TPPTS Research Articles

Synthesis of Water-Soluble Phosphinophenol for Traceless Staudinger Ligation

The traceless Staudinger ligation can be mediated in water without organic co-solvents if charged groups render the phenylphosphine reagent water soluble. Here the synthesis of a new water-soluble phosphine is presented based on a diphenylphosphinophenol reagent. Staudinger ligation with this reagent and azido glycine amide showed conversion of 77%.

Anticancer Therapeutics That Target Selenoenzymes: Synthesis, Characterization, in vitro Cytotoxicity, and Thioredoxin Reductase Inhibition of a Series of Gold(I) Complexes Containing Hydrophilic Phosphine Ligands

Gold(I) complexes bearing water-soluble phosphine ligands, including 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA), and sodium triphenylphosphine trisulfonate (TPPTS), in combination with thionate ligands, were screened for their antiproliferative activities against human ovarian cancer cell lines A2780 either sensitive or resistant to cisplatin. In addition, the compounds were screened for their inhibition of mammalian thioredoxin reductases (TrxR), enzymes that are overexpressed in many tumor cells and contribute to drug resistance. The gold(I)-phosphine complexes efficiently inhibited cytosolic and mitochondrial TrxRs at concentrations that did not affect the related oxidoreductase glutathione reductase (GR). Additional complementary information on the enzyme metallation process and potential gold binding sites was obtained through the application of a specific biochemical assay using a thiol-tagging reagent, BIAM (biotin-conjugated iodoacetamide).

Water soluble phosphine rhenium complexes

Reduction of [NMe4]2[ReBr5(NO)] (1) with zinc in acetonitrile leads to the known trisacetonitrile compound [ReBr2(CH3CN)3(NO)] (2). Attempts to turn 2 into a dihydrogen or a hydride complex applying direct reaction with H2 or with H2 and a base were unsuccessful. Complex 2 could be transformed into [ReBr(BF4)mer(CH3CN)3(NO)] (2a) with AgBF4 in acetonitrile and was used as a starting material in a ligand exchange reaction with the water soluble phosphine 1,3,5-triaza-7-phosphadamantane (PTA) to obtain the complex [ReBr2(NO)(PTA)3 ]( 3). When the reduction of 1 with zinc was carried out in the presence of PTA in acetonitrile, the disubstituted complex [ReBr2(CH3CN)(NO)(PTA)2 ]( 4) was formed. The olefin-coordinated rhenium complexes [ReBr2(NO)(CH2@CH2)(PTA)2 ]( 5a) and [ReBr2(NO)(PhCH@CH2)(PTA)2 ]( 5b) were obtained from the reaction of 4 with the corresponding olefins. Complex 4 reacts further with NaHBEt3 in THF to give the dihydride [ReH2(THF)(NO)(PTA)2 ]( 6). In the presence of ethylene 6 is transformed into the ethyl hydride complex [ReH(CH2CH3)(g

Aqueous Wittig reactions of semi-stabilized ylides. A straightforward synthesis of 1,3-dienes and 1,3,5-trienes

A direct synthesis of 1,3-dienes and 1,3,5-trienes from the reaction of semi-stabilized ylides and a range of saturated and unsaturated aldehydes is reported in water as solvent, employing sodium hydroxide as base. The water-soluble phosphine oxide side product is removed simply by aqueous partitioning of the organic products.

Oxidation of a Water-Soluble Phosphine and Some Spectroscopic Probes with Nitric Oxide and Nitrous Acid in Aqueous Solutions

In acidic aqueous solutions, nitrogen monoxide oxidizes monosulfonated triphenylphosphine, TPPMS(-), to the corresponding phosphine oxide. The NO-derived product is N(2)O. This chemistry parallels that reported for the reaction of NO with the unsubstituted triphenylphosphine in nonpolar organic solvents, but the rate constant measured in this work, 5.14 x 10(6) M(-2) s(-1), is greater by several orders of magnitude. This makes TPPMS(-) a useful analytical reagent for NO in aqueous solution. The increased rate constant in the present work appears to be a medium effect, and unrelated to the introduction of a single sulfonate group in the phosphine. The reaction between nitrous acid and TPPMS(-) has a 2:1 [TPPMS(-)]/[HNO(2)] stoichiometry and generates NH(2)OH quantitatively. The rate law, rate = 4k(d)[HNO(2)](2)[TPPMS(-)], identifies the second-order self-reaction of HNO(2) as the rate-limiting step that generates the active oxidant(s) for the fast subsequent reaction with TPPMS(-). It appears that the active oxidant is N(2)O(3), although the oxides NO and NO(2) derived from it may be also involved. Bimolecular self-reaction of HNO(2) also precedes the oxidations of ABTS(2-) and TMPD. Competing with this path are the acid-catalyzed oxidations of both reagents via NO(+).

Synthesis of Water-Soluble Dendritic Phosphine Ligands and Their Application to Hydration of Alkynes in Aqueous Media

Abstract A series of water-soluble dendritic ligands with a phosphine core was synthesized through the coupling of tris(4-hydroxyphenyl)phosphine oxide with poly(benzyl ether) dendron having tri(ethylene glycol) units, followed by reduction. By employing the corresponding water-soluble phosphine–gold(I) dendrimers as a catalyst, the hydration of alkynes proceeded smoothly. Furthermore, by membrane separation based on the nano-order size of the dendritic catalyst, the gold(I) catalyst was recycled without deactivation.

Synthesis and characterization of water-soluble palladium(II)-functionalized diphosphine complexes

Water-soluble functionalized bis(phosphine) ligands L ( a– h) of the general formula CH 2(CH 2PR 2) 2, where for a: R = (CH 2) 6OH; b– g: R = (CH 2) n P(O)(OEt) 2, n = 2–6 and n = 8; h: R = (CH 2) 3NH 2 ( Scheme 1), have been prepared photochemically by hydrophosphination of the corresponding 1-alkenes with H 2P(CH 2) 3PH 2. Water-soluble palladium complexes cis-[Pd( L)(OAc) 2] ( 1– 8) were obtained by the reaction of Pd(OAc) 2 with the ligands a– h in a 1:1 mixture of dichloromethane:acetonitrile. The water-soluble phosphine ligands and their palladium complexes were characterized by IR, 1H and 31P NMR. A crystallographic study of complex 1 shows that the Pd(II) ion has a square planar coordination sphere in which the acetate ligands and the diphosphine ligand deviate by less than 0.12 Å from ideal planar.

Efficient Synthesis of Water-Soluble Alkyl-bis(m-sulfonated-phenyl)- and Dialkyl-(m-sulfonated-phenyl)-phosphines and Their Evaluation in Rhodium-Catalyzed Hydrogenation of Maleic Acid in Water

The combined application of 31P NMR and pH measurements during the tri-isooctylamine-assisted aqueous/organic separation and purification steps after the sulfonation of diphenyl-alkyl-phosphines (Ph2PR; R = Me, n-Bu) and phenyl-dialkyl-phosphines (PhPR2; R = Me, n-Bu) resulted in the preparation of water-soluble alkyl-bis(m-sulfonated-phenyl)- (C6H4-m-SO3Na)2PR; R = Me, n-Bu) and dialkyl-(m-sulfonated-phenyl)- (C6H4-m-SO3Na)PR2; R = Me, n-Bu) phosphines in the presence of less than 0.5% phosphine oxides. When 2 equiv of the water-soluble phosphines were used per rhodium atom, no significant effect on the turnover frequency of the hydrogenation of maleic acid can be observed by using these phosphines.

Exploring the Water-Soluble Phosphine Ligand as the Environmentally Friendly Stabilizer for Electroless Nickel Plating

Phosphine (R3P) compounds being a typical type of coordination ligand used in homogeneous catalysis are known to possess a tunable affinity with the nickel atom. As such, it deserves to be studied ...

Grafting of water-soluble phosphines to dendrimers and their use in catalysis: positive dendritic effects in aqueous media

Generations 1 to 3 of dendrimers ended by water-soluble phosphines are synthesized and their ruthenium complexes are used as catalysts in aqueous media; a slightly positive dendritic effect on the regioselectivity is observed for hydration of alkynes and a large positive dendritic effect is observed in the biphasic (water/heptane) catalysed isomerisation of allylic alcohols to ketones where the products are easily isolated and the catalyst can be reused several times, even the first generation.

Heterolytic Splitting of Allylic Alcohols with Palladium(0)−TPPTS in Water. Stabilities of the Allylphosphonium Salt of TPPTS and of the Ionic Complex [Pd(η3-allyl)(TPPTS)2]+

The Pd(TPPTS)3 complex (TPPTS is the sodium salt of tris(m-sulfophenyl)phosphine) easily ionizes allyl alcohol in water over a wide range of pH: OH− and TPPTS are released, and [Pd(η3-allyl)(TPPTS)2]+ is formed. The released TPPTS further reacts with the palladium cationic complex to reversibly produce both the allylphosphonium salt of TPPTS [(allyl)Ar3P]+ and Pd(TPPTS)3, the latter acting as the catalyst of the allylation of TPPTS by allyl alcohol. Primary allylic alcohols, such as butenol (trans-2-buten-1-ol), prenol (3-methyl-2-buten-1-ol), geraniol, and cinnamyl alcohol, react with Pd(TPPTS)3 to produce hydroxide ion, the corresponding hydrosoluble cationic palladium complex, and allylic phosphonium salts. At room temperature, [Pd(η3-allyl)(TPPTS)2]+ is stable up to pH 12, but beyond this value, palladium precipitates. The temperature has an adverse effect on the complex stability: palladium precipitates at 80 °C, even at pH 7, with the formation of a small amount of propylene. The addition of [(allyl)Ar3P]+ increases the stability of [Pd(η3-allyl)(TPPTS)2]+. Above pH 10, [(allyl)Ar3P]+ decomposes into OTPPTS and propylene by reaction with OH−. At lower pH, [(allyl)Ar3P]+ is slowly isomerized into [(propenyl)Ar3P]+, which further reduces its stability toward pH and temperature. These consecutive reactions of the TPPTS ligand could explain most of the catalyst instability. This study outlines the basis for a better understanding of the instability phenomenon of the catalytic system Pd(0)−TPPTS in reactions with allylic intermediates, e.g. the Tsuji−Trost reaction, and in the reaction of dienes in aqueous media in which palladium often precipitates.

HER2 guided neoadjuvant treatment of advanced breast cancer: Clinico-biological correlations

11559 Background: Tailoring neoadjuvant chemotherapy (NACT) ± trastuzumab (T) according to tumor/host features remains an open issue, with special reference to anthracycline omission in HER2+ cases. Methods: Patients (pts) with breast cancer (BC), NACT candidate, were eligible. HER2+ pts (n=12) received 24 wks of weekly T 4mg/kg loading dose d1 then 2mg/kg and Paclitaxel (P) 80 mg/m2 before surgery, followed by additional 12 wks of TP and T for 1 year. HER2- pts (n=21) received 8 cycles of epirubicin (E) and docetaxel (D) (90 and 75mg/m2 respectively, q3 wks) before surgery, followed by 3 CMF cycles. Hormone therapy was suggested in all hormone sensitive cases. The primary endpoint was pCR and its correlation with Topo2α expression and the extent of spontaneous T cell responses to HER2 and other BC-associated antigens. Results: The TP regimen gave a clinical response in all 8 evaluable pts (clinical complete remission (CR) in 3 pts, partial remission (PR) in 5). Radical mastectomy (RM and quadrantectomy (Q) were performed in 6 and 2 pts, respectively. Pathologic (p) response rate was 87% with 3 pCR. Nodal pCR occurred in 5/7 pts. The ED regimen gave a 79% clinical response rate in the 14 evaluable pts (CR in 7, PR in 4). RM and Q were performed in 8 and 6 pts, respectively. P response rate was 78.6% with 2 pCR. Nodal pCR occurred in 3/12 pts. Toxicity: onychopathy G3, alopecia G2, paresthesia G2 and mucositis G3 more frequent in the TP pts, neutropenia G3–4, febrile neutropenia, anemia G3 and alopecia G2 more frequent in ED. No cardiotoxicity was observed. Conclusions: This interim analysis suggests that the TP as NACT in HER2+ BC has a good efficacy and tolerability. Clinico-biological correlations are underway. No significant financial relationships to disclose.

Aqueous biphasic catalytic hydroformylation of higher olefins: Promotion effect of cationic gemini and trimeric surfactants

Abstract Six cationic gemini and trimeric surfactants: N,N′-didodecyl-N,N′-dimethyl piperazinium iodide (2), the monooxlate of N,N′-didodecylpiperazine (3), the hydrochloride of N,N′-didodecylpiperazine (4), the 1,3,5-trimethyl-1,3,5-tridodecylhexahydro-1,3,5-trazinium iodide (5), the monooxlate of 1,3,5-tridodecylhexahydro-1,3,5-triazine (6) and the hydrochloride of 1,3,5-tridodecylhexahydro-1,3,5-triazine (7) were prepared using the regular methods. These cationic surfactants and a double-chained surfactant, didodecyldimethylammonium bromide (1), were successfully applied as catalysis promotion agents in aqueous biphasic hydroformylation of higher olefins. The aqueous catalysts used in present study were RhCl(CO)(TPPTS)2–TPPTS [TPPTS: P(m-C6H4SO3Na)3]. The experimental results showed that while all these cationic surfactants could accelerate the hydroformylation reaction, surfactants 1, 2, 6, 7 exhibited more significant promotion effects. The influences of the surfactant anions on the reaction were also discussed. Of the three gemini surfactants 2, 3, and 4, which were derived from N,N′-didodecylpiperazine, surfactant 2 with iodide as anion exhibited substantially higher promotion effect than surfactants 3 with monooxalate and 4 with chloride as anion, respectively. On the other hand, among the three trimeric surfactants 5, 6, 7, which were derived from 1,3,5-tridodecylhexahydro-1,3,5-triazine, surfactants 6 with monooxalate and 7 with hydrochloride as anion displayed better acceleration effect than surfactant 5 with iodide as anion. Compared with the double-chained and single headed surfactant 1, surfactant 2 containing two alkyl chains and cationic heads and surfactant 6 with three alkyl chains and cationic heads were superior additives to accelerate the hydroformylation reactions. When they were used as catalysis promotion additives, less water-soluble phosphine (TPPTS) was required to immobilize the rhodium catalyst in aqueous phase, and the hydroformylation reaction proceeded more regioselectively toward the valuable linear aldehyde under lower syngas pressure.

Insertion of CO2, Ketones, and Aldehydes into the C−Li Bond of 1,3,5-Triaza-7-phosphaadamantan-6-yllithium

The synthesis and structures of a series of new water-soluble phosphine ligands based on 1,3,5-triaza-7-phosphaadamantane (PTA) are described. Insertion of aldehydes or ketones into the C-Li bond of 1,3,5-triaza-7-phosphaadamantan-6-yllithium (PTA-Li) resulted in the formation of a series of slightly water-soluble beta-phosphino alcohols (PTA-CRR'OH, R = C6H5, C(6)H(4)OCH(3), ferrocenyl; R' = H, C(6)H(5), C(6)H(4)OCH(3)) derived from the heterocyclic phosphine PTA. Insertion of CO(2) yielded the highly water-soluble carboxylate PTA-CO(2)Li, S(2)5 degrees approximately 800 g/L. The compounds have been fully characterized in the solid state by X-ray crystallography and in solution by multinuclear NMR spectroscopy. The addition of PTA-Li to symmetric ketones results in a racemic mixture of PTA-CR(2)OH ligands with a single resonance in the (31)P{(1)H} NMR spectrum between -95 and -97 ppm. The addition of PTA-Li to aldehydes results in a mixture of diasteromeric compounds, PTA-CHROH, with two (31)P{(1)H} NMR resonances between -100 and -106 ppm. Three (eta(6)-arene)RuCl(2)(PTA-CRR'OH) complexes of these ligands were synthesized and characterized, with the ligands binding in a kappa1 coordination mode. All the ligands and ruthenium complexes are slightly soluble in water with S25 degrees = 3.9-11.1 g/L for the PTA-CRR'OH ligands and S(25) degrees = 3.3-14.1 g/L for the (eta(6)-arene)RuCl(2)(PTA-CRR'OH) complexes.

Rh‐TPPTS intercalated layered double hydroxides as hydroformylation catalyst

AbstractTrans‐RhCl(CO)(TPPTS)2 [TPPTS, trisodium salt of tri‐(m‐sulfophenyl)‐phosphine] and TPPTS ligands have been cointercalated into zinc–aluminum‐layered double hydroxides (ZnAl‐LDHs) by in situ complexation, and the catalytic performances of the resulting materials for 1‐hexene hydroformylation have been investigated. The intercalated materials were characterized by means of XRD, FTIR, ICP, and 31P MAS NMR. The rhodium complex and TPPTS ligands coexist in the interlayer galleries of LDH (denoted as RhP2‐P‐ZnnAl‐LDH, where n denotes as the molar ratio Zn/Al), with an interlayer spacing of ca. 1.58 nm. Compared with the catalytic properties of the corresponding water‐oil biphasic catalyst under similar reaction conditions, RhP2‐P‐Zn3Al‐LDH showed better reusability and activity. Furthermore, compared with a related material prepared by ion exchange, the RhP2‐P‐Zn3Al‐LDH showed better activity and selectivity towards aldehyde. The influence of the Zn/Al molar ratio in RhP2‐P‐ZnnAl‐LDH has also been studied, and it was found that higher selectivity to aldehydes and lower activity were obtained with increasing Zn/Al molar ratio. © 2007 American Institute of Chemical Engineers AIChE J, 2007

Heterogeneous hydrogenation of bicyclo[2.2.2]octenes on Rh/TPPTS/LDH catalysts

The Rh-TPPTS complex was heterogenized onto layered double hydroxides (LDH) Zn 3AlCl and Co 2FeCO 3 using ion-exchange procedure. Before ion exchange, the Rh precursor [Rh(cod)Cl] 2 was dissolved together with the TPPTS ligand in deionised water and stirred for 12 h. After stirring, the LDH was added to the solution and stirred for another 24 h, then filtered, washed with deionised water, and dried under vacuum at room temperature for 16 h. The characterization of the catalysts was carried out using several techniques: ICP-AES, N 2 adsorption–desorption isotherms at −196 °C, thermal analysis, powder X-ray diffraction, XPS and DRIFTs. Substrates were prepared via Diels–Alder reaction of various 2 H-pyran-2-ones with N-substituted maleimides in an aqueous medium with microwave irradiation. The catalytic tests were performed in a stirred stainless-steel autoclave using H 2 pressures in the range 20–40 atm, 30 mg catalyst and 30 mg substrate, at different temperatures. Hydrogenation of bicyclo[2.2.2]octenes showed that these strained and functionalized cycloadducts were inert to classic catalysts but could be hydrogenated by using ionic-immobilized Rh-ligand complexes on the LDH. The Rh-TPPTS/Zn 3AlCl was found to exhibit a pretty high activity and selectivity for such reactions leading to heteropolycyclic derivatives. The heterogeneous catalyst was easily recycled with no leaching.

Two new water-soluble derivatives of 1,3,5-triaza-7-phosphaadamantane (PTA): Synthesis, characterization, X-ray analysis and solubility studies of 3,7-diformyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane and 1-pyridylmethyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane bromide

Two water-soluble phosphines, 3,7-diformyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane ( 1, DFPTA) and 1-pyridylmethyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane bromide ( 2, [pymePTA]Br), have been respectively, prepared by reacting 1,3,5-triaza-7-phosphaadamantane (PTA) with formic anhydride and bromomethylpyridine. Compound 1 is only the second acyl derivative of PTA to be prepared while 2 is only the second derivative of PTA reported that contains an aromatic appendage. Both compounds were characterized by elemental analysis, FAB-MS, 1H, 13C, and 31P NMR spectroscopy, and single crystal X-ray diffraction. This analysis showed that the formamide groups of 1 were in an anti confirmation in solution but in a syn confirmation in the solid state. The solubilities of 1 and 2 were examined in common organic solvents and water. It was found that 1.1 M aqueous solutions of 1 could be prepared while 2.4 M solutions of 2 were produced. The greater solubility of 2 was likely due to its ionic nature.

Organometallic Supramolecular Mixed-Valence Cobalt(I)/Cobalt(II) Aquo Complexes Stabilized with the Water-Soluble Phosphine Ligandp-TPPTP (p-triphenylphosphine triphosphonic acid)

Reaction of the water-soluble phosphine phosphonic acid p-TPPTP(H)6 (p-triphenylphosphine triphosphonic acid) with Co2(CO)8 under biphasic conditions results in the formation of Co6(CO)3(p-TPPTP)2(H2O)24·24H2O (2) or Co4(CO)3(p-TPPTP)2(H2O)24·24H2O (3) depending on the pH of the solution. These supramolecular organometallic Co(I)/Co(II) complexes contain either six (2) or four (3) crystallographically distinct cobalt ions. The cation [Co(CO)3(p-TPPTP)2]+ from 2 was reacted with titanium tetraisopropoxide via a sol−gel method to give a titania-supported Co(I) olefin hydroformylation catalyst, which was characterized using solid-state 31P NMR, IR, and XPS.

Homogenous Catalysis with Gold: Efficient Hydration of Phenylacetylene in Aqueous Media

A variety of gold(I) complexes containing the water-soluble phosphine ligands TPPMS, TPPDS, and TPPTS (mono-, di-, and tri-sulfonated triphenylphosphine, respectively) were tested as catalysts for the hydration of phenylacetylene in aqueous media. The gold(I) alkynyl complexes [AuC⋮CR(TPPTS)] (where R = tBu and 3-thiophenyl) give the highest ever reported turnover frequencies (1000 and 1060 h-1, respectively) for the hydration of phenylacetylene under optimum conditions (0.1 mol % catalyst loading, 10 mol % H2SO4, 1 h reflux in 5:1 MeOH/H2O). The hydration of phenylacetylene can also be carried out using only water and reaction medium, which allows recycling of the gold catalyst without significant drop of activity for at least three cycles. DFT calculations were used to compare relative energies of possible intermediates involved in the catalytic cycle.

Water-soluble and water-stable Gold(I), Gold(II) and Gold(III) phosphine complexes: The early years

This article briefly reviews the still rather limited knowledge of the chemistry, structures, reactions and applications of gold complexes containing water-soluble phosphine ligands sorted by gold oxidation state.