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Bioinorganic Chemistry and Applications 2024X-ray crystallography, spectroscopy, computational methods, molecular docking studies, and DNA-binding studies have been useful in the investigations of intermolecular...
Molecular Structure, Spectroscopic, Frontier Molecular Orbital Analysis, Molecular Docking Studies, and DNA-Binding Studies of Osmium(II)-Cymene Complexes with Aryl Phosphine and Aryl Phosphonium Assemblies.
X-ray crystallography, spectroscopy, computational methods, molecular docking studies, and DNA-binding studies have been useful in the investigations of intermolecular and intramolecular interactions of osmium-cymene oxalato complexes with aryl phosphine and aryl phosphonium groups in both primary and secondary coordination spheres, respectively. Molecular structures of the novel complexes PPh[Os(--cymene)Br(--CO)] () and [Os(--cymene) (--CO)PPh] () were resolved by single-crystal X-ray diffraction (XRD). Primary and secondary coordination sphere contacts were investigated using Hirshfeld surface analysis which was supported by molecular docking (MD) studies. The MD data obtained predicted significant differences in binding energy across three receptors for the two osmium complexes. An DNA-binding study was accomplished using UV-Vis spectroscopy which showed that both and bond with DNA through an intercalation approach. The optimized molecular geometry, frontier molecular orbital (E and E) energies, global electrophilicity index (), chemical hardness (), chemical potential (), and the energy band gap (E-E) were calculated utilizing density functional theory (DFT) methods. Computed structural parameters (bond lengths and angles) support the experimental single-crystal XRD data.
PubMed: 38840845
DOI: 10.1155/2024/6697523 -
Science Advances Jun 2024α-Chiral alkyl phosphines are privileged structural motifs with a wide application in organic and medical synthesis. It is highly desirable to develop stereoselective...
α-Chiral alkyl phosphines are privileged structural motifs with a wide application in organic and medical synthesis. It is highly desirable to develop stereoselective methods to prepare these enantioenriched molecules. The incorporation of C()─H functionalization and chiral phosphine chemistry is much less explored, probably because of the weak reactivity of C()─H bonds and/or the challenging site- and stereoselectivity issues. Herein, we disclose a synergistic catalysis system to enable an enantioselective radical addition process of α-substituted vinylphosphine oxides. An array of diverse α-chiral alkyl phosphors compounds is smoothly accessed by using the readily available chemicals as the inert C()─H bond reagent, such as sulfides, amines, alkenes, and toluene derivatives, exerting remarkable chemo-, site-, and enantioselectivity. On the basis of the mechanistic studies, both the C()─H bond activation and the stereochemistry-determining step are proposed to involve a single-electron transfer/proton transfer process.
PubMed: 38838147
DOI: 10.1126/sciadv.adn9738 -
PloS One 2024Poisoning is a significant public health problem globally. Ethiopia is a low-income country undergoing technological and social change that may increase access to drugs... (Observational Study)
Observational Study
BACKGROUND
Poisoning is a significant public health problem globally. Ethiopia is a low-income country undergoing technological and social change that may increase access to drugs and chemicals, potentially increasing the incidence of poisoning. This study describes the epidemiology of hospital admissions due to poisoning in a region of Ethiopia.
METHODS
An institution based prospective observational study was employed, as a study design, in selected hospitals of the region from January to December 2018.
RESULTS
Of 442 poisoning cases, 78 (17.6%) died. Almost all poisoning cases were intentional self-poisonings. The most frequent poisonings were organophosphate compounds, 145 (32.8%), and metal phosphides (majorly aluminum phosphide), 115 (26.0%). The ingested poison was most frequently accessed from the patients' homes, 243 (55.0%), followed by purchases from local shops, 159 (36%). The median duration of admission was 24 hours. Of all the cases, 23 (5.2%) were admitted to intensive care units (ICU) requiring mechanical ventilation. Most of the cases admitted to the ICU were aluminum phosphide-poisoned patients. The majority of deaths (43 of 78) were due to metal phosphides. From the multivariate logistic regression analysis, altered level of consciousness on hospital arrival, metal phosphide poisoning, and no laboratory result as a part of the diagnosis process or investigation of the extent of toxicity were found to be significantly associated with the likelihood of poor treatment outcome.
CONCLUSION
The majority of the poisoning cases were females. The most common reasons for the intent of self-poisoning were dispute-related, mainly family disharmonies, followed by psychiatric conditions. The poisoning agents were mostly obtained from households. Organophosphate compounds and metal phosphides were the first and the second most frequently encountered poisoning agents, respectively, and it was noted that the later ones were responsible for most of the fatal cases. Of the pharmacologic interventions, atropine was the only agent regarded as an antidote. The most commonly employed agent for supportive treatment was cimetidine followed by maintenance fluids, while gastric lavage was the only GI decontamination method used among others. The fatality rate of poisoning in this study was found to be much higher than in other similar studies. Impaired consciousness upon hospital arrival, metal phosphide poisoning, and no involvement of laboratory investigation were found to significantly associate with the likelihood of death. Generally, the results dictate the need for the design and implementation of strategies to create awareness, prevent, and manage poisoning incidences in the community.
Topics: Humans; Ethiopia; Female; Male; Adult; Prospective Studies; Middle Aged; Poisoning; Adolescent; Young Adult; Phosphines; Hospitalization; Child; Aged; Aluminum Compounds; Intensive Care Units; Hospitals; Child, Preschool
PubMed: 38820326
DOI: 10.1371/journal.pone.0303438 -
Accounts of Chemical Research Jun 2024ConspectusAromatic esters are cost-effective, versatile, and commonly used scaffolds that are readily synthesized or encountered as synthetic intermediates. While most...
ConspectusAromatic esters are cost-effective, versatile, and commonly used scaffolds that are readily synthesized or encountered as synthetic intermediates. While most conventional reactions involving these esters are nucleophilic acyl substitutions or 1,2-nucleophilic additions─where a nucleophile attacks the carbonyl group, decarbonylative transformations offer an alternative pathway by using the carbonyl group as a leaving group. This transition-metal-catalyzed process typically begins with oxidative addition of the C(acyl)-O bond to the metal. Subsequently, the reaction involves the migration of CO to the metal center, the reaction with a nucleophile, and reductive elimination to yield the final product. Pioneering work by Yamamoto on nickel complexes and the development of decarbonylative reactions (such as Mizoroki-Heck-type olefination) using aromatic carboxylic anhydrides catalyzed by palladium were conducted by de Vries and Stephan. Furthermore, reports have surfaced of decarbonylative hydrogenation of pyridyl methyl esters by Murai using ruthenium catalysts as well as Mizoroki-Heck-type reactions of nitro phenyl esters by Gooßen under palladium catalysis. Our group has been at the forefront of developing decarbonylative C-H arylations of phenyl esters with 1,3-azoles and aryl boronic acids using nickel catalysts. The key to this reaction is the use of phenyl esters, which are easy to synthesize, stabilize, and handle, allowing oxidative addition of the C(acyl)-O bond; nickel, which facilitates oxidative addition of the C(acyl)-O bond; and suitable bidentate phosphine ligands that can stabilize the intermediate. By modification of the nucleophiles, esters have been effectively utilized as electrophiles in cross-coupling reactions, encouraging the development of these nucleophiles among researchers. This Account summarizes our advancements in nucleophile development for decarbonylative coupling reactions, particularly highlighting the utilization of aromatic esters in diverse reactions such as alkenylation, intramolecular etherification, α-arylation of ketones, C-H arylation, methylation, and intramolecular C-H arylation for dibenzofuran synthesis, along with cyanation and reductive coupling. We also delve into reaction types that are distinct from typical decarbonylative reactions, including ester dance reactions, aromatic ring exchanges, and deoxygenative transformations, by focusing on the oxidative addition of the C(acyl)-O bond of the aromatic esters to the metal complex. For example, the ester dance reaction is hypothesized to undergo 1,2-translocation starting with oxidative addition to a palladium complex, leading to a sequence of -deprotonation/decarbonylation, followed by protonation, carbonylation, and reductive elimination. The aromatic exchange reaction likely involves oxidative addition of complexes of different aryl electrophiles with a nickel complex. In deoxygenative coupling, an oxidative addition complex with palladium engages with a nucleophile, forming an acyl intermediate that undergoes reductive elimination in the presence of an appropriate reducing agent. These methodologies are poised to captivate the interest of synthetic chemists by offering unconventional and emerging approaches for transforming aromatic esters. Moreover, we demonstrated the potential to transform readily available basic chemicals into new compounds through organic synthesis.
PubMed: 38819671
DOI: 10.1021/acs.accounts.4c00233 -
JACS Au May 2024How different is carbon compared to other elements in the periodic table? Can carbon compounds be regarded as coordination complexes with carbon as the central element... (Review)
Review
How different is carbon compared to other elements in the periodic table? Can carbon compounds be regarded as coordination complexes with carbon as the central element undergoing a facile exchange of its ligands? Although carbon clearly plays a special role among the elements of the periodic table, recent studies have drawn parallels between the bonding situation and the reactivity of carbon compounds to transition metal complexes. This Perspective summarizes recent reports about ylidic and zwitterionic compounds that were shown to exhibit ambiguous bonding situations that can be interpreted as donor-acceptor interactions similar to the bond between a metal and a neutral ligand. Based on this conception, ligand exchange reactions prototypical of transition metal complexes were realized at carbon atoms, enabling new synthetic strategies for the synthesis of reactive species and building blocks. In particular, the exchange of N, CO, and phosphine ligands led to the development of a mild method for accessing new compounds and reagents with unusual properties, such as vinylidene ketenes or stable ketenyl anions, that open up a diverse but still poorly explored follow-up chemistry.
PubMed: 38818072
DOI: 10.1021/jacsau.4c00112 -
Nature Communications May 2024Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a...
Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a formidable task owing to their intrinsic high reactivity. Herein we report straightforward synthesis, characterization and reactivity studies of a phosphanorcaradiene, in which one of the benzene rings in the flanking fluorenyl substituents is intramolecularly dearomatized through attachment to the phosphorus atom. It is facilely obtained by the reduction of phosphorus(III) dichloride precursor with potassium graphite. Despite being thermally robust, it acts as a synthetic equivalent of a transient phosphinidene. It reacts with trimethylphosphine and isonitrile to yield phosphanylidene-phosphorane and 1-phospha-3-azaallene, respectively. When it is treated with one and two molar equivalents of azide, iminophosphane and bis(imino)phosphane are isolated, respectively. Moreover, it is capable of activating ethylene and alkyne to afford [1 + 2] cycloaddition products, as well as oxidative cleavage of Si-H and N-H bonds to yield secondary phosphines. All the reactions proceed smoothly at room temperature without the presence of transition metals. The driving force for these reactions is most likely the high ring-constraint of the three-membered PC ring and recovery of the aromaticity of the benzene ring.
PubMed: 38811584
DOI: 10.1038/s41467-024-49042-1 -
European Journal of Medicinal Chemistry Aug 2024Herein, we present a comprehensive review focusing on synthetic strategies, detailed structural analysis, and anticancer activity investigations of complexes following... (Review)
Review
Herein, we present a comprehensive review focusing on synthetic strategies, detailed structural analysis, and anticancer activity investigations of complexes following the general formula [LM(μ-diphosphine)M'L] where M = group 8 metal; M' = any transition metal; μ-diphosphine = bridging ligand; L and L = ligand spheres). Both homo- and heteromultimetallic complexes will be discussed in detail. We review in vitro, in vivo and in silico anticancer activity investigations, in an attempt to draw comparisons between the various complexes and derive structure-activity relationships (SAR). This review solely focuses on complexes falling under the general formula stated above that have been studied for their anticancer activities, other complexes falling into that scheme but which have not undergone anticancer testing are not included in this review. We compare the anticancer activities of these complexes to their mononuclear counterparts, and a positive control (cisplatin) when possible and present a summary of all existing data to date and attempt to draw some conclusions on the future development of these complexes.
Topics: Antineoplastic Agents; Humans; Ligands; Phosphines; Coordination Complexes; Transition Elements; Structure-Activity Relationship; Drug Screening Assays, Antitumor; Molecular Structure; Animals; Cell Proliferation
PubMed: 38805938
DOI: 10.1016/j.ejmech.2024.116528 -
Dalton Transactions (Cambridge, England... Jun 2024Group 4 Lewis acids are well-known catalysts and precursors for (non-aqueous) sol-gel chemistry. Titanium, zirconium and hafnium halides, and alkoxy halides are...
Group 4 Lewis acids are well-known catalysts and precursors for (non-aqueous) sol-gel chemistry. Titanium, zirconium and hafnium halides, and alkoxy halides are precursors for the controlled synthesis of nanocrystals, often in the presence of Lewis base. Here, we investigate the interaction of Lewis bases with the tetrahalides (MX, X = Cl, Br) and metal alkoxy halides (MX(OR), = 1-3, R = OPr, OBu). The tetrahalides yield the expected Lewis acid-base adducts MXL (L = tetrahydrofuran or phosphine oxide). The mixed alkoxy halides react with Lewis bases in a more complex way. P NMR spectroscopy reveals that excess of phosphine oxide yields predominantly the complexation product, while a (sub)stoichiometric amount of phosphine oxide causes disproportionation of the MX(OR) species into MX(OR) and MX(OR). The combination of complexation and disproportionation yields an atypical Job plot. In the case of zirconium isopropoxy chlorides, we fitted the concentration of all observed species and extracted thermodynamic descriptors from the Job plot. The complexation equilibrium constant decreases in the series: ZrCl(OPr) > ZrCl(OPr) ≫ ZrCl(OPr), while the disproportionation equilibrium constant follows the opposite trend. Using calculations at the DFT level of theory, we show that disproportionation is driven by the more energetically favorable Lewis acid-base complex formed with the more acidic species. We also gain more insight into the isomerism of the complexes. The disproportionation reaction turns out to be a general phenomenon, for titanium, zirconium and hafnium, for chlorides and bromides, and for isopropoxides and -butoxides.
PubMed: 38805233
DOI: 10.1039/d4dt01299b -
Cancer Cell International May 2024Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior,...
PURPOSE
Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD.
METHODS
PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis.
RESULTS
Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP.
CONCLUSIONS
This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD.
PubMed: 38802854
DOI: 10.1186/s12935-024-03374-6 -
Cureus Apr 2024Aluminum phosphide (ALP) poisoning poses a significant public health concern worldwide, with a high mortality rate and no established definitive treatment. This case...
Aluminum phosphide (ALP) poisoning poses a significant public health concern worldwide, with a high mortality rate and no established definitive treatment. This case report highlights a 30-year-old male with G6PD deficiency who ingested ALP tablets, presenting with jaundice and anemia. Despite the severity of ALP poisoning, the concurrent G6PD deficiency appeared to confer a protective effect, potentially mitigating complications. Laboratory investigations revealed characteristic findings, including unconjugated hyperbilirubinemia and normocytic hypochromic anemia. Treatment involved supportive measures and transfusion, leading to clinical improvement and discharge. The discussion focuses on the pathophysiology of G6PD deficiency and its protective role against ALP poisoning, supported by a literature review and experimental evidence. Moreover, potential therapeutic interventions targeting oxidative stress are discussed. This case underscores the importance of considering G6PD deficiency in ALP poisoning management and highlights avenues for further research into protective mechanisms and treatment strategies.
PubMed: 38800224
DOI: 10.7759/cureus.58888