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G-quadruplex-guided cisplatin triggers multiple pathways in targeted chemotherapy and immunotherapy.Chemical Science Jun 2024G-quadruplexes (G4s) are atypical nucleic acid structures involved in basic human biological processes and are regulated by small molecules. To date, pyridostatin and...
G-quadruplexes (G4s) are atypical nucleic acid structures involved in basic human biological processes and are regulated by small molecules. To date, pyridostatin and its derivatives [, PyPDS (4-(2-aminoethoxy)- , -bis(4-(2-(pyrrolidin-1-yl) ethoxy) quinolin-2-yl) pyridine-2,6-dicarboxamide)] are the most widely used G4-binding small molecules and considered to have the best G4 specificity, which provides a new option for the development of cisplatin-binding DNA. By combining PyPDS with cisplatin and its analogs, we synthesize three platinum complexes, named PyPDSplatins. We found that cisplatin with PyPDS (CP) exhibits stronger specificity for covalent binding to G4 domains even in the presence of large amounts of dsDNA compared with PyPDS either extracellularly or intracellularly. Multiomics analysis reveals that CP can effectively regulate G4 functions, directly damage G4 structures, activate multiple antitumor signaling pathways, including the typical cGAS-STING pathway and AIM2-ASC pathway, trigger a strong immune response and lead to potent antitumor effects. These findings reflect that cisplatin-conjugated specific G4 targeting groups have antitumor mechanisms different from those of classic cisplatin and provide new strategies for the antitumor immunity of metals.
PubMed: 38939132
DOI: 10.1039/d4sc00643g -
Chemical Science Jun 2024Exploration of porous adsorbents with high CO/N selectivity is of great significance for reducing CO content in the atmosphere. In this study, a series of isoreticular...
Exploration of porous adsorbents with high CO/N selectivity is of great significance for reducing CO content in the atmosphere. In this study, a series of isoreticular ultramicroporous fluorinated metal-organic frameworks (MOFs) were prepared to explore the benefits of fluorinated ultramicropores in improving CO/N selectivity. Gas adsorption measurements revealed that the increase in the number of fluorine atoms in a ligand molecule leads to the increased CO uptakes and CO/N selectivity. Theoretical calculations indicate that the interaction between the fluorine atoms and adsorbed CO molecules enhances the CO-philicity, offering useful insight into the improvement of CO/N selectivity in isoreticular frameworks.
PubMed: 38939130
DOI: 10.1039/d4sc01525h -
Frontiers in Bioengineering and... 2024Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for cancer treatment due to their unique properties. Featuring high porosity, extensive surface... (Review)
Review
Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for cancer treatment due to their unique properties. Featuring high porosity, extensive surface area, chemical stability, and good biocompatibility, MOFs are ideal for efficient drug delivery, targeted therapy, and controlled release. They can be designed to target specific cellular organelles to disrupt metabolic processes in cancer cells. Additionally, functionalization with enzymes mimics their catalytic activity, enhancing photodynamic therapy and overcoming apoptosis resistance in cancer cells. The controllable and regular structure of MOFs, along with their tumor microenvironment responsiveness, make them promising nanocarriers for anticancer drugs. These carriers can effectively deliver a wide range of drugs with improved bioavailability, controlled release rate, and targeted delivery efficiency compared to alternatives. In this article, we review both experimental and computational studies focusing on the interaction between MOFs and drug, explicating the release mechanisms and stability in physiological conditions. Notably, we explore the relationship between MOF structure and its ability to damage cancer cells, elucidating why MOFs are excellent candidates for bio-applicability. By understanding the problem and exploring potential solutions, this review provides insights into the future directions for harnessing the full potential of MOFs, ultimately leading to improved therapeutic outcomes in cancer treatment.
PubMed: 38938982
DOI: 10.3389/fbioe.2024.1397804 -
Organometallics Jun 2024Rubidium and cesium are the least studied naturally occurring s-block metals in organometallic chemistry but are in plentiful supply from a sustainability viewpoint as...
Rubidium and cesium are the least studied naturally occurring s-block metals in organometallic chemistry but are in plentiful supply from a sustainability viewpoint as highlighted in the periodic table of natural elements published by the European Chemical Society. This underdevelopment reflects the phenomenal success of organometallic compounds of lithium, sodium, and potassium, but interest in heavier congeners has started to grow. Here, the synthesis and structures of rubidium and cesium bis(amido)alkyl magnesiates [(AM)MgN'alkyl], where N' is the simple heteroamide N(SiMe)(Dipp), and alkyl is Bu or CHSiMe, are reported. More stable than their Bu analogues, the reactivities of the CHSiMe magnesiates toward 1,4-cyclohexadiene are revealed. Though both reactions produce target hydrido-magnesiates [(AM)MgN'H] in crystalline form amenable to X-ray diffraction study, the cesium compound could only be formed in a trace quantity. These studies showed that the bulk of the N(SiMe)(Dipp) ligand was sufficient to restrict both compounds to dimeric structures. Bearing some resemblance to inverse crown complexes, each structure has [(AM)(N)(Mg)(N)] ring cores but differ in having no AM-N bonds, instead Rb and Cs complete the rings by engaging in multihapto interactions with Dipp π-clouds. Moreover, their hydride ions occupy μ-(AM)Mg environments, compared to μ-Mg environments in inverse crowns.
PubMed: 38938897
DOI: 10.1021/acs.organomet.4c00190 -
Organometallics Jun 2024We report the conversion of anisoles and olefins to alkenyl anisoles via a transition-metal-catalyzed arene C-H activation and olefin insertion mechanism. The catalyst...
We report the conversion of anisoles and olefins to alkenyl anisoles via a transition-metal-catalyzed arene C-H activation and olefin insertion mechanism. The catalyst precursor, [(η-CH)Rh(μ-OAc)], and the in situ oxidant Cu(OPiv) (OPiv = pivalate) convert anisoles and olefins (ethylene or propylene) to alkenyl anisoles. When ethylene is used as the olefin, the // ratio varies between approximately 1:3:1 (selective for 3-methoxystyrene) and 1:5:10 (selective for 4-methoxystyrene). When propylene is the olefin, the // regioselectivity varies between approximately 1:8:20 and 1:8.5:5. The // ratios depend on the concentration of pivalic acid and olefin. For example, when using ethylene, at relatively high pivalic acid concentrations and low ethylene concentrations, the // regioselectivity is 1:3:1. Conversely, again for use of ethylene, at relatively low pivalic acid concentrations and high ethylene concentrations, the // regioselectivity is 1:5:10. Mechanistic studies of the conversion of anisoles and olefins to alkenyl anisoles provide evidence that the regioselectivity is likely under Curtin-Hammett conditions.
PubMed: 38938896
DOI: 10.1021/acs.organomet.4c00155 -
Frontiers in Cellular and Infection... 2024and belong to the Bacteroidota phylum. Both species inhabit the oral cavity and can be associated with periodontal diseases. To survive, they must uptake heme from the...
INTRODUCTION
and belong to the Bacteroidota phylum. Both species inhabit the oral cavity and can be associated with periodontal diseases. To survive, they must uptake heme from the host as an iron and protoporphyrin IX source. Among the best-characterized heme acquisition systems identified in members of the Bacteroidota phylum is the Hmu system, with a leading role played by the hemophore-like HmuY (HmuY) protein.
METHODS
Theoretical analysis of selected HmuY proteins and spectrophotometric methods were employed to determine the heme-binding mode of the HmuY homolog (HmuY) and its ability to sequester heme. Growth phenotype and gene expression analysis of were employed to reveal the importance of the HmuY and Hmu system for this bacterium.
RESULTS
Unlike in , where HmuY uses two histidines for heme-iron coordination, other known HmuY homologs use two methionines in this process. HmuY is the first characterized representative of the HmuY family that binds heme using a histidine-methionine pair. It allows HmuY to sequester heme directly from serum albumin and HmuY, the HmuY homolog which uses two methionines for heme-iron coordination. In contrast to HmuY, which sequesters heme directly from methemoglobin, HmuY may bind heme only after the proteolytic digestion of hemoglobin.
CONCLUSIONS
We hypothesize that differences in components of the Hmu system and structure-based properties of HmuY proteins may evolved allowing different adaptations of species to the changing host environment. This may add to the superior virulence potential of over other members of the Bacteroidota phylum.
Topics: Heme; Porphyromonas gingivalis; Tannerella forsythia; Bacterial Proteins; Porphyromonas endodontalis; Humans; Gene Expression Regulation, Bacterial; Protein Binding; Iron
PubMed: 38938884
DOI: 10.3389/fcimb.2024.1421018 -
JACS Au Jun 2024Recovering precious metals from electronic waste (e-waste) using microbes presents a sustainable methodology that can contribute toward the maintenance of planetary...
Recovering precious metals from electronic waste (e-waste) using microbes presents a sustainable methodology that can contribute toward the maintenance of planetary health. To better realize the potential of bioremediation using engineered microbes, enzymes that mediate the reduction of Au(III) to Au(0) have been the subject of intense research. In this study, we report the successful engineering of a metal reductase, MerA, whose cognate substrate is mercury(II), toward other precious metals such as Au(III) and Ag(I). The engineered variant, G415I, exhibited a 15-fold increase in catalytic efficiency ( / ) in Au(III) reduction to Au(0) and a 200-fold increase in catalytic efficiency in Ag(I) reduction to Ag(0) with respect to the wild-type enzyme. The apparent shift in preference toward noncognate metal ions may be attributed to the energetics of valency preference. The improved Au(III) reductase has an apparent increased preference toward monovalent cations such as Au(I) and Ag(I), with respect to divalent cations such as Hg(II), the cognate substrate of the progenitor MerA (an increase in of 5.0-fold for Hg(II), compared to a decrease in of 5.8-fold for Au(III) and 1.8-fold for Ag(I), respectively). This study further extends the mechanistic understanding of Au(III) bioreduction that could proceed through the stabilization of Au(I) en route to Au(0) and suggests that the biosynthesis of Au nanoparticles with high efficiency can be realized through the engineering of promiscuous metal reductases for precious metal recovery from e-wastes.
PubMed: 38938813
DOI: 10.1021/jacsau.4c00297 -
JACS Au Jun 2024The counter-electrode process of an organic electrochemical reaction is integral for the success and sustainability of the process. Unlike for oxidation reactions,...
The counter-electrode process of an organic electrochemical reaction is integral for the success and sustainability of the process. Unlike for oxidation reactions, counter-electrode processes for reduction reactions remain limited, especially for deep reductions that apply very negative potentials. Herein, we report the development of a bromide-mediated silane oxidation counter-electrode process for nonaqueous electrochemical reduction reactions in undivided cells. The system is found to be suitable for replacing either sacrificial anodes or a divided cell in several reported reactions. The conditions are metal-free, use inexpensive reagents and a graphite anode, are scalable, and the byproducts are reductively stable and readily removed. We showcase the translation of a previously reported divided cell reaction to a >100 g scale in continuous flow.
PubMed: 38938809
DOI: 10.1021/jacsau.4c00186 -
JACS Au Jun 2024MeXpose is an end-to-end image analysis pipeline designed for mechanistic studies of metal exposure, providing spatial single-cell metallomics using laser...
MeXpose is an end-to-end image analysis pipeline designed for mechanistic studies of metal exposure, providing spatial single-cell metallomics using laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS). It leverages the high-resolution capabilities of low-dispersion laser ablation setups, a standardized approach to quantitative bioimaging, and the toolbox of immunohistochemistry using metal-labeled antibodies for cellular phenotyping. MeXpose uniquely unravels quantitative metal bioaccumulation (sub-fg range per cell) in phenotypically characterized tissue. Furthermore, the full scope of single-cell metallomics is offered through an extended mass range accessible by ICP-TOFMS instrumentation (covering isotopes from / 14-256). As a showcase, an human skin model exposed to cobalt chloride (CoCl) was investigated. For the first time, metal permeation was studied at single-cell resolution, showing high cobalt (Co) accumulation in the epidermis, particularly in mitotic basal cells, which correlated with DNA damage. Significant Co deposits were also observed in vascular cells, with notably lower levels in dermal fibers. MeXpose provides unprecedented insights into metal bioaccumulation with the ability to explore relationships between metal exposure and cellular responses on a single-cell level, paving the way for advanced toxicological and therapeutic studies.
PubMed: 38938797
DOI: 10.1021/jacsau.4c00154 -
Radical-Mediated α--Alkylation of Aldehydes by Consecutive 1,4- and 1,3-(Benzo)thiazolyl Migrations.JACS Au Jun 2024The direct alkylation of the α-position of aldehydes is an effective method for accessing a wide range of structurally diverse aldehydes, yet -alkylation has proven to...
The direct alkylation of the α-position of aldehydes is an effective method for accessing a wide range of structurally diverse aldehydes, yet -alkylation has proven to be a challenging task. In this study, we present a novel radical-mediated -alkylation approach targeting the α-position of aldehydes, enabling the synthesis of complex aliphatic aldehydes. The transformation is initiated by the interaction between an generated enamine intermediate and α-bromo sulfone, forming an electron donor-acceptor (EDA) complex, followed by consecutive 1,4- and 1,3-functional group migrations. This protocol operates under metal-free and mild photochemical conditions, delivering a broad scope of products and providing new mechanistic insights into radical rearrangement reactions.
PubMed: 38938795
DOI: 10.1021/jacsau.4c00322