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ChemMedChem Jun 2022A phosphine gold(I) and phosphine-phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed...
A phosphine gold(I) and phosphine-phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked in vitro thanks to two-photon imaging. Their in vitro and in vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor-bearing BALB/c mice. They displayed moderate to strong antiproliferative properties and the phosphine-phosphonium gold(I) complex induced significant in vivo anti-cancer effect.
Topics: Animals; Antineoplastic Agents; Gold; Mice; Neoplasms; Phosphines
PubMed: 35254001
DOI: 10.1002/cmdc.202100773 -
Journal of Medicinal Chemistry Mar 2020Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic...
Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic compounds have been found to be beneficial against various medical ailments but have yet to be applied to fungal infections. Here, we explore the activity of linear and square-planar gold(I)-phosphine complexes against a panel of 28 fungal strains including spp., spp., spp., and spp. Notably, two square-planar gold(I) complexes with excellent broad-spectrum activity display potent antifungal effects against strains of , an emerging multidrug-resistant fungus that presents a serious global health threat. To characterize the biological activity of these gold(I) complexes, we used a series of time-kill studies, cytotoxicity and hemolysis assays, as well as whole-cell uptake and development of resistance studies.
Topics: Antifungal Agents; Coordination Complexes; Fungi; Gold; Humans; Microbial Sensitivity Tests; Models, Molecular; Mycoses; Phosphines
PubMed: 31841324
DOI: 10.1021/acs.jmedchem.9b01436 -
Journal of the American Chemical Society Sep 2022Template-directed synthesis of nucleic acids in the polymerase chain reaction is based on the use of a primer, which is elongated in the replication process. The...
Template-directed synthesis of nucleic acids in the polymerase chain reaction is based on the use of a primer, which is elongated in the replication process. The attachment of a high affinity primer to the end of a template chain has been implemented for templating the synthesis of triazole oligomers. A covalent ester base-pair was used to attach a primer to a mixed sequence template. The resulting primed template has phenol recognition units on the template, which can form noncovalent base-pairs with phosphine oxide monomers via H-bonding, and an alkyne group on the primer, which can react with the azide group on a phosphine oxide monomer. Competition reactions between azides bearing phosphine oxide and phenol recognition groups were used to demonstrate a substantial template effect, due to H-bonding interactions between the phenols on the template and phosphine oxides on the azide. The largest rate acceleration was observed when a phosphine oxide 2-mer was used, because this compound binds to the template with a higher affinity than compounds that can only make one H-bond. The P NMR spectrum of the product duplex shows that the H-bonds responsible for the template effect are present in the product, and this result indicates that the covalent ester base-pairs and noncovalent H-bonded base-pairs developed here are geometrically compatible. Following the templated reaction, it is possible to regenerate the template and liberate the copy strand by hydrolysis of the ester base-pair used to attach the primer, thus completing a formal replication cycle.
Topics: Alkynes; Azides; Esters; Nucleic Acids; Oxides; Phenol; Phosphines; Templates, Genetic; Triazoles
PubMed: 36082527
DOI: 10.1021/jacs.2c08119 -
International Journal of Molecular... May 2021Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the...
Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate -Leu--nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Leucine aminopeptidase) and barley seeds (HvLAP, Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.
Topics: Animals; Enzyme Inhibitors; Leucyl Aminopeptidase; Models, Molecular; Peptide Fragments; Phosphines; Protein Conformation; Swine
PubMed: 34065004
DOI: 10.3390/ijms22105090 -
Analytical and Bioanalytical Chemistry Oct 2022
Topics: Phosphines; Zinc Compounds
PubMed: 36117197
DOI: 10.1007/s00216-022-04195-0 -
Angewandte Chemie (International Ed. in... May 2020Bacterial phosphothreonine lyases, or phospholyases, catalyze a unique post-translational modification that introduces dehydrobutyrine (Dhb) or dehydroalanine (Dha) in...
Bacterial phosphothreonine lyases, or phospholyases, catalyze a unique post-translational modification that introduces dehydrobutyrine (Dhb) or dehydroalanine (Dha) in place of phosphothreonine or phosphoserine residues, respectively. We report the use of a phospha-Michael reaction to label proteins and peptides modified with Dha or Dhb. We demonstrate that a nucleophilic phosphine probe is able to modify Dhb-containing proteins and peptides that were recalcitrant to reaction with thiol or amine nucleophiles under mild aqueous conditions. Furthermore, we used this reaction to detect multiple Dhb-modified proteins in mammalian cell lysates, including histone H3, a previously unknown target of phospholyases. This method should prove useful for identifying new phospholyase targets, profiling the biomarkers of bacterial infection, and developing enzyme-mediated strategies for bioorthogonal labeling in living cells.
Topics: Alanine; Amines; Aminobutyrates; Bacteria; Bacterial Infections; Biomarkers; Histones; Humans; Lyases; Phosphines; Phosphothreonine; Protein Processing, Post-Translational; Sulfhydryl Compounds
PubMed: 32196905
DOI: 10.1002/anie.202003631 -
Astrobiology Oct 2021The possibility of life in the venusian clouds was proposed in the 1960s, and recently this hypothesis has been revived with the potential detection of phosphine (PH) in...
The possibility of life in the venusian clouds was proposed in the 1960s, and recently this hypothesis has been revived with the potential detection of phosphine (PH) in Venus' atmosphere. These observations may have detected ∼5-20 ppb phosphine on Venus (Greaves , 2020), which raises questions about venusian atmospheric/geochemical processes and suggests that this phosphine could possibly be generated by biological processes. In such a claim, it is essential to understand the abiotic phosphorus chemistry that may occur under Venus-relevant conditions, particularly those processes that may result in phosphine generation. Here, we discuss two related abiotic routes for phosphine generation within the atmosphere of Venus. Based on our assessment, corrosion of large impactors as they ablate near Venus' cloud layer, and the presence of reduced phosphorus compounds in the subcloud layer could result in production of phosphine and may explain the phosphine detected in Venus' atmosphere or on other rocky planets. We end on a cautionary note: although there may be life in the clouds of Venus, the detection of a simple, single gas, phosphine, is likely not a decisive indicator.
Topics: Extraterrestrial Environment; Phosphines; Planets; Venus
PubMed: 34551269
DOI: 10.1089/ast.2021.0034 -
Organic & Biomolecular Chemistry Oct 2021A new method for the synthesis of 3-oxoisoindolin-1-ylphosphine oxides bearing same or different substituents on the phosphorus atom is described. The one-pot...
A new method for the synthesis of 3-oxoisoindolin-1-ylphosphine oxides bearing same or different substituents on the phosphorus atom is described. The one-pot three-component reaction of 2-formylbenzoic acid, primary amines and achiral or P-stereogenic secondary phosphine oxides provided the target compounds under catalyst-free, mild conditions and for short reaction times. The deoxygenation of a 3-oxoisoindolin-1-ylphosphine oxide was also studied, and the phosphine obtained could be converted to a sulphide and to a platinum complex. The crystal structures of a selected phosphine oxide and the corresponding platinum species were investigated by X-ray diffraction analysis. The biological activity, such as cytotoxicity on different cell lines and antibacterial activity of the 3-oxoisoindolin-1-ylphosphine oxides was also investigated. Based on the IC values obtained, several derivatives showed moderate activity against the HL-60 cell line and two compounds containing 3,5-dimethylphenyl groups on the phosphorus atom showed promising activity against bacteria.
Topics: Phosphines
PubMed: 34581392
DOI: 10.1039/d1ob01610e -
Clinica Chimica Acta; International... Sep 2021Aluminum phosphide (AlP) is a popular fumigant used widely for the safe storage of food grain. Although A1P is free from toxic residues, it releases phosphine which acts... (Review)
Review
Aluminum phosphide (AlP) is a popular fumigant used widely for the safe storage of food grain. Although A1P is free from toxic residues, it releases phosphine which acts on mitochondrial components of almost all types of pests. Unfortunately A1P is also a common suicidal agent in developing countries with no known antidote. In addition, accidental exposure to phosphine may also occur. AlP poisoning affects cardiac and vascular tissue directly and can result in multiorgan system failure leading to death in severe cases. There is no specific biomarker for diagnosing AlP poisoning and management depends on a high level of clinical suspicion. Although acetylcholinesterase has been suggested as a surrogate biomarker of AlP exposure, there are opposing views. In this review, we analyzed the relevant published material with emphasis on the need to recognize and explore the use of plasma mitochondrial enzyme activity as a potential biomarker for AlP exposure.
Topics: Aluminum Compounds; Humans; Pesticides; Phosphines
PubMed: 34077754
DOI: 10.1016/j.cca.2021.05.026 -
Chemical Reviews Jul 2020A critically important process in catalysis is the formation of an active catalyst from the combination of a metal precursor and a ligand, as the efficacy of this... (Review)
Review
A critically important process in catalysis is the formation of an active catalyst from the combination of a metal precursor and a ligand, as the efficacy of this reaction governs the amount of active catalyst. This Review is a comprehensive overview of reactions catalyzed by nickel and an added bidentate phosphine, focusing on the steps transforming the combination of precatalyst and ligand into an active catalyst and the potential effects of this transformation on nickel catalysis. Reactions covered include common cross-coupling reactions, such as Suzuki, Heck, Kumada, and Negishi couplings, addition reactions, cycloadditions, C-H functionalizations, polymerizations, hydrogenations, and reductive couplings, among others. Overall, the most widely used nickel precatalyst with free bidentate phosphines is Ni(cod), which accounts for ∼50% of the reports surveyed, distantly followed by Ni(acac) and Ni(OAc), which account for ∼10% each. By compiling the reports of these reactions, we have calculated statistics of the usage and efficacy of each ligand with Ni(cod) and other nickel sources. The most common bidentate phosphines are simple, relatively inexpensive ligands, such as DPPE, DCPE, DPPP, and DPPB, along with others with more complex backbones, such as DPPF and Xantphos. The use of expensive chiral phosphines is more scattered, but the most common ligands include BINAP, Me-Duphos, Josiphos, and related analogs.
Topics: Alkadienes; Catalysis; Ligands; Molecular Structure; Nickel; Organometallic Compounds; Phosphines
PubMed: 32491839
DOI: 10.1021/acs.chemrev.9b00682