Phosphonium Research Articles

Magnetic biochar/quaternary phosphonium salt reduced antibiotic resistome and pathobiome on pakchoi leaves

Antibiotic resistance genes (ARGs) and human pathogenic bacteria (HPB) in leafy vegetable is a matter of concern as they can be transferred from soil, atmosphere, and foliar sprays, and poses a potential risk to public health. While traditional disinfection technologies are effective in reducing the presence of ARGs and HPB in soil. A new technology, foliar spraying with magnetic biochar/quaternary ammonium salt (MBQ), was demonstrated and applied to the leaf surface. High-throughput quantitative PCR targeting 96 valid ARGs and 16 S rRNA sequencing were used to assess its efficacy in reducing ARGs and HPB. The results showed that spraying MBQ reduced 97.0 ± 0.81% of “high-risk ARGs”, associated with seven classes of antibiotic resistance in pakchoi leaves within two weeks. Water washing could further reduce “high-risk ARGs” from pakchoi leaves by 19.8%− 24.6%. The relative abundance of HPB closely related to numerous ARGs was reduced by 15.2 ± 0.23% with MBQ application. Overall, this study identified the potential risk of ARGs from leafy vegetables and clarified the significant implications of MBQ application for human health as it offers a promising strategy for reducing ARGs and HPB in leafy vegetables.

Photocatalytic 1,2-Phosphorus-Migrative [3 + 2] Cycloaddition of Tri(t-butyl)phosphine with Terminal Alkynes.

Tri(t-butyl)phosphine and terminal alkynes undergo 1,2-phosphorus-migrative [3 + 2] cycloaddition in the presence of a proton source under photocatalytic conditions. The reaction exhibits broad functional group tolerance and affords substituted cyclic phosphonium salts, which are amenable to further derivatization by Wittig olefination. Theoretical studies suggest that the phosphorus 1,2-migration of a β-phosphonioalkyl radical proceeds through a phosphine radical cation-alkene complex as a pseudointermediate, and the two fragments in the intermediate are bound to each other through multiple noncovalent interactions.

Visible-Light Photocatalytic Synthesis of Difluoromethylated Selenides from Selenosulfonates through a Radical Process.

A photocatalytic synthesis of difluoromethylated selenides from selenosulfonates is described here. Bench-stable difluoromethyl phosphonium salt [Ph3PCF2H]Br reacts smoothly with selenosulfonates to give a series of functionalized difluoromethylated selenides in moderate to good yields via a radical process. This protocol is free of a stoichiometric base and reductant, has tolerance of functional groups, and has successful late-stage modification of bioactive molecules, which provides facile access to molecules of pharmaceutical relevance.

Charge Transfer Complex-Enabled Synthesis of (Hetero)arylated m-Carboranes from m-Carborane Phosphonium Salts.

A photoinduced charge transfer complex (CTC)-enabled photoreduction of carborane phosphonium salts for the cage carbon (hetero)arylation of carboranes was developed. It offers a convenient approach for introducing a wide range of aryl and heteroaryl groups, such as pyrroles, thiophenes, indoles, thianaphthenes, benzofurans, pyridines, and benzenes, into carboranes. This strategy offers operational simplicity, mild reaction conditions, and a broad substrate scope, making it highly advantageous.

Assessing mitochondria-targeted acyl hydroquinones on the mitochondrial platelet function and cytotoxic activity: Role of the linker length

IntroductionThe use of triphenylphosphonium cation (TPP+) linked to phenolic compounds by alkyl chains has a significant relevance as a mitochondrial delivery strategy in biomedicine because it affects mitochondrial bioenergetics in models of noncommunicable diseases such as cancer and cardiovascular-related conditions. Studies indicate that a long alkyl chain (10–12 carbon) increases the mitochondrial accumulation of TPP+-linked drugs. In contrast, other studies show that these compounds are consistently toxic to micromolar concentrations (as observed in platelets). In the present study, we evaluated the in vitro effect of three series of triphenylphosphonium-linked acyl hydroquinones derivates on the metabolism and function of human platelets using 3–9 carbons for the alkyl linker. Those were assessed to determine the role of the length of the alkyl chain linker on platelet toxicity. MethodsHuman platelets were exposed in vitro to different concentrations (2–40 μM) of every compound; cellular viability, phosphatidylserine exposition, mitochondrial membrane potential (ΔΨm), intracellular calcium release, and intracellular ROS generation were assessed by flow cytometry. An in silico energetic profile was generated with Umbrella sampling molecular dynamics (MD). Results and conclusionsThere was an increase in cytotoxic activity directly related to the length of the acyl chain and lipophilicity, as seen by three techniques, and this was consistent with a decrease in ΔΨm. The in silico energetic profiles point out that the permeability of the mitochondrial membrane may be involved in the cytotoxicity of phosphonium salts. This information may be relevant for the design of new TPP+ -based drugs with a safe cardiovascular profile.

Deep Eutectic Solvents: Green Applications

Recently, ionic liquids (ILs) have attracted considerable attention in scientific research as greensolvents. Owing to their low vapor pressure, ILs were qualified as green solvents. However, the ”greenaffiliation” of ILs is now contested by many research groups. The hazardous toxicity and the very poorbiodegradability of many ILs have been reported in the literature. Additionally, their synthesis generallyrequires a large amount of salts and solvents. These drawbacks and the high price of common ILs delayedtheir industrial applications. To overcome these drawbacks, a new generation of solvents, named DeepEutectic Solvents (DESs), has emerged. DESs can be formed by mixing, at moderate temperature, two ormore components that can be chosen to be cheap, renewable and biodegradable. These compounds arecapable of forming a eutectic mixture with a melting point lower than that of the individual component.DESs are generally liquid at temperatures lower than 100 C.Many DESs have similar physical-chemical properties to those of ILs, while being much cheaper andenvironmentally friendlier. Owing to these advantages, there is growing interest in DESs in many fields ofresearch. DESs are chemically tailorable solvents since they can be designed by properly combining variousquaternary ammonium or phosphonium salts with different hydrogen bond donors (HBD) or complexingagents. Hence, task-specific DESs with different physical-chemical properties can be prepared.In this work, we discuss the important contributions of DESs in diverse applications, e.g. electrochemicalprocesses, catalysis, synthesis, absorption of CO2, desulfurization of fuels, separation, and dissolution andextraction processes.

Design and Application of Peptide‐Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis

AbstractChiral phosphonium salt catalysis, traditionally classified as a type of phase transfer catalysis, has proven to be a powerful strategy for the stereoselective preparation of diverse optically active molecules. However, there still remain numerous forbidding issues of reactivity and selectivity in such well‐known organocatalysis system. Accordingly, the development of new and high‐performance phosphonium salt catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes the prominent endeavours in the development of a new family of chiral peptide‐mimic phosphonium salt catalysts with multiple hydrogen‐bonding donors and their applications in a plethora of enantioselective synthesis during the past few years. Hopefully, this minireview will pave a way for further developing much more efficient and privileged chiral ligands/catalysts featuring exclusively catalytic ability in asymmetric synthesis.

Design and Application of Peptide-Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis.

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer catalysis, has proven to be a powerful strategy for the stereoselective preparation of diverse optically active molecules. However, there still remain numerous forbidding issues of reactivity and selectivity in such well-known organocatalysis system. Accordingly, the development of new and high-performance phosphonium salt catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes the prominent endeavours in the development of a new family of chiral peptide-mimic phosphonium salt catalysts with multiple hydrogen-bonding donors and their applications in a plethora of enantioselective synthesis during the past few years. Hopefully, this minireview will pave a way for further developing much more efficient and privileged chiral ligands/catalysts featuring exclusively catalytic ability in asymmetric synthesis.

Modular synthesis of unsymmetric 1,3-diphosphinopropanes through sequential substitution reactions

Methods to synthesize diphosphines with different substituents on the two phosphorus centers are limited, particularly for the synthesis of unsymmetric bis(dialkylphosphine) ligands. Herein is reported a modular and high-yielding synthesis of borane-protected unsymmetric 1,3-bis(diphosphino)propanes containing either two dialkylphosphine moieties or one dialkylphosphine and one diphenylphosphine group. The method relies on sequential phosphine substitution on 1,3-dibromopropane. The borane-protected diphosphines are readily converted to bis(phosphonium salts), which serve as convenient preligands. Palladium(II) complexes of di-tert-butyl(3-(dicyclohexylphosphino)propyl)phosphine (tBuCyPP), di-tert-butyl(3-(diisobutylphosphino)propyl)phosphine (tBuiBuPP), and diisobutyl((3-(dicyclohexylphosphino)propyl)phosphine (CyiBuPP) have been prepared. The tBuiBuPP and CyiBuPP complexes have been structurally characterized and their structural properties compared to symmetric (1,3-diphosphinopropane)palladium dichloride structures.

A New Class of Donor‐π‐Acceptor Phosphonium Salt Exhibiting Intriguing Thermally Activated Delayed Fluorescence

AbstractThermally activated delayed fluorescence (TADF) behaviors in metal halide perovskite and perovskite derivatives are rarely reported due to the absence of suitable TADF molecules that can serve as the A‐site cations. Herein, a series of novel donor‐π‐acceptor type of molecules are developed by adopting substituted phosphine and phosphonium as the electron donor and acceptor linked by the polarized π‐spacer. The prepared ((diphenylphosphaneyl)phenyl)diphenylphosphonium‐X (BzDPP‐X, X = counterions: Cl−, Br−, I−, NO3−, CH3COO− etc.) salts show bright emission in the visible range with TADF characteristics due to the strong intramolecular charge transfer (ICT). Benefiting from the spatially separated highest occupied molecular orbital and lowest unoccupied molecular orbital, small singlet‐triplet energy splitting (ΔEST) is obtained, facilitating the reverse intersystem crossing process. It turns out that the emission of BzDPP‐X is dependent on the counter anions, and the counterions help to stabilize the ICT state. Intriguingly, the emission can be tuned by integrating metal‐halide units into the above phosphonium salt. Remarkably, the zinc‐based halide exhibits a higher photoluminescence quantum yield (36.2%) than the pure benzyl(2‐(diphenylphosphaneyl)phenyl)diphenylphosphonium bromide (26.9%). This work exemplifies an easy design concept and a facile synthetic method toward ionic luminescent materials.

Discovery of a phosphonium ionic liquid phase from the reaction of trialkylphosphines and epichlorohydrin carbonate and application as a CO2-based triphasic demulsifier of crude oil

In the search for a cyclic carbonate-based compound with amphiphilic properties, we combined highly polar epichlorohydrin carbonate with a long chain trialkylphosphine (P(Octyl)3). Under prolonged stirring, these mutually insoluble reagents led to the formation of a single phase containing several phosphonium salts whose composition and mechanism of formation has been systematically investigated by a combination of NMR techniques. Importantly, the obtained phase was immiscible with both water and hydrocarbons and had an intermediate density between such phases thus enabling its application as a unique triphasic demulsifier for water in oil (W/O) mixtures using actual crude oil. This work led to a new insight into the chemistry of CO2-made cyclic carbonates and to their application as intermediates and components of CO2-dervied demulsifiers.

Visible light-induced thiocyanation of gem-difluorinated phosphonium salts

gem-Difluorinated phosphonium salts were generated from nitrones by methylation and reaction with (triphenylphosphonio)difluoroacetate. The phosphonium salts were subjected to visible light-induced phosphonium–thiocyanate exchange in the presence of ammonium thiocyanate, copper thiocyanate, and an iridium photocatalyst. The sequence of the reactions was performed in one pot affording thiocyanates attached to the difluoromethylene fragment.

Effect of Divalent Cations and Other Ions on the Tetrahydrofuran Crystal Inhibition of Quaternary Ammonium Salts-Relevance to the Efficiency of Gas Hydrate Quaternary Anti-agglomerants.

Gas hydrate anti-agglomerants (AAs) are a class of low-dosage hydrate inhibitor that are used to prevent plugging of gas hydrates in oil and condensate upstream flow lines. Industrial AAs are mostly cationic surfactants which are "hydrate-philic", i.e., they are designed to interact with and modify gas hydrate crystal growth. Tetrahydrofuran (THF) hydrate crystal growth studies have been used for many years to determine useful functional groups to incorporate into AA surfactants. In particular, quaternary ammonium and phosphonium salts with optimized alkyl groups show good THF crystal growth inhibition, which is a key property for AAs. AAs are often screened and tested in model brines containing sodium chloride despite the produced water containing various divalent cations. Recent studies have shown that AAs performed better when tested in brines containing both sodium and calcium ions rather than just sodium ions. Here, we present THF hydrate crystal growth studies on quaternary ammonium and phosphonium salts and other related molecules including guanidinium salts and amine oxides. Tests were carried out with a variety of cations including sodium, calcium, magnesium, and lithium at identical pre-determined subcooling, in order to investigate the effect of the ion size and charge density on the crystal growth inhibition. We also investigate the effect of using the more polarizable iodide ions compared to chloride ions. Our results show that crystal growth inhibition in solutions with calcium ions is somewhat greater than that with sodium ions, in agreement with past studies on the effect of AA performance with mono- and divalent cations. However, the variation does not seem to be primarily related to the charge density and polarizing ability of the cations. This study therefore provides evidence that AAs should be tested in brines containing all the ions present in the produced water and not just sodium chloride brine.

Polybenzoxazine bearing phosphonium and phenol functions catalyzed the cycloaddition of CO2 into epoxide reactions

Polybenzoxazine bearing phosphonium and phenol functions was firstly designed, synthesized, and evaluated for the cycloaddition of CO2 into epoxide (CCE) reactions. Benzoxazine monomers intrinsically installed with phosphonium halide moiety were thermally polymerized to obtain phenolic-type polybenzoxazines. The bifunctional polybenzoxazine catalyst promoted CCE reactions at 120 °C within 2 h to afford high yields up to 96% under atmospheric pressure. The catalyst was recycled four times and maintained 92% yield. A possible bifunctional catalytic mechanism composed of hydrogen-bonding activation by phenol and co-catalysis by halide was proposed and validated. The easy preparation of the benzoxazine monomers with variety of catalytic moieties, and one-step fabrication of the polybenzoxazines suggest untapped potential of manifold polymeric catalyst design and applications.

Cover Picture: Visible‐Light‐Induced Photoreduction of Carborane Phosphonium Salts: Efficient Synthesis of Carborane‐Oxindole‐Pharmaceutical Hybrids (Angew. Chem. Int. Ed. 31/2023)

Cover Picture: Visible‐Light‐Induced Photoreduction of Carborane Phosphonium Salts: Efficient Synthesis of Carborane‐Oxindole‐Pharmaceutical Hybrids (Angew. Chem. Int. Ed. 31/2023)

Titelbild: Visible‐Light‐Induced Photoreduction of Carborane Phosphonium Salts: Efficient Synthesis of Carborane‐Oxindole‐Pharmaceutical Hybrids (Angew. Chem. 31/2023)

Titelbild: Visible‐Light‐Induced Photoreduction of Carborane Phosphonium Salts: Efficient Synthesis of Carborane‐Oxindole‐Pharmaceutical Hybrids (Angew. Chem. 31/2023)

Outstanding Performance of the Deep Eutectic Solvent-Based Aqueous Biphasic System Constructed with Sodium Citrate for a Green Gold Separation.

Aqueous biphasic systems (ABSs) that are based on deep eutectic solvents (DESs) are environmentally benign systems to use for metal ion separation. In this work, a series of DESs was synthesized for the first time with PEG 400 as hydrogen bond donors and tetrabutylphonium bromide (P4Br), tetrabutylammonium bromide (N4Br), or tetrabutylammonium chloride (N4Cl) as hydrogen bond acceptors, and then they were combined with citrate (Na3C6H5O7), which is eco-friendly, to construct an ABS for use in the separation of Au(I) from an aurocyanide solution. Phase diagrams of DESs + Na3C6H5O7 + H2O systems were constructed using the experimentally measured data. Multiple factors that affect the efficiency of the gold extraction were studied; these factors were the species of salt or DES and their content, the equilibrium pH, the oscillation time, and the initial gold concentration. Gold(I) is preferentially retained in the DES-rich phase, and the P4Br:PEG 1:2 + Na3C6H5O7 + H2O system has a high extraction efficiency of 100.0% under optimized conditions. FT-IR, NMR, and TEM characterizations and DFT calculations show that the migration of Au(I) from the salt-rich to the DES-rich phase follows an ion exchange mechanism. Specifically, Au(CN)2- replaces Br- in the original P4Br and generates a stable ion pair with the quaternary phosphonium salt cation, P+, and this replacement is driven by electrostatic attractions. A new strong hydrogen bond network simultaneously forms between the anionic Au(CN)2- and the -OH group in the PEG 400 component. Finally, the gold of Au(I)-loaded P4Br:PEG 1:2 can be successfully reduced by sodium borohydride with an efficiency of 100.0%. The strategy to extract gold(I) from alkaline cyanide solutions using an ABS based on DESs as proposed in this work provides a potential platform for developing green technology for recovering gold.

MEPicides: α,β-unsaturated Fosmidomycin N-Acyl Analogs as Efficient Inhibitors of Plasmodium falciparum 1-Deoxy-d-xylulose-5-phosphate reductoisomerase.

Malaria, a mosquito-borne disease caused by several parasites of the Plasmodium genus, remains a huge threat to global public health. There are an estimated 0.5 million malaria deaths each year, mostly among African children. Unlike humans, Plasmodium parasites and a number of important pathogenic bacteria employ the methyl erythritol phosphate (MEP) pathway for isoprenoid synthesis. Thus, the MEP pathway represents a promising set of drug targets for antimalarial and antibacterial compounds. Here, we present new unsaturated MEPicide inhibitors of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of the MEP pathway. A number of these compounds have demonstrated robust inhibition of Plasmodium falciparum DXR, potent antiparasitic activity, and low cytotoxicity against HepG2 cells. Parasites treated with active compounds are rescued by isopentenyl pyrophosphate, the product of the MEP pathway. With higher levels of DXR substrate, parasites acquire resistance to active compounds. These results further confirm the on-target inhibition of DXR in parasites by the inhibitors. Stability in mouse liver microsomes is high for the phosphonate salts, but remains a challenge for the prodrugs. Taken together, the potent activity and on-target mechanism of action of this series further validate DXR as an antimalarial drug target and the α,β-unsaturation moiety as an important structural component.

Electron Donor‐Acceptor Complex Initiated Photochemical Phosphorus Arylation with Diaryliodonium Salts toward the Synthesis of Phosphine Oxides

AbstractArylation of amino‐, diamino‐ and triaminophosphines with aryl(mesityl)iodonium triflates under blue light irradiation followed by oxidative P−N bond cleavage in the in situ generated amino phosphonium salts under hydrolytic conditions represent a method for the synthesis of substituted arylphosphine oxides, arylphosphinic and arylphosphonic amides respectively. The proposed approach is based on using visible light as the only promoter for the C−P bond formation, accommodates a variety of functional groups, and can be applied to the late‐stage C−H functionalization of drug molecules.

Aerobic Coupling of Organophosphonium Salts with Alkenes: Catalyst‐Free C(sp3)−C(sp2) Bond Formation

AbstractAn aerobic coupling of benzhydryl phosphonium salts with simple alkenes for accessing trisubstituted olefins is developed under metal‐free, catalyst‐free, and additive‐free conditions. New C(sp3)−C(sp2) bond is constructed via the C−P and C−H bond functionalization by synergistically using O2 as a “green” oxidant and DMSO as a promoter. The method also distinguishes itself by its broad substrate scope and synthetic potential. Particularly, the use of 1,3,5‐trimethoxybenzene fragment in the resulting products as a carbon‐based leaving group for further transformations is proved to be feasible.