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Topics in Current Chemistry (Cham) Apr 2017The phosphoryl group, PO, is the dynamic structural unit in the biological chemistry of phosphorus. Its transfer from a donor to an acceptor atom, with oxygen much more... (Review)
Review
The phosphoryl group, PO, is the dynamic structural unit in the biological chemistry of phosphorus. Its transfer from a donor to an acceptor atom, with oxygen much more prevalent than nitrogen, carbon, or sulfur, is at the core of a great majority of enzyme-catalyzed reactions involving phosphate esters, anhydrides, amidates, and phosphorothioates. The serendipitous discovery that the phosphoryl group could be labeled by "nuclear mutation," by substitution of PO by MgF or AlF, has underpinned the application of metal fluoride (MF ) complexes to mimic transition states for enzymatic phosphoryl transfer reactions, with sufficient stability for experimental analysis. Protein crystallography in the solid state and F NMR in solution have enabled direct observation of ternary and quaternary protein complexes embracing MF transition state models with precision. These studies have underpinned a radically new mechanistic approach to enzyme catalysis for a huge range of phosphoryl transfer processes, as varied as kinases, phosphatases, phosphomutases, and phosphohydrolases. The results, without exception, have endorsed trigonal bipyramidal geometry (tbp) for concerted, "in-line" stereochemistry of phosphoryl transfer. QM computations have established the validity of tbp MF complexes as reliable models for true transition states, delivering similar bond lengths, coordination to essential metal ions, and virtually identical hydrogen bond networks. The emergence of protein control of reactant orbital overlap between bond-forming species within enzyme transition states is a new challenging theme for wider exploration.
Topics: Aluminum Compounds; Fluorides; Magnesium Compounds; Molecular Structure; Phosphines; Phosphoric Monoester Hydrolases; Phosphotransferases; Phosphotransferases (Phosphomutases)
PubMed: 28299727
DOI: 10.1007/s41061-017-0130-y -
PloS One 2018Phosphine is the only general use fumigant for the protection of stored grain, though its long-term utility is threatened by the emergence of highly phosphine-resistant...
Phosphine is the only general use fumigant for the protection of stored grain, though its long-term utility is threatened by the emergence of highly phosphine-resistant pests. Given this precarious situation, it is essential to identify factors, such as stress preconditioning, that interfere with the efficacy of phosphine fumigation. We used Caenorhabditis elegans as a model organism to test the effect of pre-exposure to heat and cold shock, UV and gamma irradiation on phosphine potency. Heat shock significantly increased tolerance to phosphine by 3-fold in wild-type nematodes, a process that was dependent on the master regulator of the heat shock response, HSF-1. Heat shock did not, however, increase the resistance of a strain carrying the phosphine resistance mutation, dld-1(wr4), and cold shock did not alter the response to phosphine of either strain. Pretreatment with the LD50 of UV (18 J cm-2) did not alter phosphine tolerance in wild-type nematodes, but the LD50 (33 J cm-2) of the phosphine resistant strain (dld-1(wr4)) doubled the level of resistance. In addition, exposure to a mild dose of gamma radiation (200 Gy) elevated the phosphine tolerance by ~2-fold in both strains.
Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Cold Temperature; Fumigation; Gamma Rays; Gases; Hot Temperature; Mutation; Phosphines; Stress, Physiological; Ultraviolet Rays
PubMed: 29672544
DOI: 10.1371/journal.pone.0195349 -
European Journal of Medicinal Chemistry Oct 2020Herein, we review developments in synthesis, structure, and biological (anti-cancer) activities of 1,1-bis(diphenylphosphino)methane (dppm) bridged homo- and... (Review)
Review
Herein, we review developments in synthesis, structure, and biological (anti-cancer) activities of 1,1-bis(diphenylphosphino)methane (dppm) bridged homo- and heterobimetallic systems of the type LM(μ-dppm)M'L (M and M' are transition metals which may be different or the same and L are co-ligands) since the first such reported bimetallic system in 1987 until the present time (2020). As the simplest diphosphine, dppm enables facile formation of bimetallic complexes, where, given the short spacer between the PPh groups, close spatial proximity of the metal centres is ensured. We concentrate on complexes bearing no M-M interaction and contrast biological activities of these complexes with mononuclear counterparts and positive control agents such as cisplatin, in an attempt to elucidate patterns in the biological activities of these complexes.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Coordination Complexes; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Ligands; Metals; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phosphines; Salmonella typhimurium; Spectrophotometry, Ultraviolet; Staphylococcus aureus; Structure-Activity Relationship
PubMed: 32784095
DOI: 10.1016/j.ejmech.2020.112613 -
Molecules (Basel, Switzerland) Nov 2012The Kabachnik-Fields (phospha-Mannich) reaction involving the condensation of primary or secondary amines, oxo compounds (aldehydes and ketones) and >P(O)H species,... (Review)
Review
The Kabachnik-Fields (phospha-Mannich) reaction involving the condensation of primary or secondary amines, oxo compounds (aldehydes and ketones) and >P(O)H species, especially dialkyl phosphites, represents a good choice for the synthesis of α-aminophosphonates that are of significant importance due to their biological activity. In general, these three-component reactions may take place via an imine or an α-hydroxy-phosphonate intermediate. The monitoring of a few Kabachnik-Fields reactions by in situ Fourier transform IR spectroscopy has indicated the involvement of the imine intermediate that was also justified by theoretical calculations. The Kabachnik-Fields reaction was extended to >P(O)H species, comprising cyclic phosphites, acyclic and cyclic H-phosphinates, as well as secondary phosphine oxides. On the other hand, heterocyclic amines were also used to prepare new α-amino phosphonic, phosphinic and phosphine oxide derivatives. In most cases, the synthesis under solvent-free microwave (MW) conditions is the method of choice. It was proved that, in the cases studied by us, there was no need for the use of any catalyst. Moreover, it can be said that sophisticated and environmentally unfriendly catalysts suggested are completely unnecessary under MW conditions. Finally, the double Kabachnik-Fields reaction has made available bis(phosphonomethyl)amines, bis(phosphinoxidomethyl)amines and related species. The bis(phosphinoxidomethyl)amines serve as precursors for bisphosphines that furnish ring platinum complexes on reaction with dichlorodibenzonitriloplatinum.
Topics: Animals; Drug Carriers; Humans; Hydrogen Bonding; Microwaves; Models, Chemical; Organophosphonates; Phosphines; Schiff Bases; Thermodynamics
PubMed: 23117425
DOI: 10.3390/molecules171112821 -
Angewandte Chemie (International Ed. in... Apr 2021Polyalkyl furans are widespread in nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the...
Polyalkyl furans are widespread in nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the construction of tetraalkyl furans remains non-trivial. The prevalence of alkyl groups in bioactive furan natural products, combined with the desirable bioactivities of tetraalkyl furans, calls for a general synthetic protocol for polyalkyl furans. This paper describes a Michael-Heck approach, using sequential phosphine-palladium catalysis, for the preparation of various polyalkyl furans from readily available precursors. The versatility of this method is illustrated by the total syntheses of nine distinct polyalkylated furan natural products belonging to different classes, namely the furanoterpenes rosefuran, sesquirosefuran, and mikanifuran; the marine natural products plakorsins A, B, and D and plakorsin D methyl ester; and the furan fatty acids 3D5 and hydromumiamicin.
Topics: Biological Products; Catalysis; Furans; Molecular Structure; Organometallic Compounds; Palladium; Phosphines
PubMed: 33533120
DOI: 10.1002/anie.202015232 -
Molecules (Basel, Switzerland) Apr 2020In an effort to explain the experimentally observed variation of the photocatalytic activity of t Bu 3 P, n Bu 3 P and (MeO) 3 P in the blue-light regime [Helmecke et...
In an effort to explain the experimentally observed variation of the photocatalytic activity of t Bu 3 P, n Bu 3 P and (MeO) 3 P in the blue-light regime [Helmecke et al., Org. Lett. 21 (2019) 7823], we have explored the absorption characteristics of several phosphine- and phosphite-IC 4 F 9 adducts by means of relativistic density functional theory and multireference configuration interaction methods. Based on the results of these computational and complementary experimental studies, we offer an explanation for the broad tailing of the absorption of t Bu 3 P-IC 4 F 9 and (MeO) 3 P-IC 4 F 9 into the visible-light region. Larger coordinate displacements of the ground and excited singlet potential energy wells in n Bu 3 P-IC 4 F 9 , in particular with regard to the P-I-C bending angle, reduce the Franck-Condon factors and thus the absorption probability compared to t Bu 3 P-IC 4 F 9 . Spectroscopic and computational evaluation of conformationally flexible and locked phosphites suggests that the reactivity of (MeO) 3 P may be the result of oxygen lone-pair participation and concomitant broadening of absorption. The proposed mechanism for the phosphine-catalyzed homolytic C-I cleavage of perfluorobutane iodide involves S ← S absorption of the adduct followed by intersystem crossing to the photochemically active T 1 state.
Topics: Algorithms; Iodides; Light; Models, Theoretical; Molecular Conformation; Phosphines; Photochemical Processes; Quantum Theory; Spectrum Analysis
PubMed: 32244568
DOI: 10.3390/molecules25071606 -
Organic Letters Jun 2021Decarbonylative Sonogashira cross-coupling of carboxylic acids by palladium catalysis is presented. The carboxylic acid is activated in situ by the formation of a mixed...
Decarbonylative Sonogashira cross-coupling of carboxylic acids by palladium catalysis is presented. The carboxylic acid is activated in situ by the formation of a mixed anhydride and further decarbonylates using the Pd(OAc)/Xantphos system to provide an aryl-Pd intermediate, which is intercepted by alkynes to access the traditional Pd(0)/(II) cycle using carboxylic acids as ubiquitous and orthogonal electrophilic cross-coupling partners. The methodology efficiently constructs new C(sp)-C(sp) bonds and can be applied to the derivatization of pharmaceuticals. Mechanistic studies give support to decarbonylation preceding transmetalation in this process.
Topics: Alkynes; Anhydrides; Carboxylic Acids; Catalysis; Molecular Structure; Palladium; Phosphines; Xanthenes
PubMed: 34096312
DOI: 10.1021/acs.orglett.1c01445 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2022The fine-tuning of metal-phosphine-catalyzed reactions relies largely on accessing ever more precisely tuned phosphine ligands by de-novo synthesis. Late-stage C-H...
The fine-tuning of metal-phosphine-catalyzed reactions relies largely on accessing ever more precisely tuned phosphine ligands by de-novo synthesis. Late-stage C-H functionalization and diversification of commercial phosphines offers rapid access to entire libraries of derivatives based on privileged scaffolds. But existing routes, relying on phosphorus-directed transformations, only yield functionalization of C -H bonds in a specific position relative to phosphorus. In contrast to phosphorus-directed strategies, herein we disclose an orthogonal functionalization strategy capable of introducing a range of substituents into previously inaccessible positions on arylphosphines. The strongly coordinating phosphine group acts solely as a bystander in the sterically controlled borylation of bulky phosphines, and the resulting borylated phosphines serve as the supporting ligands for palladium during diversification through phosphine self-assisted Suzuki-Miyaura reactions.
Topics: Catalysis; Ligands; Palladium; Phosphines; Phosphorus
PubMed: 35789048
DOI: 10.1002/chem.202202074 -
Journal of the American Chemical Society Dec 2018We report a Pd-catalyzed intermolecular hydrophosphinylation of 1,3-dienes to afford chiral allylic phosphine oxides. Commodity dienes and air stable phosphine oxides...
We report a Pd-catalyzed intermolecular hydrophosphinylation of 1,3-dienes to afford chiral allylic phosphine oxides. Commodity dienes and air stable phosphine oxides couple to generate organophosphorus building blocks with high enantio- and regiocontrol. This method constitutes the first asymmetric hydrophosphinylation of dienes.
Topics: Alkadienes; Allyl Compounds; Catalysis; Chemistry Techniques, Synthetic; Coordination Complexes; Palladium; Phosphines; Stereoisomerism
PubMed: 30451496
DOI: 10.1021/jacs.8b11150 -
Chimia 2016The secondary phosphine oxides are known to exist in equilibrium between the pentavalent phosphine oxides (SPO) and the trivalent phosphinous acids (PA). This... (Review)
Review
The secondary phosphine oxides are known to exist in equilibrium between the pentavalent phosphine oxides (SPO) and the trivalent phosphinous acids (PA). This equilibrium can be displaced in favour of the trivalent tautomeric form upon coordination to late transition metals. This tutorial review provides the state of the art of the use of secondary phosphine oxides as pre-ligands in transition metal-catalysed reactions. Using a combination of SPOs and several metals such as Pd, Pt, Ru, Rh and Au, a series of effective and original transformations have been obtained and will be discussed here.
Topics: Catalysis; Ligands; Metals; Models, Molecular; Oxides; Phosphines
PubMed: 26931212
DOI: 10.2533/chimia.2016.8