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Pharmaceutics May 2024Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in... (Review)
Review
Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of At-labeled compounds. The preclinical and clinical applications of At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of At production and quality control methods, and the continued evaluation of At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of At-based targeted alpha therapy. With the growing interest and investment in this field, At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.
PubMed: 38931860
DOI: 10.3390/pharmaceutics16060738 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution... (Review)
Review
Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution of hereditary and behavioral factors, such as nutritional inadequacy, along with the influences of environment and reduced physical activity. Two types of adipose tissue widely known are white and brown. While white adipose tissue functions predominantly as a key energy storage, brown adipose tissue has a greater mass of mitochondria and expresses the uncoupling protein 1 () gene, which allows thermogenesis and rapid catabolism. Even though white and brown adipocytes are of different origin, activation of the brown adipocyte differentiation program in white adipose tissue cells forces them to transdifferentiate into "beige" adipocytes, characterized by thermogenesis and intensive lipolysis. Nowadays, researchers in the field of small molecule medicinal chemistry and gene therapy are making efforts to develop new drugs that effectively overcome insulin resistance and counteract obesity. Here, we discuss various aspects of white-to-beige conversion, adipose tissue catabolic re-activation, and non-shivering thermogenesis.
PubMed: 38931457
DOI: 10.3390/ph17060790 -
Molecules (Basel, Switzerland) Jun 2024In the published publication [...].
In the published publication [...].
PubMed: 38931013
DOI: 10.3390/molecules29122926 -
Molecules (Basel, Switzerland) Jun 2024(1) Background: In the quest to accurately model the radiolysis of water in its supercritical state, a detailed understanding of water's molecular structure,...
(1) Background: In the quest to accurately model the radiolysis of water in its supercritical state, a detailed understanding of water's molecular structure, particularly how water molecules are arranged in this unique state, is essential. (2) Methods: We conducted molecular dynamics simulations using the SPC/E water model to investigate the molecular structures of supercritical water (SCW) over a wide temperature range, extending up to 800 °C. (3) Results: Our results show that at a constant pressure of 25 MPa, the average intermolecular distance around a reference water molecule remains remarkably stable at ~2.9 Å. This uniformity persists across a substantial temperature range, demonstrating the unique heterogeneous nature of SCW under these extreme conditions. Notably, the simulations also reveal intricate patterns within SCW, indicating the simultaneous presence of regions with high and low density. As temperatures increase, we observe a rise in the formation of molecular clusters, which are accompanied by a reduction in their average size. (4) Conclusions: These findings highlight the necessity of incorporating the molecular complexity of SCW into traditional track-structure chemistry models to improve predictions of SCW behavior under ionizing radiation. The study establishes a foundational reference for further exploration of the properties of supercritical water, particularly for its application in advanced nuclear technologies, including the next generation of water-cooled reactors and their small modular reactor variants that utilize SCW as a coolant.
PubMed: 38931011
DOI: 10.3390/molecules29122947 -
Molecules (Basel, Switzerland) Jun 2024The tetradentate ligand, merging a carbazole unit with high triplet energy and dimethoxy bipyridine, renowned for its exceptional quantum efficiency in coordination with...
The tetradentate ligand, merging a carbazole unit with high triplet energy and dimethoxy bipyridine, renowned for its exceptional quantum efficiency in coordination with metals like Pt, is expected to demonstrate remarkable luminescent properties. However, instances of tetradentate ligands such as bipyridine-based pyridylcarbazole derivatives remain exceptionally scarce in the current literature. In this study, we developed a tetradentate ligand based on carbazole and 2,3'-bipyridine and successfully complexed it with Pt(II) ions. This novel compound () serves as a sky-blue phosphorescent material for use in light-emitting diodes. Based on single-crystal X-ray analysis, compound has a distorted square-planar geometry with a 5/6/6 backbone around the Pt(II) core. Bright sky-blue emissions were observed at 488 and 516 nm with photoluminescent quantum yields of 34% and a luminescent lifetime of 2.6 μs. TD-DFT calculations for revealed that the electronic transition was mostly attributed to the ligand-centered (LC) charge transfer transition with a small contribution from the metal-to-ligand charge transfer transition (MLCT, ~14%). A phosphorescent organic light-emitting device was successfully fabricated using this material as a dopant, along with 3'-di(9H-carbazol-9-yl)-1,1'-biphenyl (mCBP) and 9-(3'-carbazol-9-yl-5-cyano-biphenyl-3-yl)-9H-carbazole-3-carbonitrile (CNmCBPCN) as mixed hosts. A maximum quantum efficiency of 5.2% and a current efficiency of 15.5 cd/A were obtained at a doping level of 5%.
PubMed: 38930994
DOI: 10.3390/molecules29122929 -
Molecules (Basel, Switzerland) Jun 2024In-depth insights into the oligomers of carbon dots (CDs) prepared from small-molecule precursors are important in the study of the carbonization mechanism of CDs and...
In-depth insights into the oligomers of carbon dots (CDs) prepared from small-molecule precursors are important in the study of the carbonization mechanism of CDs and for our knowledge of their complex structure. Herein, citric acid (CA) and ethylenediamine (EDA) were used as small-molecule precursors to prepare CDs in an aqueous solution. The structure of oligomers acquired from CA and EDA in different molar ratios and their formation process were first studied using density functional theory, including the dispersion correction (DFT-D3) method. The results showed that the energy barrier of dimer cyclization was higher than that of its linear polymerization, but the free energy of the cyclized product was much lower than that of its reactant, and IPCA (5-oxo-1,-2,3,5-tetrahydroimidazo [1,2-a]pyridine-7-carboxylic acid) could therefore be obtained under certain conditions. The oligomers obtained from different molar ratios of EDA and CA were molecular clusters formed by short polyamide chains through intermolecular forces; with the exception of when the molar ratio of EDA to CA was 0.5, excessive CA did not undergo an amidation reaction but rather attained molecular clusters directly through intermolecular forces. These oligomers exhibited significant differences in their surface functional groups, which would affect the carbonization process and the surface structure of CDs.
PubMed: 38930988
DOI: 10.3390/molecules29122920 -
Molecules (Basel, Switzerland) Jun 2024Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by... (Review)
Review
Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by amphiphilic solutes. This comprehensive review explores state-of-the-art techniques for characterizing microemulsions, which are versatile solutions essential across various industries, such as pharmaceuticals, food, and petroleum. This article delves into spectroscopic methods, nuclear magnetic resonance, small-angle scattering, dynamic light scattering, conductometry, zeta potential analysis, cryo-electron microscopy, refractive index measurement, and differential scanning calorimetry, examining each technique's strengths, limitations, and potential applications. Emphasizing the necessity of a multi-technique approach for a thorough understanding, it underscores the importance of integrating diverse analytical methods to unravel microemulsion structures from molecular to macroscopic scales. This synthesis provides a roadmap for researchers and practitioners, fostering advancements in microemulsion science and its wide-ranging industrial applications.
PubMed: 38930964
DOI: 10.3390/molecules29122901 -
Molecules (Basel, Switzerland) Jun 2024The CRISPR-Cas9 system has emerged as the most prevalent gene editing technology due to its simplicity, high efficiency, and low cost. However, the homology-directed...
The CRISPR-Cas9 system has emerged as the most prevalent gene editing technology due to its simplicity, high efficiency, and low cost. However, the homology-directed repair (HDR)-mediated gene knock-in in this system suffers from low efficiency, which limits its application in animal model preparation, gene therapy, and agricultural genetic improvement. Here, we report the design and optimization of a simple and efficient reporter-based assay to visualize and quantify HDR efficiency. Through random screening of a small molecule compound library, two groups of compounds, including the topoisomerase inhibitors and PIM1 kinase inhibitors, have been identified to promote HDR. Two representative compounds, etoposide and quercetagetin, also significantly enhance the efficiency of CRISPR-Cas9 and HDR-mediated gene knock-in in mouse embryos. Our study not only provides an assay to screen compounds that may facilitate HDR but also identifies useful tool compounds to facilitate the construction of genetically modified animal models with the CRISPR-Cas9 system.
Topics: Gene Editing; CRISPR-Cas Systems; Proto-Oncogene Proteins c-pim-1; Animals; Mice; Protein Kinase Inhibitors; Topoisomerase Inhibitors; Humans; Recombinational DNA Repair; Gene Knock-In Techniques
PubMed: 38930955
DOI: 10.3390/molecules29122890 -
Molecules (Basel, Switzerland) Jun 2024The complex and variable structure of subsurface oil reservoirs as well as the small pore throat size of reservoirs make it extremely important to investigate the effect...
The complex and variable structure of subsurface oil reservoirs as well as the small pore throat size of reservoirs make it extremely important to investigate the effect of oil-water-rock interactions for enhancing oil recovery. In this paper, the powder wettability of oil sand with different polar solvents was investigated using the improved Washburn capillary rise method, and the surface free energy of oil sand was calculated in combination with the OWRK method. In addition, the wettability of anionic surfactants HABS and PS solutions on the surface of oil sand was determined, and it showed that their wetting rates showed different trends after CMC (critical micelle concentration). The C×cosθ value of HABS decreased significantly with increasing concentration, whereas PS showed little changes. This may be related to the aggregate structure formed by HABS on the oil sand surface. Meanwhile, the interfacial free energy between crude oil and oil sand was obtained by crude oil-to-oil sand wetting experiments, and found that the wetting rate of crude oil to oil sand was much lower than that of solvents and surfactants. In combination with the above results and the oil-water interfacial tension (IFT), the oil-water-rock three-phase contact angle and the work of adhesion between the crude oil and the solid were obtained by Young's equation. From the three-phase contact angle results, it can be found that the contact angle values of both HABS and PS are obviously higher than that of the simulated water, and both HABS and PS have the ability to significantly reduce the work of adhesion, which shows a strong ability to strip the oil film on the surface of the solid. The research results of this paper are helpful to understand the oil displacement mechanism of chemical flooding in reservoir pores, which is of great significance for improving oil recovery.
PubMed: 38930943
DOI: 10.3390/molecules29122878 -
Molecules (Basel, Switzerland) Jun 2024In the field of human health research, the homeostasis of copper (Cu) is receiving increased attention due to its connection to pathological conditions, including... (Review)
Review
In the field of human health research, the homeostasis of copper (Cu) is receiving increased attention due to its connection to pathological conditions, including diabetes mellitus (DM). Recent studies have demonstrated that proteins associated with Cu homeostasis, such as ATOX1, FDX1, ATP7A, ATPB, SLC31A1, p53, and UPS, also contribute to DM. Cuproptosis, characterized by Cu homeostasis dysregulation and Cu overload, has been found to cause the oligomerization of lipoylated proteins in mitochondria, loss of iron-sulfur protein, depletion of glutathione, production of reactive oxygen species, and cell death. Further research into how cuproptosis affects DM is essential to uncover its mechanism of action and identify effective interventions. In this article, we review the molecular mechanism of Cu homeostasis and the role of cuproptosis in the pathogenesis of DM. The study of small-molecule drugs that affect these proteins offers the possibility of moving from symptomatic treatment to treating the underlying causes of DM.
Topics: Humans; Diabetes Mellitus; Copper; Homeostasis; Drug Design; Animals; Small Molecule Libraries; Mitochondria; Reactive Oxygen Species
PubMed: 38930917
DOI: 10.3390/molecules29122852