RESUMO
The new chalcogenylation of phosphines using nBu4Nâ§XCN (X = S, Se) is described. The reaction in 1,2-dichloroethane at 120 °C provided the corresponding phosphine sulfides in good to high yields. The protocol could be extended to the synthesis of phosphinic acid derivatives as well as sulfurization of poly(styrene-co-4-styryldiphenylphosphine).
Assuntos
Calcogênios , Fosfinas , Compostos de Amônio Quaternário , Fosfinas/química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/síntese química , Calcogênios/química , Calcogênios/síntese química , Estrutura MolecularRESUMO
Nanostructured transition metal dichalcogenides (TMDCs) have garnered significant attention as prospective materials for the development of highly sensitive and versatile colorimetric sensors. This work explores the synthesis, characterization, and emerging applications of TMDC-based sensors, focusing on their unique structural aspects and inherent properties. The synthesis methods involve tailored fabrication techniques, such as chemical vapor deposition and hydrothermal processes, aimed at producing well-defined nanostructures that enhance sensor performance. Characterization techniques, including microscopy, spectroscopy, and surface analysis, are employed to elucidate the structural and chemical features of the nanostructured TMDCs. These analyses provide insights into the correlation between the material's morphology and its sensing capabilities. The colorimetric sensing mechanism relies on the modulation of optical properties in response to specific analytes, enabling rapid and visual detection. The emerging applications of TMDC-based colorimetric sensors span diverse fields, including environmental monitoring, healthcare, and industrial processes. The sensors exhibit high sensitivity, selectivity, and real-time response, making them ideal candidates for detecting various target analytes. Furthermore, their integration with complementary technologies such as microfluidics, can facilitate the development of on-site and point-of-care applications. This work highlights the interdisciplinary significance of nanostructured TMDC-based colorimetric sensors and underscores their potential contributions to addressing contemporary challenges in sensing technology.
Assuntos
Colorimetria , Nanoestruturas , Elementos de Transição , Nanoestruturas/química , Elementos de Transição/química , Calcogênios/químicaRESUMO
The noncovalent chalcogen interaction between SO2/SO3 and diazines was studied through a dispersion-corrected DFT Kohn-Sham molecular orbital together with quantitative energy decomposition analyses. For this, supramolecular circular chains of up to 12 molecules were built with the aim of checking the capability of diazine molecules to detect SO2/SO3 compounds within the atmosphere. Trends in the interaction energies with the increasing number of molecules are mainly determined by the Pauli steric repulsion involved in these σ-hole/π-hole interactions. But more importantly, despite the assumed electrostatic nature of the involved interactions, the covalent component also plays a determinant role in its strength in the involved chalcogen bonds. Noticeably, π-hole interactions are supported by the charge transfer from diazines to SO2/SO3 molecules. Interaction energies in these supramolecular complexes are not only determined by the S···N bond lengths but attractive electrostatic and orbital interactions also determine the trends. These results should allow us to establish the fundamental characteristics of chalcogen bonding based on its strength and nature, which is of relevance for the capture of sulfur oxides.
Assuntos
Calcogênios , Óxidos de Enxofre , Calcogênios/química , Óxidos de Enxofre/química , Eletricidade Estática , Modelos Moleculares , Dióxido de Enxofre/químicaRESUMO
The ability of thermoelectric materials to generate electricity in response to local temperature gradients makes them a potentially promising solution for the regulation of cellular functions and reconstruction of tissues. Biocompatibility of implants is a crucial attribute for the successful integration of thermoelectric techniques in biomedical applications. This work focuses on the in vitro and in vivo evaluation of biocompatibility for 12 typical chalcogenide thermoelectrics, which are composed of biocompatible elements. Ag2Se, SnSe, Bi2Se3, Bi2Te2.88Se0.12 and Bi2Te3, each with a released ion concentration lower than 10 ppm in extracts, exhibited favorable biocompatibility, including cell viability, adhesion, and hemocompatibility, as observed in initial in vitro assessments. Moreover, in vivo biocompatibility assessment, achieved by hematological and histopathological analyses in the rat subcutaneous model, further substantiated the biocompatibility of Ag2Se, Bi2Se3, and Bi2Te3, with each possessing superior thermoelectric performance at room temperature. This work offers robust evidence to promote Ag2Se, Bi2Se3, and Bi2Te3 as potential thermoelectric biomaterials, establishing a foundation for their future applications in biomedicine.
Assuntos
Materiais Biocompatíveis , Sobrevivência Celular , Calcogênios , Teste de Materiais , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Calcogênios/química , Ratos , Sobrevivência Celular/efeitos dos fármacos , Próteses e Implantes , Ratos Sprague-Dawley , Temperatura , Humanos , Adesão Celular/efeitos dos fármacos , Camundongos , MasculinoRESUMO
Quantum dots (QDs), a novel category of semiconductor materials, exhibit extraordinary capabilities in tuning optical characteristics. Their emergence in biophotonics has been noteworthy, particularly in bio-imaging, biosensing, and theranostics applications. Although conventional QDs such as PbS, CdSe, CdS, and HgTe have garnered attention for their promising features, the presence of heavy metals in these QDs poses significant challenges for biological use. To address these concerns, the development of Ag chalcogenide QDs has gained prominence owing to their near-infrared emission and exceptionally low toxicity, rendering them suitable for biological applications. This review explores recent advancements in Ag chalcogenide QDs, focusing on their synthesis methodologies, surface chemistry modifications, and wide-ranging applications in biomedicine. Additionally, it identifies future directions in material science, highlighting the potential of these innovative QDs in revolutionizing the field.
Assuntos
Calcogênios , Pontos Quânticos , Prata , Propriedades de Superfície , Pontos Quânticos/química , Prata/química , Humanos , Calcogênios/química , Raios Infravermelhos , Técnicas Biossensoriais/métodos , AnimaisRESUMO
Among various non-covalent interactions, selenium-centered chalcogen bonds (SeChBs) have garnered considerable attention in recent years as a result of their important contributions to crystal engineering, organocatalysis, molecular recognition, materials science, and biological systems. Herein, we systematically investigated π-hole-type SeâââO/S ChBs in the binary complexes of SeO2 with a series of O-/S-containing Lewis bases by means of high-level ab initio computations. The results demonstrate that there exists an attractive interaction between the Se atom of SeO2 and the O/S atom of Lewis bases. The interaction energies computed at the MP2/aug-cc-pVTZ level range from -4.68 kcal/mol to -10.83 kcal/mol for the SeâââO chalcogen-bonded complexes and vary between -3.53 kcal/mol and -13.77 kcal/mol for the SeâââS chalcogen-bonded complexes. The SeâââO/S ChBs exhibit a relatively short binding distance in comparison to the sum of the van der Waals radii of two chalcogen atoms. The SeâââO/S ChBs in all of the studied complexes show significant strength and a closed-shell nature, with a partially covalent character in most cases. Furthermore, the strength of these SeâââO/S ChBs generally surpasses that of the C/O-HâââO hydrogen bonds within the same complex. It should be noted that additional C/O-HâââO interactions have a large effect on the geometric structures and strength of SeâââO/S ChBs. Two subunits are connected together mainly via the orbital interaction between the lone pair of O/S atoms in the Lewis bases and the BD*(OSe) anti-bonding orbital of SeO2, except for the SeO2âââHCSOH complex. The electrostatic component emerges as the largest attractive contributor for stabilizing the examined complexes, with significant contributions from induction and dispersion components as well.
Assuntos
Calcogênios , Bases de Lewis , Oxigênio , Selênio , Enxofre , Bases de Lewis/química , Calcogênios/química , Selênio/química , Enxofre/química , Oxigênio/química , Modelos Moleculares , Ligação de Hidrogênio , Óxidos de Selênio/química , TermodinâmicaRESUMO
This study investigates the applicability of six transition metal dichalcogenides to efficient therapeutic drug monitoring of ten antiepileptic drugs using laser desorption/ionization-mass spectrometry. We found that molybdenum ditelluride and tungsten ditelluride are suitable for the sensitive quantification of therapeutic drugs. The contribution of tellurium to the enhanced efficiency of laser desorption ionization was validated through theoretical calculations utilizing an integrated model that incorporates transition-metal dichalcogenides and antiepileptic drugs. The results of our theoretical calculations suggest that the relatively low surface electron density for the tellurium-containing transition metal dichalcogenides induces stronger Coulombic interactions, which results in enhanced laser desorption and ionization efficiency. To demonstrate applicability, up to 120 patient samples were analyzed to determine drug concentrations, and the results were compared with those of immunoassay and liquid chromatography-tandem mass spectrometry. Agreements among these methods were statistically evaluated using the Passing-Bablok regression and Bland-Altman analysis. Furthermore, our method has been shown to be applicable to the simultaneous detection and multiplexed quantification of antiepileptic drugs.
Assuntos
Anticonvulsivantes , Monitoramento de Medicamentos , Monitoramento de Medicamentos/métodos , Humanos , Anticonvulsivantes/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Calcogênios/químicaRESUMO
Lung adenocarcinoma stands as a leading global cause of cancer-related fatalities, with current therapeutic approaches remaining unsatisfactory. Given the association between elevated oxidative markers and the aggressive nature of cancer cells (including multidrug resistance and metastatic potential) that can predict poor outcome of lung adenocarcinoma patients, any compounds that interfere with their aberrant redox biology should be rationally explored as innovative intervention strategies. This study was designed to screen potential anticancer activities within nine newly synthesized organochalcogen - compounds characterized by the presence of oxygen, sulfur, or selenium elements in their structure and exhibiting antioxidant activity - and systematically evaluated their performance against cisplatin, the cornerstone therapeutic agent for lung adenocarcinoma. Our methodology involved the establishment of optimal conditions for generating single tumor spheroids using A549 human lung adenocarcinoma cell line. The initiation interval for spheroid formation was determined to be four days in vitro (DIV), and these single spheroids demonstrated sustained growth over a period of 20 DIV. Toxic dose-response curves were subsequently performed for each compound after 24 and 48 h of incubation at the 12th DIV. Our findings reveal that at least two of the synthetic organochalcogen compounds exhibited noteworthy anticancer activity, surpassing cisplatin in key parameters such as lower LD (Lethal Dose) 50, larger drug activity area, and maximum amplitude of effect, and are promising drugs for futures studies in the treatment of lung adenocarcinomas. Physicochemical descriptors and prediction ADME (absorption, distribution, metabolism, and excretion) parameters of selected compounds were obtained using SwissADME computational tool; Molinspiration server was used to calculate a biological activity score, and possible molecule targets were evaluated by prediction with the SwissTargetPrediction server. This research not only sheds light on novel avenues for therapeutic exploration but also underscores the potential of synthetic organochalcogen compounds as agents with superior efficacy compared to established treatments.
Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Calcogênios , Cisplatino , Neoplasias Pulmonares , Esferoides Celulares , Humanos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Calcogênios/química , Calcogênios/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Células A549 , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Sobrevivência Celular/efeitos dos fármacosRESUMO
The ultimate goal of nanoparticle-based phototherapy is to suppress tumor growth. Photothermal therapy (PTT) and photothermal photodynamic therapy (PDT) are two types of physicochemical therapy that use light radiation with multiple wavelength ranges in the near-infrared to treat cancer. When a laser is pointed at tissue, photons are taken in the intercellular and intracellular regions, converting photon energy to heat. It has attracted much interest and research in recent years. The advent of transition materials dichalcogenides (TMDCs) is a revolutionary step in PDT/PTT-based cancer therapy. The TMDCs is a multilayer 2D nano-composite. TMDCs contain three atomic layers in which two chalcogens squash in the transition metal. The chalcogen atoms are highly reactive, and the surface characteristics of TMDCs help them to target deep cancer cells. They absorb Near Infrared (NIR), which kills deep cancer cells. In this review, we have discussed the history and mechanism of PDT/PTT and the use of TMDCs and nanoparticle-based systems, which have been practiced for theranostics purposes. We have also discussed PDT/PTT combined with immunotherapy, in which the cancer cell apoptosis is done by activating the immune cells, such as CD8+.
Assuntos
Neoplasias , Fotoquimioterapia , Terapia Fototérmica , Elementos de Transição , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Elementos de Transição/química , Elementos de Transição/farmacologia , Calcogênios/química , Calcogênios/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , AnimaisRESUMO
The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.
Assuntos
Calcogênios , Neoplasias , Elementos de Transição , Humanos , Neoplasias/tratamento farmacológico , Elementos de Transição/química , Calcogênios/química , Antineoplásicos/química , Antineoplásicos/farmacologia , AnimaisRESUMO
The synthesis and structural characterization of α-haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles with various counterions is reported herein, demonstrating a strategy for directed supramolecular dimerization in the solid state. The compounds were obtained through a recently discovered 1,3-dipolar cycloaddition reaction between nitriles and bifunctional 2-pyridylselenyl reagents, and their structures were confirmed by the X-ray crystallography. α-Haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles exclusively formed supramolecular dimers via four-center Se···N chalcogen bonding, supported by additional halogen bonding involving α-haloalkyl substituents. The introduction of halogens at the α-position of the substituent R in the selenadiazole core proved effective in promoting supramolecular dimerization, which was unaffected by variation of counterions. Additionally, the impact of cocrystallization with a classical halogen bond donor C6F3I3 on the supramolecular assembly was investigated. Non-covalent interactions were studied using density functional theory calculations and topological analysis of the electron density distribution, which indicated that all ChB, XB and HB interactions are purely non-covalent and attractive in nature. This study underscores the potential of halogen and chalcogen bonding in directing the self-assembly of functional supramolecular materials employing 1,2,4-selenadiazoles derived from recently discovered cycloaddition between nitriles and bifunctional 2-pyridylselenyl reagents.
Assuntos
Calcogênios , Halogênios , Dimerização , Reagentes de Ligações Cruzadas , NitrilasRESUMO
Here, iron chalcogenide thin films were developed for the first time by using the less hazardous electrodeposition technique at optimized conditions on an FTO glass substrate. The chalcogenides have different surface, morphological, structural, and optical properties, as well as an enzyme-free sensing behavior toward urea. Numerous small crystallites of about â¼20 to 25 nm for FeSe, â¼18 to 25 nm for FeTe, and â¼18 to 22 nm in diameter for FeSeTe are observed with partial agglomeration under an electron microscope, having a mixed phase of tetragonal and orthorhombic structures of FeSe, FeTe, and, FeSeTe, respectively. Profilometry, XRD, FE-SEM, HR-TEM, XPS, EDX, UV-vis spectroscopy, and FT-IR spectroscopy were used for the analysis of binary and ternary composite semiconductors, FeSe, FeTe, and FeSeTe, respectively. Electrochemical experiments were conducted with the chalcogenide thin films and urea as the analyte in phosphate-buffered media at a pH of â¼ 7.4 in the concentration range of 3-413 µM. Cyclic voltammetry was performed to determine the sensitivity of the prepared electrode at an optimized scan rate of 50 mV s-1. The electrodeposited chalcogenide films appeared with a low detection limit and satisfactory sensitivity, of which the ternary chalcogenide film has the lowest LOD of 1.16 µM and the maximum sensitivity of 74.22 µA µM-1 cm-2. The transition metal electrode has a very wide range of detection limit of 1.25-2400 µM with a short response time of 4 s. This fabricated biosensor is capable of exhibiting almost 75% of its starting activity after 2 weeks of storage in the freezer at 4 °C. Simple methods of preparation, a cost-effective process, and adequate electrochemical sensing of urea confirm that the prepared sensor is suitable as an enzyme-free urea sensor and can be utilized for future studies.
Assuntos
Calcogênios , Ferro , Ureia/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Calcogênios/químicaRESUMO
Organic dye-based agents with near-infrared (NIR)-II absorption have great potential for cancer theranostics because of the deeper tissue penetration and good biocompatibility. However, proper design is required to develop NIR-II-absorbing dyes with good optical properties. We proposed to construct chalcogen atom-modulated croconaine for NIR-II light-triggered photothermal theranostics. By introducing different chalcogen atoms (O, S, Se, or Te) into the structure of croconaine, the light absorption of croconaine can be precisely regulated from the NIR-I to the NIR-II range due to the heavy-atom effect. Especially, Te-substituted croconaine (CRTe) and its nanoformulations exhibit superior NIR-II responsiveness, a high photothermal conversion efficiency (70.6%), and good photostability. With their favorable tumor accumulation, CRTe-NPs from tumor regions can be visualized by NIR-II optoacoustic systems with high resolution and high contrast; meanwhile, their superior photothermal performance also contributes to efficient cell killing and tumor elimination upon 1064 nm laser irradiation. Therefore, this work provides an efficient strategy for the molecular design of NIR-II organic photothermal agents.
Assuntos
Calcogênios , Nanopartículas , Neoplasias , Humanos , Nanomedicina Teranóstica , Neoplasias/tratamento farmacológico , Corantes/química , Calcogênios/farmacologia , Nanopartículas/química , Fototerapia , Linhagem Celular TumoralRESUMO
In recent years, the non-covalent interactions between chalcogen centers have aroused substantial research interest because of their potential applications in organocatalysis, materials science, drug design, biological systems, crystal engineering, and molecular recognition. However, studies on π-hole-type chalcogenâââchalcogen interactions are scarcely reported in the literature. Herein, the π-hole-type intermolecular chalcogenâââchalcogen interactions in the model complexes formed between XO2 (X = S, Se, Te) and CH3YCH3 (Y = O, S, Se, Te) were systematically studied by using quantum chemical computations. The model complexes are stabilized via one primary XâââY chalcogen bond (ChB) and the secondary C-HâââO hydrogen bonds. The binding energies of the studied complexes are in the range of -21.6~-60.4 kJ/mol. The XâââY distances are significantly smaller than the sum of the van der Waals radii of the corresponding two atoms. The XâââY ChBs in all the studied complexes except for the SO2âââCH3OCH3 complex are strong in strength and display a partial covalent character revealed by conducting the quantum theory of atoms in molecules (QTAIM), a non-covalent interaction plot (NCIplot), and natural bond orbital (NBO) analyses. The symmetry-adapted perturbation theory (SAPT) analysis discloses that the XâââY ChBs are primarily dominated by the electrostatic component.
Assuntos
Calcogênios , Calcogênios/química , Ligação de Hidrogênio , Teoria Quântica , Eletricidade EstáticaRESUMO
Bacterial DNA phosphorothioate (PT) modification provides a specific anchoring site for sulfur-binding proteins (SBDs). Besides, their recognition patterns include phosphate links and bases neighboring the PT-modified site, thereby bringing about genome sequence-dependent properties in PT-related epigenetics. Here, we analyze the contributions of the DNA backbone (phosphates and deoxyribose) and bases bound with two SBD proteins in Streptomyces pristinaespiralis and coelicolor (SBDSco and SBDSpr). The chalcogen-hydrophobic interactions remained constantly at the anchoring site while the adjacent bases formed conditional and distinctive non-covalent interactions. More importantly, SBD/PT-DNA interactions were not limited within the traditional "4-bp core" range from 5'-I to 3'-III but extended to upstream 5'-II and 5'-III bases and even 5''-I to 5''-III at the non-PT-modified complementary strand. From the epigenetic viewpoint, bases 3'-II, 5''-I, and 5''-III of SBDSpr and 3'-II, 5''-II, and 5''-III of SBDSco present remarkable differentiations in the molecular recognitions. From the protein viewpoint, H102 in SBDSpr and R191 in SBDSco contribute significantly while proline residues at the PT-bound site are strictly conserved for the PT-chalcogen bond. The mutual and make-up mutations are proposed to alter the SBD/PT-DNA recognition pattern, besides additional chiral phosphorothioate modifications on phosphates 5'-II, 5'-II, 3'-I, and 3'-II.
Assuntos
Calcogênios , DNA , DNA/química , DNA Bacteriano/química , Proteínas de Bactérias/metabolismo , Fosfatos/químicaRESUMO
In this work, intra- and intermolecular halogen and chalcogen bonds (HlgBs and ChBs, respectively) present in the solid state of nucleic acids (NAs) have been studied at the RI-MP2/def2-TZVP level of theory. To achieve this, a Protein Data Bank (PDB) survey was carried out, revealing a series of structures in which Br/I or S/Se/Te atoms belonging to nucleobases or pentose rings were involved in noncovalent interactions (NCIs) with electron-rich species. The energetics and directionality of these NCIs were rationalized through a computational study, which included the use of Molecular Electrostatic Potential (MEP) surfaces, the Quantum Theory of Atoms in Molecules (QTAIM), and Non Covalent Interaction plot (NCIplot) and Natural Bonding Orbital (NBO) techniques.
Assuntos
Calcogênios , Ácidos Nucleicos , Cristalografia , Bases de Dados Factuais , HalogêniosRESUMO
Alzheimer's disease is becoming a growing problem increasing at a tremendous rate. Serotonin 5-HT6 receptors appear to be a particularly attractive target from a therapeutic perspective, due to their involvement not only in cognitive processes, but also in depression and psychosis. In this work, we present the synthesis and broad biological characterization of a new series of 18 compounds with a unique 1,3,5-triazine backbone, as potent 5-HT6 receptor ligands. The main aim of this research is to compare the biological activity of the newly synthesized sulfur derivatives with their oxygen analogues and their N-demethylated O- and S-metabolites obtained for the first time. Most of the new triazines displayed high affinity (Ki < 200 nM) and selectivity towards 5-HT6R, with respect to 5-HT2AR, 5-HT7R, and D2R, in the radioligand binding assays. For selected, active compounds crystallographic studies, functional bioassays, and ADME-Tox profile in vitro were performed. The exciting novelty is that the sulfur derivatives exhibit an agonistic mode of action contrary to all other compounds obtained to date in this chemical class herein and previously reported. Advanced computational studies indicated that this intriguing functional shift might be caused by presence of chalcogen bonds formed only by the sulfur atom. In addition, the N-demethylated derivatives have emerged highly potent antioxidants and, moreover, show a significant improvement in metabolic stability compared to the parent structures. The cholinesterase study present micromolar inhibitory AChE and BChE activity for both 5-HT6 agonist 19 and potent antagonist 5. Finally, the behavioral experiments of compound 19 demonstrated its antidepressant-like properties and slight ability to improve cognitive deficits, without inducing memory impairments by itself. Described pharmacological properties of both compounds (5 and 19) allow to give a design clue for the development of multitarget compounds with 5-HT6 (both agonist and antagonist)/AChE and/or BChE mechanism in the group of 1,3,5-triazine derivatives.
Assuntos
Doença de Alzheimer , Calcogênios , Humanos , Doença de Alzheimer/tratamento farmacológico , Serotonina , Estrutura Molecular , Relação Estrutura-Atividade , Receptores de Serotonina/metabolismo , Ligantes , Triazinas/química , Éteres , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Acetilcolinesterase/metabolismoRESUMO
1,3,4-Oxadiazole derivatives are among the most studied anticancer drugs. Previous studies have analyzed the action of different 1,3,4-oxadiazole derivatives and their effects on cancer cells. This study investigated the characterization of two new compounds named 6 and 14 on HeLa and PC-3 cancer cell lines. Based on the previously obtained IC50, cell cycle effects were monitored by flow cytometry. RNA sequencing (RNAseq) was performed to identify differentially expressed genes, followed by functional annotation using gene ontology (GO), KEGG signaling pathway enrichment, and protein-protein interaction (PPI) network analyses. The tubulin polymerization assay was used to analyze the interaction of both compounds with tubulin. The results showed that 6 and 14 strongly inhibited the proliferation of cancer cells by arresting them in the G2/M phase of the cell cycle. Transcriptome analysis showed that exposure of HeLa and PC-3 cells to the compounds caused a marked reprograming of gene expression. Functional enrichment analysis indicated that differentially expressed genes were significantly enriched throughout the cell cycle and cancer-related biological processes. Furthermore, PPI network, hub gene, and CMap analyses revealed that compounds 14 and 6 shared target genes with established microtubule inhibitors, indicating points of similarity between the two molecules and microtubule inhibitors in terms of the mechanism of action. They were also able to influence the polymerization process of tubulin, suggesting the potential of these new compounds to be used as efficient chemotherapeutic agents.
Assuntos
Antineoplásicos , Calcogênios , Neoplasias , Humanos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Relação Estrutura-Atividade , Proliferação de Células , Antineoplásicos/farmacologia , Células HeLa , Moduladores de Tubulina/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
The ability to deliver electrons is vital for dye-based photocatalysts. Conventionally, the aromatic stacking-based charge-transfer complex increases photogenerated electron accessibility but decreases the energy of excited-state dyes. To circumvent this dilemma, here we show a strategy by tuning the stacking mode of dyes. By decorating naphthalene diimide with S-bearing branches, the S···S contact-linked naphthalene diimide string is created in coordination polymer, thereby enhancing electron mobility while simultaneously preserving competent excited-state reducing power. This benefit, along with in situ assembly between naphthalene diimide strings and exogenous reagent/reactant, improves the accessibility of short-lived excited states during consecutive photon excitation, resulting in greater efficiency in photoinduced electron-transfer activation of inert bonds in comparison to other coordination polymers with different dye-stacking modes. This heterogeneous approach is successfully applied in the photoreduction of inert aryl halides and the successive formation of CAr-C/S/P/B bonds with potential pharmaceutical applications.
Assuntos
Calcogênios , Compostos Inorgânicos , Polímeros/química , Transporte de Elétrons , Naftalenos/químicaRESUMO
The conformational energy landscapes of allyl ethyl ether (AEE) and allyl ethyl sulfide (AES) were investigated using Fourier transform microwave spectroscopy in the frequency range of 5-23 GHz aided by density functional theory B3LYP-D3(BJ)/aug-cc-pVTZ calculations. The latter predicted highly competitive equilibria for both species, including 14 unique conformers of AEE and 12 for the sulfur analog AES within 14 kJ mol-1. The experimental rotational spectrum of AEE was dominated by transitions arising from its three lowest energy conformers, which differ in the arrangement of the allyl side chain, while in AES, transitions due to the two most stable forms, distinct in the orientation of the ethyl group, were observed. Splitting patterns attributed to methyl internal rotation were analyzed for AEE conformers I and II, and the corresponding V3 barriers were determined to be 12.172(55) and 12.373(32) kJ mol-1, respectively. The experimental ground state geometries of both AEE and AES were derived using the observed rotational spectra of the 13C and 34S isotopic species and are highly dependent on the electronic properties of the linking chalcogen (oxygen vs sulfur). The observed structures are consistent with a decrease in hybridization in the bridging atom from oxygen to sulfur. The molecular-level phenomena that drive the conformational preferences are rationalized through natural bond orbital and non-covalent interaction analyses. These show that interactions involving the lone pairs on the chalcogen atom with the organic side chains favor distinct geometries and energy orderings for the conformers of AEE and AES.