     

Generation of Haploid Spermatids on Silk Fibroin-Alginate-Laminin-Based Porous 3D Scaffolds

In vitro production of sperm is a desirable idea for fertility preservation in azoospermic men and prepubertal boys suffering from cancer. In this study, a biocompatible porous scaffold based on a triad mixture of silk fibroin (SF), alginate (Alg), and laminin (LM) is developed to facilitate the differentiation of mouse spermatogonia stem cells (SSCs). Following SF extraction, the content is analyzed by SDS-PAGE and stable porous 3D scaffolds are successfully prepared by merely Alg, SF, and a combination of Alg-SF, or Alg-SF-LM through freeze-drying. Then, the biomimetic scaffolds are characterized regarding the structural and biological properties, water absorption capacity, biocompatibility, biodegradability, and mechanical behavior. Neonatal mice testicular cells are seeded on three-dimensional scaffolds and their differentiation efficiency is evaluated using real-time PCR, flow cytometry, immunohistochemistry. Blend matrices showed uniform porous microstructures with interconnected networks, which maintained long-term stability and mechanical properties better than homogenous structures. Molecular analysis of the cells after 21 days of culture showed that the expression of differentiation-related proteins in cells that are developed in composite scaffolds is significantly higher than in other groups. The application of a composite system can lead to the differentiation of SSCs, paving the way for a novel infertility treatment landscape in the future.     

The Role of Mechanical Properties and Structure of Type I Collagen Hydrogels on Colorectal Cancer Cell Migration

Mechanical interactions between cells and their microenvironment play an important role in determining cell fate, which is particularly relevant in metastasis, a process where cells invade tissue matrices with different mechanical properties. In vitro, type I collagen hydrogels have been commonly used for modeling the microenvironment due to its ubiquity in the human body. In this work, the combined influence of the stiffness of these hydrogels and their ultrastructure on the migration patterns of HCT-116 and HT-29 spheroids are analyzed. For this, six different types of pure type I collagen hydrogels by changing the collagen concentration and the gelation temperature are prepared. The stiffness of each sample is measured and its ultrastructure is characterized. Cell migration studies are then performed by seeding the spheroids in three different spatial conditions. It is shown that changes in the aforementioned parameters lead to differences in the mechanical stiffness of the matrices as well as the ultrastructure. These differences, in turn, lead to distinct cell migration patterns of HCT-116 and HT-29 spheroids in either of the spatial conditions tested. Based on these results, it is concluded that the stiffness and the ultrastructural organization of the matrix can actively modulate cell migration behavior in colorectal cancer spheroids.     

Targeted Delivery of Anticancer Drug Loaded Charged PLGA Polymeric Nanoparticles Using Electrostatic Field

Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg⁻¹] versus DLNs-based chemotherapy [0.75 mg kg⁻¹]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.