Phosphine Derivatives Research Articles

Copper(I) complexes with phosphine derived from sparfloxacin. Part II: a first insight into the cytotoxic action mode.

In this paper we present a first insight into the cytotoxic action mode of copper(I) iodide or copper(I) thiocyanate complexes with a phosphine derivative of sparfloxacin (a 3rd generation fluoroquinolone antibiotic agent) and 2,9-dimethyl-1,10-phenanthroline or 2,2'-biquinoline as auxiliary ligands. The in vitro cytotoxic activity of the new complexes was tested against two cancer cell lines (CT26--mouse colon carcinoma and A549--human lung adenocarcinoma). An ICP-MS study revealed a marked time-dependent intracellular copper accumulation of the tested compounds. In addition, confocal microscopy imaging showed accumulation of the complexes inside whole cells and their emission of blue light. The complexes generate reactive oxygen species in the cancer cells, which was examined by using two different fluorescent probes. Moreover, (I) DNA intercalation studied by luminescence spectroscopy, circular dichroism and molecular docking, and (II) plasmid DNA damage also demonstrate their significant cytotoxicity. All these observed biological effects contribute to the induction of apoptosis, observed at a great predominance.

Synergistic effects in ambiphilic phosphino-borane catalysts for the hydroboration of CO2.

The benefit of combining both a Lewis acid and a Lewis base in a catalytic system has been established for the hydroboration of CO2, using ferrocene-based phosphine, borane and phosphino-borane derivatives.

ChemInform Abstract: Synthetic Applications of Hypophosphite Derivatives in Reduction

AbstractReview: [197 refs.

A computational study on [(PH2X)2]·+ homodimers involving intermolecular two-center three-electron bonds

A computational study at CCSD(T) theoretical level has been carried out on radical cation [(PH2X)2]·+ homodimers. Four stable minima configurations have been found for seven substituted phosphine derivatives, X = H, CH3, CCH, NC, OH, F and Cl. The most stable minimum presents an intermolecular two-center three-electron P···P bond except for X = CCH. The other three minima correspond to an alternative P···P pnicogen bonded complex, to a P···X contact and the last one to the complex resulting from a proton transfer, PH3X+:PHX·. The complexes obtained have been compared with those of the corresponding neutral ones, (PH2X)2, and the analogous protonated ones, PH3X+:PH2X, recently described in the literature. The spin and charge densities of the complexes have been examined. The electronic characteristics of the complexes have been analyzed with the NBO and AIM methods. The results obtained for the spin density, charge and NBO are coherent for all the complexes.

Synthesis of a Phosphinate Analogue of the Antitumour Phospholipid Edelfosine

AbstractThe first concise synthesis of a phosphinate analogue of the antitumour ether phospholipid edelfosine is described. The key synthetic step comprised the free‐radical addition reaction of phosphinic acid to a functionalised allyl ether, to incorporate the hydrophobic tail into a monosubstituted H‐phosphinic acid. The hydrophilic head group was then added by using a silyl phosphonite based Michael addition. The reported synthetic study lays the groundwork for the synthesis of modified phosphinate phospholipid derivatives to facilitate investigations on their biological activity as membrane‐targeting antitumour agents.

The Synthesis and Potential Use of Cyclic Phosphinic Acid Derivatives

GRAPHICAL ABSTRACT

Phosphine derivatives of sparfloxacin – Synthesis, structures and in vitro activity

We synthesized two derivatives of sparfloxacin (HSf): aminomethyl(diphenyl)phosphine (PSf) and its oxide (OPSf). The compounds were characterized by NMR spectroscopy, MS and elemental analysis. In addition, the molecular structures of the compounds were determined using DFT and X-ray (OPSf) analysis. The antibacterial activity of HSf and both derivatives was tested against four reference and fifteen clinical Gram-positive and Gram-negative strains of bacteria (sensitive or resistant to fluoroquinolones). The results showed that the activity of PSf was similar to or higher than the activity of HSf, while OPSf was found significantly less active. The compounds were also tested in vitro toward the following cancer cell lines: mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). Regardless of the cancer cell line, derivatization of HSf resulted in the gradual increase of cytotoxicity. OPSf exhibited the highest one (4h – incubation time: IC50(CT26)=51.0±1.2; IC50(A549)=74.9±1.4 and 24h: IC50(CT26)=109.2±8.8; IC50(A549)=52.7±9.2).

ChemInform Abstract: PCN Pincer Palladium(II) Complex Catalyzed Enantioselective Hydrophosphination of Enones: Synthesis of Pyridine‐Functionalized Chiral Phosphine Oxides as NCsp3O Pincer Preligands.

A series of chiral PCN pincer Pd(II) complexes VI–XIII with aryl-based aminophosphine–imidazoline or phosphinite–imidazoline ligands were synthesized and characterized. They were examined as enantioselective catalysts for the hydrophosphination of enones. Among them, complex IX, which features a Ph2PO donor as well as an imidazoline donor with (4S)-phenyl and N-Tol-p groups, was found to be the optimal catalyst. Thus, in the presence of 2–5 mol % of complex IX a wide variety of enones reacted smoothly with diarylphosphines to give the corresponding chiral phosphine derivatives in high yields with enantioselectivities of up to 98% ee. In particular, heteroaryl species such as 2-thienyl-, 2-furyl-, and 2-pyridinyl-containing enones that have a strong coordination ability to the Pd center were also appropriate substrates for the current catalytic system. For example, hydrophosphination of 2-alkenoylpyridines with diphenylphosphine followed by oxidation with H2O2 afforded the corresponding pyridine-functional...

Fosinopril sodium–hydroxypropyl-β-cyclodextrin inclusion complex

Fosinopril, the unique phosphinic acid derivative among the angiotensin-converting enzyme inhibitors, is a poorly water-soluble and highly lipophilic substance, exhibiting poor bioavailability following oral administration. The inclusion complex between the drug substance and hydroxypropyl-β-cyclodextrin (HPBCD) was obtained in order to improve its solubility and, consequently, its bioavailability. The aim of this study was to investigate the thermoanalytical behavior of fosinopril sodium (FOS), of the inclusion complex between FOS and HPBCD (FOS/HPBCD) and its physical mixture with some pharmaceutical excipients commonly used in solid dosage forms. The analytical techniques used for this purpose have been thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FT-IR). Non-isothermal methods have been employed to determine the kinetic parameters using DTG data. The DTA curves of inclusion complex FOS/HPBCD and its 1:1 (m/m) physical mixtures with excipients (magnesium stearate, talc and starch) indicated a possible interaction of the inclusion complex (IC) with magnesium stearate and talc. FT-IR data and the values of the activation energy (E a) for physical mixture did not evidence any incompatibility between the IC and excipients. Concerning FOS, the thermoanalytical results and the value of E a for the binary mixture of drug with magnesium stearate confirmed the incompatibility between the two substances reported in the literature. Therefore, as a result of the encapsulation of FOS in the HPBCD cavity, the stabilization of drug substance in the presence of magnesium stearate has been realized.

Reduction of phosphine oxides to the corresponding phosphine derivatives in Mg/Me3SiCl/DMI system

Direct reductions of phosphine oxides to the corresponding phosphines were performed successfully by using Mg/Me3SiCl/DMI system. The reduction proceeded under mild conditions and was applicable to a wide range of phosphine oxides; triarylphosphine oxides, alkyldiarylphosphine oxides, and dialkylarylphosphine oxides gave the corresponding phosphines in good to excellent yields.

Copper(i) complexes with phosphine derived from sparfloxacin. Part I - structures, spectroscopic properties and cytotoxicity.

In this paper we present new copper(i) iodide or copper(i) thiocyanate complexes with hydroxymethyldiphenylphosphine (PPh2(CH2OH)) or phosphine derivatives of sparfloxacin, a 3(rd) generation fluoroquinolone antibiotic agent (PPh2(CH2-Sf)) and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) auxiliary ligands. The synthesised complexes were fully characterised by NMR and UV-Vis spectroscopy as well as by mass spectrometry. Selected structures were additionally analysed using X-ray and DFT methods. All complexes proved to be stable in solution in the presence of water and atmospheric oxygen for several days. The cytotoxic activity of the complexes was tested against two cancer cell lines (CT26 - mouse colon carcinoma and A549 - human lung adenocarcinoma). Applying two different incubation times, the studies enabled a preliminary estimation of the dependence of the selectivity and the mechanism of action on the type of diimine and phosphine ligands. The results obtained showed that complexes with PPh2(CH2-Sf) are significantly more active than those with PPh2(CH2OH). On the other hand, the relative impact of diimine on cytotoxicity is less pronounced. However, the dmp complexes are characterised by strong inhibitory properties, while the bq ones are rather not. This confirms the interesting and promising biological properties of the investigated group of copper(i) complexes, which undoubtedly are worthy of further biological studies.

Coordination versatility of phosphine derivatives of fluoroquinolones. New CuIand CuIIcomplexes and their interactions with DNA

This paper describes syntheses and interactions with DNA of copper(i) and copper(ii) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin and norfloxacin).

PCN pincer palladium(II) complex catalyzed enantioselective hydrophosphination of enones: synthesis of pyridine-functionalized chiral phosphine oxides as NC(sp(3))O pincer preligands.

A series of chiral PCN pincer Pd(II) complexes VI-XIII with aryl-based aminophosphine-imidazoline or phosphinite-imidazoline ligands were synthesized and characterized. They were examined as enantioselective catalysts for the hydrophosphination of enones. Among them, complex IX, which features a Ph2PO donor as well as an imidazoline donor with (4S)-phenyl and N-Tol-p groups, was found to be the optimal catalyst. Thus, in the presence of 2-5 mol % of complex IX a wide variety of enones reacted smoothly with diarylphosphines to give the corresponding chiral phosphine derivatives in high yields with enantioselectivities of up to 98% ee. In particular, heteroaryl species such as 2-thienyl-, 2-furyl-, and 2-pyridinyl-containing enones that have a strong coordination ability to the Pd center were also appropriate substrates for the current catalytic system. For example, hydrophosphination of 2-alkenoylpyridines with diphenylphosphine followed by oxidation with H2O2 afforded the corresponding pyridine-functionalized chiral phosphine oxides in good yields with good to excellent enantioselectivities (10 examples, up to 95% ee). Furthermore, it had been demonstrated that the obtained pyridine-containing phosphine oxide acted as a tridentate ligand in the reaction with PdCl2 to form an intriguing NCsp(3)O pincer Pd(II) complex via Csp(3)-H bond activation, which to our knowledge is the first example of a chiral DCsp(3)D' Pd pincer (D ≠ D'; D and D' denote donor atoms such as P, N, etc.).

Stereocontrolled synthesis of phosphinyl dipeptide isosteres using an asymmetric center at the phosphorus atom

Phosphinyl dipeptide isosteres (PDIs) are important compounds for the development of potent and selective inhibitors of various aspartic proteases and Zn metalloproteases. The stereochemistry of PDIs affects their biological activity. PDIs were prepared successfully using the concept of asymmetric induction from the chiral phosphorus atom of the phosphinate moiety to the neighboring carbon atom. This methodology involves diastereoselective α-alkylation and β'-alkylation of P-chiral phosphinate derivatives, prepared through lipase-catalyzed kinetic resolution, which produces Phe-Ala type and Pro-Phe type PDIs. The synthesis of Leu-Pro type PDIs in a protected form was achieved through a cross-coupling reaction of stereodefined α-amino-H-phosphinate with alkenyl triflate, followed by diastereoselective hydrogenation of the alkene moiety.

Characterizing traditional and chlorine-shared halogen bonds in complexes of phosphine derivatives with ClF and Cl2.

Ab initio MP2/aug'-cc-pVTZ calculations have been carried out on the halogen-bonded complexes H2XP:ClF and H2XP:Cl2, with X = F, Cl, OH, NC, CN, CCH, CH3, and H. H2XP:ClF complexes are stabilized by chlorine-shared halogen bonds with short P-Cl and significantly elongated Cl-F distances. H2XP:Cl2 complexes with X = OH and CH3 form only chlorine-shared halogen bonds, while those with X = H, NC, and CN form only traditional halogen bonds. On the H2FP:Cl2, H2(CCH)P:Cl2, and H2ClP:Cl2 potential surfaces small barriers separate two equilibrium structures, one with a traditional halogen bond and the other with a chlorine-shared bond. The binding energies of H2XP:ClF and H2XP:Cl2 complexes are influenced by the electron-donating ability of H2XP and the electron accepting ability of ClF and ClCl, the nature of the halogen bond, other secondary interactions, and charge-transfer interactions. Changes in electron populations on P, F, and Cl upon complex formation do not correlate with changes in the chemical shieldings of these atoms. EOM-CCSD spin-spin coupling constants for complexes with chlorine-shared halogen bonds do not exhibit the usual dependencies on distance. (2X)J(P-F) and (2X)J(P-Cl) for complexes with chlorine-shared halogen bonds do not correlate with P-F and P-Cl distances, respectively. (1X)J(P-Cl) values for H2XP:ClF correlate best with the Cl-F distance, and approach the values of (1)J(P-Cl) for the corresponding cations H2XPCl(+). Values of (1X)J(P-Cl) for complexes H2XP:ClCl with chlorine-shared halogen bonds correlate with the binding energies of these complexes. (1)J(F-Cl) and (1)J(Cl-Cl) for complexes with chlorine-shared halogen bonds correlate linearly with the distance between P and the proximal Cl atom. In contrast, (2X)J(P-Cl) and (1X)J(P-Cl) for complexes with traditional halogen bonds exhibit more normal distance dependencies.

Complexes between hypohalous acids and phosphine derivatives. Pnicogen bond versus halogen bond versus hydrogen bond

The complexes of HOBr:PH2Y (Y=H, F, Cl, Br, CH3, NH2, OH, and NO2), HOCl:PH2F, and HOI:PH2F have been investigated with ab initio calculations at the MP2/aug-cc-pVTZ level. Four types of structures (1, 2, 3a, and 3b) were observed for these complexes. 1 is stabilized by an O⋯P pnicogen bond, 2 by a P⋯X halogen bond, 3a by a H⋯P hydrogen bond and a P⋯X pnicogen bond, and 3b by H⋯P and H⋯Br hydrogen bonds. Their relative stability is related to the halogen X of HOX and the substituent Y of PH2Y. These structures can compete with interaction energy of −10.22∼−29.40kJ/mol. The HO stretch vibration shows a small red shift in 1, a small irregular shift in 2, but a prominent red shift in 3a and 3b. The XO stretch vibration exhibits a smaller red shift in 1, a larger red shift in 2, but an insignificant blue shift in 3a and 3b. The PY stretch vibration displays a red shift in 1 but a blue shift in 2, 3a, and 3b. The formation mechanism, stability, and properties of these structures have been analyzed with molecular electrostatic potentials, orbital interactions, and non-covalent interaction index.

Enantioselective Hydrophosphination of Enones with Diphenylphosphine Catalyzed by Bis(imidazoline) NCN Pincer Palladium(II) Complexes

A series of chiral NCN pincer Pd(II) complexes with 1,3-bis(2′-imidazolinyl)phenyl (Phebim) ligands were synthesized via the C–H activation or oxidative addition method. A dinuclear macrocyclic Pd(II) complex was also prepared by reaction of the Phebim-H ligand with PdCl2. All of the new compounds were fully characterized, and X-ray single-crystal structures were obtained for two of the complexes. The Pd(II) complexes were successfully applied to enantioselective hydrophosphination of various enones with diphenylphosphine, providing optically active phosphine derivatives in good yields with enantioselectivities of up to 94% ee.

Crystal Structure Characterization and Catalytic Application of Novel Route Prepared Ru3(CO)9 DPAM (Diphenyl Arsino Methane)-tri Phenyl Phosphine Derivatives

Triruthenium dodecacarbonyl-Ru3(CO)12 based diphenylarsino methane-triphenyl phosphine derivatives, such as Ru3(CO)9-dpam-tris (methyl phenyl) phosphine (1), Ru3(CO)9-dpam-tris (methoxy phenyl) phosphine (2), and Ru3(CO)9-dpam-tris (fluro phenyl) phosphine (3) are synthesized by two step modified method. The catalytic hydrogenation of cyclohexene, styrene, and phenyl acetylene, on above mentioned Ru-based organometallic catalysts, has been studied under high pressure hydrogen atmosphere. The high pressure hydrogenation of cyclohexene and phenyl acetylene on Complex (1–3), showed good catalytic activity under pressurized condition. Hydrogenation of cyclohexene on Complex (3) showed better (50–65%) conversion in the presence of toluene than hexane solvent. The effect of temperature, role of solvent, and pressure conditions have also been studied.

Synthesis of Phosphinic Acid Derivatives; Traditional Versus up-to-Date Synthetic Procedures

Synthetic methods for the preparation of phosphinic derivatives (esters and amides) are summarized. The basic method is, when phosphinic chlorides are reacted with alcohols or amines. These reactions take place under mild conditions, but utilize expensive chlorides, need a solvent, and a base has to be added to remove the HCl formed. On conventional heating, the phosphinic acids resist undergoing derivatizations by nucleophiles. However, on microwave (MW) irradiation, the phosphinic acids could be esterified by alcohols. The direct esterification does not require an extra solvent, it is atomic efficient, but needs a relatively higher temperature. The similar amidations were reluctant. Phosphinic acids may also be esterified by alkylation that may be promoted by combined phase transfer catalysis and MW irradiation. It is also possible to convert the phosphinic acids by different reagents (e.g. by the T3Pi›š reactant) to a more reactive intermediate that is ready to react with alcohols or amines. Other methods, such as preparation by the Arbuzov reaction or by fragmentation-related phosphorylation are also discussed.

First Example of Alkyl–Aryl Negishi Cross-Coupling in Flow: Mild, Efficient and Clean Introduction of Functionalized Alkyl Groups

Abstract The first example of an alkyl-aryl Negishi coupling in a practical, sustainable, and high-yielding process using a silica-supported catalyst in flow is described. Excellent conversions and good functional group compatibility were obtained under very mild conditions. Functionalized alkyl groups were also introduced to provide access to synthetically useful molecules and to demonstrate the versatility of the method. The scalability was assessed, and a throughput of 7.5 mmol/h of processed substrate was achieved. All crude products were free from phosphine derivatives and ready for use in subsequent reaction steps.