Bis-phosphonium Salts Research Articles

Bisphosphonium salt catalyzed [3 + 2] annulation of N-tosylimino(iso)quinolinium ylides with aryl olefins under blue LED irradiation

A visible-light-induced [3 + 2] annulation of N-tosylimino(iso)quinolinium ylides with aryl olefins, catalyzed by a bisphosphonium salt has been developed. Furthermore, the synthesis method of the bisphosphonium salts was improved.

Synthesis, structure and antimicrobial activity of sterically hindered bis-phosphonium derivatives of 2,6-di-tert-butyl-4-methylphenol

New biologically active quaternary bis-phosphonium salts were obtained by quaternization of 4-bromomethyl-2,6-di-tert-butylphenol with several α,ω,-bis(diphenylphosphino)-alkanes. All synthesized compounds demonstrated high antibacterial and antifungal activities against pathogenic microflora of humans and animals.

Bis(amidophenolato)phosphonium: Si-H Hydride Abstraction and Phosphorus-Ligand Cooperative Activation of C-C Multiple Bonds.

The first bis(amidophenolato)phosphonium salts are prepared and fully characterized. The perfluorinated derivative represents the strongest monocationic phosphorus Lewis acid on the fluoride and hydride ion affinity scale isolable to date. This affinity enables new reactions, such as hydride abstraction from Et3 SiH, the first phosphaalkoxylation of an alkyne or a phosphorus catalyzed intramolecular hydroarylation. All properties and reactions are scrutinized by theory and experiment. Substantial σ- and π-acidity provides the required affinity for substrate activation, while phosphorus-ligand cooperativity substantially enriches the reactivity portfolio of phosphonium ions.

Metal-Free Cationic Polymerization of Vinyl Ethers with Strict Temporal Control by Employing an Organophotocatalyst.

By virtue of spatiotemporal control over the chain propagating, visible-light-regulated organocatalytic photoredox cationic polymerization provides an appealing approach for the construction of metal-free, well-defined polymers and materials. However, so far, organic photocatalysts capable of mediated cationic polymerization of vinyl ethers are quite limited, and the photocontrol or efficiency is often eroded due to the difficulty in achieving a good activation-deactivation balance, which is greatly dependent on the redox property of the catalyst. Here, we introduce a new type of organic photocatalysts, bisphosphonium salts, which show high performance in the photoregulated reversible addition-fragmentation chain transfer cationic polymerization of vinyl ethers and allow the synthesis of poly(vinyl ethers) with predictable molecular weights and narrow dispersities at low ppm catalyst loadings under visible light. In particular, the tunable redox potential and excellent stability endow the bisphosphonium salts strict temporal control, thus enabling the metal-free polymerization with a halt in a long dark period.

Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria. Within the mitochondria, the Succinate Dehydrogenase complex (SDH) was investigated as a target for bisphosphonium salts, but while its subunit 1 (SDH1) was present at low levels in the bloodstream form trypanosomes, the assembled complex was hardly detectable. RNAi knockdown of the SDH1 subunit produced no growth phenotype, either in bloodstream or in the procyclic (insect) forms and we conclude that in trypanosomes SDH is not the target for bisphosphonium salts. Instead, the compounds inhibited ATP production in intact mitochondria, as well as the purified F1 ATPase, to a level that was similar to 1 mM azide. Co-incubation with azide and bisphosphonium compounds did not inhibit ATPase activity more than either product alone. The results show that, in T. brucei, bisphosphonium compounds do not principally act on succinate dehydrogenase but on the mitochondrial FoF1 ATPase.

One-Pot Synthesis of 1,3-Bis(phosphinomethyl)arene PCP/PNP Pincer Ligands and Their Nickel Complexes

A one-pot synthesis of arene-based PCP/PNP ligands has been developed. The reaction of 1,3-bis(bromomethyl)benzene or 2,6-bis(bromomethyl)pyridine with various chlorophosphines in acetonitrile afforded bis-phosphonium salts. These salts can then be reduced by magnesium powder to yield PCP or PNP ligands. In comparison to traditional synthetic methods for making PCP/PNP ligands involving the use of secondary phosphines, this new alternative method allows for the use of chlorophosphines, which are cheaper, safer to handle, and have a broader range of commercially available derivatives. This is especially true for the chlorophosphines with less bulky alkyl groups. Moreover, the one-pot procedure can be extended to allow for the direct synthesis of PCP/PNP nickel complexes. By using nickel powder as the reductant, the resulting nickel halide was found to directly undergo metalation with the PCP or PNP ligand to generate nickel complexes in high yields.

New Derivatives of Pyridoxine Exhibit High Antibacterial Activity against Biofilm-EmbeddedStaphylococcusCells

Opportunistic bacteria Staphylococcus aureus and Staphylococcus epidermidis often form rigid biofilms on tissues and inorganic surfaces. In the biofilm bacterial cells are embedded in a self-produced polysaccharide matrix and thereby are inaccessible to biocides, antibiotics, or host immune system. Here we show the antibacterial activity of newly synthesized cationic biocides, the quaternary ammonium, and bisphosphonium salts of pyridoxine (vitamin B6) against biofilm-embedded Staphylococci. The derivatives of 6-hydroxymethylpyridoxine were ineffective against biofilm-embedded S. aureus and S. epidermidis at concentrations up to 64 μg/mL, although all compounds tested exhibited low MICs (2 μg/mL) against planktonic cells. In contrast, the quaternary ammonium salt of pyridoxine (N,N-dimethyl-N-((2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methyl)octadecan-1-aminium chloride (3)) demonstrated high biocidal activity against both planktonic and biofilm-embedded bacteria. Thus, the complete death of biofilm-embedded S. aureus and S. epidermidis cells was obtained at concentrations of 64 and 16 μg/mL, respectively. We suggest that the quaternary ammonium salts of pyridoxine are perspective to design new synthetic antibiotics and disinfectants for external application against biofilm-embedded cells.

Bis-phosphonium salts of pyridoxine: The relationship between structure and antibacterial activity

A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr>Et>Me. Further increasing of length and branching of alkyl chain leads to the reduction of antibacterial activity. Replacement of the phenyl substituents at the phosphorus atoms in 5,6-bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]-dioxino[4,5-c]pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl as well as chloride anions in the compound 1 with bromides (compound 14a) increased the activity against Staphylococcus aureus and Staphylococcus epidermidis up to 5times (MICs=1–1.25μg/ml). But in practically all cases chemical modifications of compound 1 led to the increase of its toxicity for HEK-293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which demonstrated lower MIC values against S. aureus and S. epidermidis (1μg/ml) and lower cytotoxicity on HEK-293 cells (CC50=200μg/ml). Compound 10a had no significant mutagenic and genotoxic effects and was selected for further evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine were much more toxic than vancomycin.

Synthesis and structures of non-cyclic and cyclic mono- and bisphosphonium salts derived from 1,8-bis(diphenylphosphino)naphthalene

A monoalkylated 1,8-bis(diphenylphosphino)naphthalene (dppn) was prepared by treating diphosphine with 1,8-bis(bromomethyl)naphthalene. Unprecedented cyclizations of monophosphonium salts in polar solvents, such as DMF or acetonitrile were elucidated. The mechanistic pathway of the cyclization reaction was postulated and X-ray crystal structure analyses of the resulting 2,2-diphenyl-2,3-dihydro-1H-2-phosphoniaphenalene bromide was performed. 1,8-Bis(diphenylphosphino)naphthalene and α,α′-dibromo-o-xylene afforded—despite unfavorable steric strain—the first dialkylation product of 1,8-bis(phosphino)naphthalene, namely corresponding cyclic bisphosphonium salt. The use of acetonitrile as the solvent was the key for this synthesis. The bromide anions were exchanged in metathesis reaction with hexafluorophosphate anions and the new compound was fully characterized including single crystal X-ray diffraction. The large distance between phosphorus atoms of 3.974 Ǻ clearly demonstrate a strong proximity effect in this hindered bisphosphonium salt.

Synthesis and Structure–Activity Analysis of New Phosphonium Salts with Potent Activity against African Trypanosomes

A series of 73 bisphosphonium salts and 10 monophosphonium salt derivatives were synthesized and tested in vitro against several wild type and resistant lines of Trypanosoma brucei (T. b. rhodesiense STIB900, T. b. brucei strain 427, TbAT1-KO, and TbB48). More than half of the compounds tested showed a submicromolar EC(50) against these parasites. The compounds did not display any cross-resistance to existing diamidine therapies, such as pentamidine. In most cases, the compounds displayed a good selectivity index versus human cell lines. None of the known T. b. brucei drug transporters were required for trypanocidal activity, although some of the bisphosphonium compounds inhibited the low affinity pentamidine transporter. It was found that phosphonium drugs act slowly to clear a trypanosome population but that only a short exposure time is needed for irreversible damage to the cells. A comparative molecular field analysis model (CoMFA) was generated to gain insights into the SAR of this class of compounds, identifying key features for trypanocidal activity.

Synthesis of bis-phosphonium salts from 6-bromo-1,2-naphthoquinone and α,ω-bis(diphenylphosphino)alkanes

1,4-Bis(diphenylphosphino)butane and 1,5-bis(diphenylphosphino)pentane add two molecules of 6-bromo-1,2-naphthoquinone to afford bis-ylides which on treatment with protic acids are converted into the corresponding P,P’-bis(7-bromo-3,4-dihydroxy-1-naphthyl)-substituted bis-phosphonium salts.

New Benzophenone-Derived Bisphosphonium Salts as Leishmanicidal Leads Targeting Mitochondria through Inhibition of Respiratory Complex II

A set of benzophenone-derived bisphosphonium salts was synthesized and assayed for lethal activity on the human protozoan parasite Leishmania. A subset of them, mostly characterized by phosphonium substituents with an intermediate hydrophobicity, inhibited parasite proliferation at low micromolar range of concentrations. The best of this subset, 4,4'-bis((tri-n-pentylphosphonium)methyl)benzophenone dibromide, showed a very scarce toxicity on mammalian cells. This compound targets complex II of the respiratory chain of the parasite, based on (i) a dramatically swollen mitochondrion in treated parasites, (ii) fast decrease of cytoplasmic ATP, (iii) a decrease of the electrochemical mitochondrial potential, and (iv) inhibition of the oxygen consumption rate using succinate as substrate. Thus, this type of compounds represents a new lead in the development of leishmanicidal drugs.

Dinuclear Gold Complexes of Two Simple but Underutilized Dicarbanionic Ligand Types

Both mono- and bisylide zwitterionic complexes of gold(I), [(C6F5){PhCH(PPh3)}Au] (4), [(C6F5)2(C6H4-p){CH(PPh3)}2Au5] (5) and [(C6F5)2(C6H4-m){CH(PPh3)}2Au2] (6) were prepared by THT substitution in [C6F5(THT)Au] (THT = tetrahydrothiophene) using deprotonated mono- and bis-phosphonium salts. Lithiation of 4,4'-dibromo-2,3,5,6,2',3',5',6'-octafluoro-1,1_- biphenyl and transmetallation with [Cl(Ph3P)Au] produced a dinuclear gold complex of octafluorosubstituted biphenyl [[(PPh3)2(C6F4-C6F4)2Au2]] (8)

Substituent effect on the optoelectronic properties of poly(p‐phenylenevinylene) based conjugated‐nonconjugated copolymers

AbstractTwo classes of light emitting Poly(p‐phenylenevinylene) (PPV) based conjugated‐nonconjugated copolymers (CNCPs) have been synthesized. The conjugated chromophores containing 2‐methoxy‐5‐(2′‐ethylhexyloxy)‐1,4‐phenylenevinylene (MEHPV) and 2,5‐dimethyl‐1,4‐phenylenevinylene (DMPV) moieties are rigid segments and nonconjugated portion containing hexyl units are flexible in nature. All copolymers were synthesized by well‐known Wittig reaction between the appropriate bisphosphonium salts and the dialdehyde monomers. The resulting polymers were found to be readily soluble in common organic solvents like chloroform, THF and chlorobenzene. The effect of chromophore substituents on the optical and redox properties of the copolymers has been investigated. Color tuning was carried out by varying the molar percentage of the comonomers. The UV‐Vis absorption and PL emission of the copolymers were in the range 314–395 nm and 494–536 nm respectively. All the polymers show good thermal stability. Polymer light‐emitting diodes (PLEDs) were fabricated in ITO/PEDOT:PSS/emitting polymer/cathode configurations of selected polymers using double‐layer, LiF/Al cathode structure. The emission maxima of the polymers were around 499–536 nm, which is a blue‐green part of the color spectrum. The threshold voltages of the EL polymers were in the range of 5.4–6.2 V. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

C−P and C−H Bond Activations and C−C Coupling in Bis-Phosphonium Salts Induced by Platinum(II) Complexes

The reaction of [Ph3PCH2-(E)-C(Me)C(H)PPh3]Cl2 (1b) with PtCl2(NCPh)2 (1:1 molar ratio) in refluxing 2-methoxyethanol gives the ortho-metalated complex [Pt(C6H3-3-Ph-2-PPh2-CC(Me)CH2PPh2-κC,C,P)Cl] (3). The synthesis of complex 3 formally involves three C−H and one C−P bond activation and one C−C bond coupling. Complex 3 reacts with excess KBr or NaI to give, after halide metathesis, the complexes [Pt(C6H3-3-Ph-2-PPh2-CC(Me)CH2PPh2-κC,C,P)X] (X = Br (4), I (5)). Complex 5 has been characterized by X-ray diffraction methods. The influences of several factors, such as the solvent, the platinum starting complex, and the bis-phosphonium salt, in the synthesis of 3 have been examined, and a plausible reaction mechanism for the synthesis of 3 is proposed. This mechanism is supported by the isolation of the Pt(IV) derivative [Pt(C6H4-4-F){C6H3-5-F-2-P(p-FC6H4)2-CC(Me)CH2P(p-FC6H4)2-κC,C,P}Cl2] (6), obtained by reaction of [(p-FC6H4)3PCH2-(E)-C(Me)C(H)P(p-FC6H4)3]Cl2 (1f) with PtCl2(NCPh)2 in refluxing 2-methoxye...

C−H Activation in Phosphonium Salts Promoted by Platinum(II) Complexes

The reaction of PtCl2(NCPh)2 with the bis-phosphonium salts {[R2PhPCH2]2C(O)}Cl2 (R2 = Ph2, PhEt, Et2) (1:1 molar ratio) in refluxing 2-methoxyethanol affords the C,C-orthometalated complexes [PtCl2(C6H4-2-PR2C(H)C(O)CH2PPhR2)] (R2 = Ph2 1a, PhEt 1b, Et2 1c). The reaction of PtCl2 with the bis-phosphonium salt {[Ph3PCH2]2C(O)}Cl2 (1:1 molar ratio) gives {[Ph3PCH2]2C(O)}[PtCl4], 2, while treatment of PtCl2 with the perchlorate salts {[R2PhPCH2]2C(O)}(ClO4)2 (1:1 molar ratio) results in the formation of the cationic dinuclear orthometalated derivatives [Pt(μ-Cl)(C6H4-2-PR2C(H)C(O)CH2PPhR2)]2(ClO4)2 (R2 = Ph2 3a, PhEt 3b, Et2 3c). The cycloplatination of the bis-phosphonium salts to give the C,C-orthometalated derivatives implies two C−H bond activation processes at two types of carbon atoms, one arylic and one alkylic. The reaction of PtCl2(NCPh)2 or PtCl2 with the allyl-phosphonium salts [PhR2PCH2CHCH2]Cl (R2 = Ph2, Me2) or [Ph3PCH2CHCHMe]Cl (1:1 molar ratio) in refluxing 2-methoxyethanol gives the orthometalated vinyl-phosphonium derivatives [PtCl2(C6H4-2-PR2-η2-E-C(H)C(H)CH3)] (R2 = Ph2 4a, Me2 4b) or [PtCl2(C6H4-2-PPh2-η2-E-C(H)C(H)CH2CH3)], 7, respectively, while the reaction of PtCl2 with [Ph3PCH2CHCH2]ClO4 (1:1 molar ratio) gives the η2-olefin-bonded derivative [Cl3Pt(η2-CH2CH−CH2PPh3)], 5. The reaction of [Ph3PCH2CHCHPh]Cl with PtCl2 (1:1 molar ratio, 2-methoxyethanol, reflux) gives an easily separable mixture of products: the η2-olefin-bonded [Cl3Pt(η2-CHPhCH−CH2PPh3)], 8, and the orthometalated [PtCl2(C6H4-2-PPh2-η2-E-C(H)C(H)CH2Ph)], 9, while the reaction of [Ph3PCH2CMeCH2]Cl with PtCl2 (1:1 molar ratio) gives a mixture of the cycloplatinated [PtCl2(C6H4-2-PPh2-η2-C(H)CMe2)], 10, and the isomerized vinyl-phosphonium salt [Ph3P−C(H)CMe2]Cl, 11. The synthesis of complexes 4, 7, 9, and 10 implies the activation of one C(aryl)−H bond (instead of the more active methylene group adjacent to the phosphonium unit P−CH2) and the rearrangement of the allyl group into a vinyl group by 1,3-prototropic shift, this shift being produced in the absence of external base. The complexes 4a·CH2Cl2 and 8 have been characterized by X-ray diffraction methods.

New Synthetic Approach to Phosphonium Salts Derived from 4,5-Bis(diphenylphosphino)-1-phenylpyridazin-6-one and Quantum-Chemical Calculations of Their Formation

4,5-Bis(diphenylphosphino)-1-phenylpyridazin-6-one reacts with ethyl iodide, 1,2-dichloroethane, 1,2-dibromomehtane, and o-dibromobenzene to give the corresponding bis-phosphonium salts which, depend- ing on the halogen derivative, can undergo further transformations involving cleavage of the PAC bond in the β-position with respect to the carbonyl group.

The syntheses and structures of salts of the octachlorodirhenate(III) and octachlorodiosmate(III) anions with the 1,2-bis(triphenylphosphonium) ethane cation

The reactions of cis-Re 2(O 2CCH 3) 2Cl 4(py) 2 or ( n-Bu 4N) 2Re 2Cl 8, with PR, (R = Cy or Ph) in refluxing 1,2-dichloroethane afford the bis-phosphonium salts (R 3PCH 2CH 2PR 3)Re 2Cl 8; the crystal structure of the derivative where R = Ph shows that this is only the second example of a salt of the [Re 2Cl 8] 2 anion in which a 3-fold orientational disorder of the ReRe units is encountered. Å cation exchange reaction between (Ph 3PCH 2CH 2PPh 3)CI 2 and ( n-Bu 4N) 2Os 4Cl 8 affords (Ph 3PCH 2CH 2PPh 3)Os 2Cl 8,, which possesses an OsOs bond distance of 2.1896(3) Å and is the second example of a crystal structure of a [Os 2Cl 8] 2− salt in which a fully staggered rotational geometry is present.

STUDIES ON THE WITTIG REACTION (XXV): THE STEREOCHEMISTRY OF BIS-WITTIG REACTION BETWEEN AROMATIC ALDEHYDES AND 1,2 AND 1,3 BIS-YLIDES

Abstract 1,2 and 1,3 bis-ylides derived from corresponding bis-phosphonium salts reacted with substituted benzaldehydes to give 19 dienes with E,E-selectivity.

Synthesis and Optical Characterization of Polydiacetylenes Containing Carboxylic Acid, Carbamate, Phosphonium, and Quaternary Ammonium Functionalities

Symmetrically substituted 1,3-diynes, X(CH2)nC⋮CC⋮C(CH2)nX (X = Et2N; n = 4, 9; 1d,e) have been prepared from the appropriate bis-tosylates (X = OSO2C6H4Me-p; 1b,c) and diethylamine, and one such derivative has been converted into a bis-quaternary ammonium salt (X = N+Et2MeI-; n = 4; 1f) and an ammonium sulfonate inner salt (X = N+Et2(CH2)3SO3-; n = 4; 1g), respectively. Three bis-phosphonium salts, X(CH2)nC⋮CC⋮C(CH2)nX (X = P+Ph3Br-; n = 4, 9, 3; 1h−j), were synthesized from 1,4-bis(bromoalkyl)-1,3-diynes and the appropriate phosphine derivative. The new diyne derivatives did not polymerize on exposure to γ-irradiation or electron beam irradiation in a Van der Graff linear accelerator. The tosylated polydiacetylene (PDA) derivative (2a, “PTS-12”) derived from 1b was treated with diethylamine to yield a tertiary amine-functionalized PDA derivative (2b), and the latter was allowed to react (separately) with methyl iodide and 1,3-propanesultone to give ionomeric PDAs 2c and 2d, respectively. The phosphinate...