Water-soluble Phosphane Research Articles

Ligand and Gold(I) Fluorescein-AIEgens as Photosensitizers in Solution and Doped Polymers.

The synthesis of fluorescein propargyl diether (L) and two different dinuclear gold(I) derivatives containing a water-soluble phosphane [1,3,5-triaza-7-phosphatricyclo[3.3.1.13.7]decane (PTA) for complex 1 and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) for complex 2] has been successfully performed. All compounds display intrinsic emission from fluorescein, being less intense for gold(I) complexes due to the heavy-atom effect. All compounds aggregate in acetonitrile/water mixtures with the formation of larger aggregates for those samples containing more water content, as evidenced by dynamic light scattering and small-angle X-ray scattering experiments, in agreement with the absorption and emission data. The emission of the samples increases when they are used to obtain luminescent materials with four different organic matrices [poly(methyl methacrylate, polystyrene (PS), cellulose, and Zeonex]. The compounds display very high values of singlet oxygen (1O2) production in dichloromethane. Singlet oxygen production was also evaluated in the doped matrices, being the highest in PS and with an exciting increase on PS microspheres. Density functional theory (BP86-D3) and GFN2-xTB calculations were used to model the assembly of L and complexes 1 and 2 with the different organic matrices and rationalize the experimental findings based on the geometries, molecular electrostatic potential surfaces, and complementarity and HOMO-LUMO gaps.

Comprehensive Investigation of the Photophysical Properties of Alkynylcoumarin Gold(I) Complexes.

Six gold(I) complexes (R3P-Au-Coum) containing three different alkynylcoumarin chromophores (Coum) with different electron-donating and electron-withdrawing characteristics and two different water-soluble phosphanes (PR3 = PTA (a) and DAPTA (b)) have been synthesized (1a,b, unsubstituted coumarin; 2a,b, 4-methyl substituted coumarin; 3a,b, 3-chloro and 4-methyl substituted coumarin). A comprehensive study of the photophysical properties of the R3P-Au-Coum, together with their propynyloxycoumarin precursors 1-3, was performed in solution at room and low temperatures. Spectral and photophysical characteristics of the R3P-Au-Coum essentially depend on the electronic characteristics of the propynyloxycoumarin ligand. The presence of the Au(I) atom was found to be responsible for an increase of the intersystem crossing, with triplet state quantum yield values, ϕT, ranging from ∼0.05 to 0.35 and high coumarin phosphorescence quantum yield values for derivatives 1 and 2; fluorescence dominates the deactivation in derivatives 3. Efficient singlet oxygen photosensitization was observed for the new compounds 3a,b. From TDDFT calculations, the relevant HOMO and LUMO of the compounds, i.e., those involved in the transitions, are dominated by the frontier orbitals associated with the coumarin core. The Au(I)-phosphane structure introduces a new transition assigned to an intraligand transition involving the phosphane ligand, and π(C≡C) system, to the p orbitals of phosphorus and gold atoms.

CpRu Complexes Containing Water Soluble Phosphane PTA and Natural Purines Adenine, Guanine and Theophylline: Synthesis, Characterization, and Antiproliferative Properties

Complexes [RuCp(Adeninate‐κN9)(PTA)2] (1), [RuCp(Guaninate‐κN9)(PTA)2] (2), [RuCp(Theophyllinate‐κN7)(PTA)2] (3), [RuCp(Adeninate‐κN9)(PPh3)(PTA)] (4), [RuCp(Guaninate‐κN9)(PPh3)(PTA)] (5) and [RuCp(Theophyllinate‐κN7)(PPh3)(PTA)] (6) were synthesized and characterized by NMR spectroscopy, elemental analysis and FT‐IR (PTA = 1,3,5‐triaza‐7‐phosphaadamantane). Crystal structures of 1·H2O·3EtOH, 3·CH3COCH3 and 4·H2O were also determined by single‐crystal X‐ray diffraction. The antiproliferative activities of the complexes against cisplatin‐sensitive T2 and cisplatin‐resistant SKOV3 cell lines have also been evaluated. Theoretical studies were preformed to elucidate how the adeninate ligand is coordinated to the metal.

Palladium(II) and Platinum(II) Complexes of Novel Water-Soluble Phosphane CAP: Structure, Interligand Hydrogen-Hydrogen Bonding and in Vitro Cytotoxicity

Palladium(II) and platinum(II) chloro complexes of novel water-soluble cage-like phosphane CAP (1,4,7-triaza-9-phosphatricyclo[5.3.2.14,9]tridecane) have been synthesized and characterized in comparison with their counterparts bearing well known PTA (1,3,5-triaza-7-phosphaadamantane) ligand. A peculiar structural feature of studied cis-[MCl2L2] complexes is the occurrence of interligand C−Hσ+⋅⋅⋅σ+H−C interactions (hydrogen-hydrogen bonds) between the phosphane cages: the first case encountered so far among metal-phosphane complexes. Due to substantial stabilizing contribution to the net molecular energy of the complexes (∼ 20 kcal mol−1), hydrogen-hydrogen bonding is sufficient to maintain sterically overcrowded cis conformations of the complexes. The interplay between protonation stage of the ligands and their conformations can be a reason of significant differences in in-vitro cytotoxicity between CAP complexes and their PTA-bearing counterparts.

Transition Metal Complexes Coordinated by Water Soluble Phosphane Ligands: How Cyclodextrins Can Alter the Coordination Sphere?

The behaviour of platinum(II) and palladium(0) complexes coordinated by various hydrosoluble monodentate phosphane ligands has been investigated by 31P{1H} NMR spectroscopy in the presence of randomly methylated β-cyclodextrin (RAME-β-CD). This molecular receptor can have no impact on the organometallic complexes, induce the formation of phosphane low-coordinated complexes or form coordination second sphere species. These three behaviours are under thermodynamic control and are governed not only by the affinity of RAME-β-CD for the phosphane but also by the phosphane stereoelectronic properties. When observed, the low-coordinated complexes may be formed either via a preliminary decoordination of the phosphane followed by a complexation of the free ligand by the CD or via the generation of organometallic species complexed by CD which then lead to expulsion of ligands to decrease their internal steric hindrance.

Novel metalloantimalarials: Transmission blocking effects of water soluble Cu(I), Ag(I) and Au(I) phosphane complexes on the murine malaria parasite Plasmodium berghei

The water soluble phosphane complexes [M(L)4]PF6 (M=Cu(I), Ag(I)) and [Au(L)4]Cl (L=thp (tris(hydroxymethyl)phosphane) or PTA (1,3,5-triaza-7-phosphaadamantane)) showed notable in vitro activity against Plasmodium early sporogonic stages, the sexual forms of the malaria parasite that are responsible for infection of the mosquito vector. Effects varied according to both, the type of metal and phosphane ligands. [Ag(thp)4]PF6 was the best performing complex exhibiting a half inhibitory concentration (IC50) value in the low micromolar range (0.3–15.6μM). The silver complex [Ag(thp)4]PF6 was characterized by X-ray crystallography revealing that the structure comprises the cationic complex [Ag(thp)4]+, the PF6− anion, and a water molecule of crystallization. Our results revealed that Cu(I), Ag(I) and Au(I) phosphanes complexes elicited similar activity profiles showing potential for the development of antimalarial, transmission blocking compounds. Molecules targeting the sexual parasite stages in the human and/or mosquito host are urgently needed to complement current artemisinin based treatments and next generation antimalarials in a vision not only to cure the disease but to interrupt its transmission.

Easy synthesis and water solubility of ruthenium complexes containing PPh3, mTPPMS, PTA and mPTA, (mTPPMS = meta-triphenyphosphine monosulfonate, PTA = 1,3,5-triaza-7-phosphaadamantane, mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane)

New water soluble {CpRu} complexes with formula [RuCpX(L1)(L2)]n+ (L1, L2=PPh3, mTPPMS (meta-triphenyphsphine monosulfonate), PTA (1,3,5-triaza-7-phosphaadamantane), mPTA (N-methyl-1,3,5-triaza-7-phosphaadamantane)) were synthesized and characterized by elemental analytical, IR and NMR spectroscopy. Complexes [RuClCp(PPh3)(mPTA)](OTf) (3·OTf), [RuCpI(PPh3)(mPTA)]·2I·EtOH (5·I·EtOH)·and [RuCpBr(PTA)2]·3.5H2O (6·3.5H2O) were also characterized by single crystal X-ray diffraction. The NMR spectra of the complexes are in agreement with their composition, indicating also that their solid state structure is maintained in solution. These results are integrated in a thorough overview of preparative routes, structural composition and solubility of {CpRu} complexes containing water-soluble phosphanes.

Study of the effect of the chromophore and nuclearity on the aggregation and potential biological activity of gold(I) alkynyl complexes

The synthesis and characterization of four organometallic gold(I) complexes containing different water soluble phosphanes (TPPTS, PTA and DAPTA) and chromophoric units (4-pyridylethynyl and propargyloxycoumarin) is here reported. The analysis of their absorption and emission spectra led us to attribute their luminescent behavior to the chromophoric organic ligands. Moreover, the presence of the gold(I) metal atom has been observed to be the responsible of an efficient intersystem crossing process responsible for the observed phosphorescence emission. Broad emission bands are observed in most cases due to the formation of organized aggregates in solution in agreement with microscopic characterization.Biological activity of the complexes showed very low effects against tumor cell growth but an inhibitory potency against thioredoxin reductase (TrxR). The missing/low cytotoxic effects could be related to a low bioavailability as determined by atomic absorption spectroscopy.

In vitro and in vivo evaluation of organometallic gold(I) derivatives as anticancer agents.

Alkyne gold(I) derivatives with the water soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane) and DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) were described and their anticancer potential against the colon cancer cell line Caco-2 (PD7 and TC7 clones) was studied. Strong antiproliferative effects are found, for all the new complexes, to be even more pronounced than for the reference drug cisplatin, and similar to auranofin. The interaction of these derivatives with bovine serum albumin (BSA) was studied by fluorescence spectroscopy. The types of quenching and binding constants were determined by a fluorescence quenching method. Moderate values of the binding constants are calculated for the tested derivatives indicating that these complexes can be stored and carried easily by this protein in the body. The study of the thermodynamic parameters in the case of [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] points out to the presence of van der Waals interactions or hydrogen bonding between the metallic complex and the protein. In addition, the complex [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] has shown inhibition in colon cancer proliferation of HTC-116-luc2 cell lines via the apoptotic pathway and S-phase arrest of the cell cycle. Intraperitoneal injection of this derivative in athymic nude mice inoculated with HTC-116-luc2 cells prolonged their survival and displayed moderate inhibition of the tumour growth with no subsequent organ (kidney and liver) damage after treatment.

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis.

New cyclodextrin (CD)-grafted polymers functionalized with water-soluble phosphanes were synthesized in three steps starting from polyNAS. Once characterized by NMR spectroscopy and size-exclusion chromatography, they were used as additives in Rh-catalyzed hydroformylation of 1-hexadecene. The combined supramolecular and coordinating properties of these polymers allowed increasing the catalytic activity of the reaction without affecting the selectivities.

Rhodium catalyzed hydroformylation assisted by cyclodextrins in biphasic medium: Can sulfonated naphthylphosphanes lead to active, selective and recyclable catalytic species?

New sulfonated naphthylphosphanes having an average sulfonation degree around 2 have been synthetized and tested as ligand in the aqueous biphasic Rh-catalyzed hydroformylation of 1-decene assisted by randomly methylated β-cyclodextrins. All these water-soluble phosphanes associated to a rhodium precursor were able to perform aqueous hydroformylation of 1-decene. The best results in terms of catalyst recovery and recycling were obtained with sulfonated 2-naphthylphosphanes. With sulfonated 1-naphthylphosphanes, formation of low-coordinated catalytic species leading to a catalyst leaching in the organic phase was postulated. These results were rationalized by considering that sulfonated 1-naphthylphosphanes are bulkier ligands than sulfonated 2-naphthylphosphanes.

S-Propargylthiopyridine Phosphane Derivatives As Anticancer Agents: Characterization and Antitumor Activity

S-Propargylthiopyridine phosphane gold(I) derivatives with the water-soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), and TPPTS (sodium triphenylphosphane trisulfonate) are described and used as metalloligands by coordination to copper(I). New heteronuclear gold(I) and copper(I) complexes of the type [Au2Cu(C≡CCH2SC5H4N)2L2] (L = PTA, DAPTA, PPh3, TPPTS) and [AuCu(C≡CCH2SC5H4N)(L)(PPh3)2]NO3 (L = PTA, DAPTA) are reported. The X-ray crystal structure of [Au(C≡CCH2SC5H4N)(PTA)] (1), which confirms the coordination of the metallic center to the alkyne unit, displays a zigzag polymeric chain with short gold–gold contacts of 3.2680(16) Å. Strong antiproliferative effects are found for most of the new complexes in human colon cancer cell lines (Caco-2, PD7, and TC7 clones), with these effects being more pronounced than for the reference drugs cisplatin and auranofin, especially for the heterodimetallic derivatives, which are markedly more active than the corresponding mononuclear precursors. Apoptosis-induced cell death is found for all compounds, as shown by an annexin-V/propidium iodide double-staining assay.

Trans-Thionate Derivatives of Pt(II) and Pd(II) with Water-Soluble Phosphane PTA and DAPTA Ligands: Antiproliferative Activity against Human Ovarian Cancer Cell Lines

A series of PTA and DAPTA platinum(II) and palladium(II) thionate complexes of the type trans-[M(SN)2P2] were prepared from the reaction of cis-[MCl2P2] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with the in situ generated sodium salts of the heterocyclic thiones S-m-methylpyrimidine-2-thione, S-4,6-dimethylpyrimidine-2-thione, S-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, S-1,3,4,-thiadiazole-2-thione, S-4,5-H-thiazolan-2-thione, and S-pyrimidine-4(1H)-one-2-thione. The X-ray structures of six of the compounds confirm the trans disposition and, only in the case of [Pd2Cl2(S-pyrimidine-4(1H)-one-2-thionate)2(PTA)2], a dinuclear structure with a Pd-Pd distance of 3.0265(14)Å was observed. In vitro cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC50) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines.

Synthesis and Structural Features of New Ruthenium(II) Complexes Containing the Scorpionate Ligands Tris(pyrazol‐1‐yl)methanesulfonate (Tpms) and Tris(pyrazol‐1‐yl)methane (Tpm)

AbstractNew ruthenium(II) scorpionate complexes containing tris(pyrazol‐1‐yl)methanesulfonate (Tpms) and tris(pyrazol‐1‐yl)methane (Tpm) ligands have been synthesized. For complexes with Tpms, two isomers are obtained as the kinetic (1a) and thermodynamic (1b) products, which shows that, for these complexes, the κ3(N,N,N) coordination mode of the Tpms ligand is favored over κ3(N,N,O) coordination. In addition, complexes with water soluble phosphane ligands 1,3,5‐triaza‐7‐phosphatricyclo[3.3.1.13,7]decane (PTA) and 1‐alkyl‐3,5‐diaza‐1‐azonia‐7‐phosphatricyclo[3.3.1.13,7]decane (1‐R‐PTA) have been prepared and structurally characterized.

Thiolato gold(i) complexes containing water-soluble phosphane ligands: a characterization of their chemical and biological properties

A series of thiolate gold(I) derivatives bearing water soluble phosphanes--namely sodium triphenylphosphane monosulfonate (TPPMS), sodium triphenylphosphane trisulfonate (TPPTS), 1,3,5-triaza-7-phosphaadamantane (PTA) and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)--is reported and the compounds studied for their luminescence properties in the solid state. Two of these derivatives, [Au(SMe(2)pyrim)(PTA)] and [Au(SBenzoxazole)(DAPTA)], are also structurally characterized by X-ray diffraction analysis. Strong antiproliferative effects are observed for most of the compounds in the human ovarian carcinoma cell lines (A2780/S) and its cisplatin-resistant variant (A2780/R), which depend on both the type of thiolate and phosphane ligands. ICP-MS studies were also performed to evaluate the influence of the gold uptake on the cytotoxic potency of the compounds.

Antitumor activity of new hydridotris(pyrazolyl)borate ruthenium(ii) complexes containing the phosphanes PTA and 1-CH3–PTA

The synthesis and full characterization of new half-sandwich ruthenium(II) complexes containing κ(3)(N,N,N)-hydridotris(pyrazolyl)borate (κ(3)(N,N,N)-Tp) and the water-soluble phosphanes 1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]decane (PTA) and 1-methyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane (1-CH(3)-PTA) has been explored. Single crystal X-ray diffraction analysis for complex [RuCl{κ(3)(N,N,N)-Tp}(PMe(2)Ph)(1-CH(3)-PTA)][CF(3)SO(3)]·2NCMe is also reported. DNA binding properties of the ruthenium complexes have been evaluated by mobility shift assay and MALDI-TOF mass spectrometry. The in vitro antitumor activity of these compounds was assessed by examining their ability to inhibit cell proliferation in a number of human cancer cell lines (NCI-H460, SF-268, MCF-7) and non-tumor human umbilical vein endothelial cells (HUVEC). Some of these new compounds show promising cytotoxic activity with IC(50) values in the low micromolar range, and display differential effects on cancer and normal cell growth.

Amphiphilic photo-isomerisable phosphanes for aqueous organometallic catalysis

Water-soluble phosphanes were tagged with a light-responding diazo group. Upon UV exposure, the diazo-isomerisation led to phosphane morphology change, resulting in an increase in the reaction rate of an aqueous palladium-catalysed cleavage reaction.

Alkyne activation by half-sandwich ruthenium(II) complexes bearing the water-soluble phosphane 1,3,5-triaza-7-phosphaadamantane (PTA)

Complex [RuCl{ κ 3( N, N, N)-Tp}(PPh 3)(PTA)] ( κ 3( N, N, N)-Tp = hydridotris(pyrazolyl)borate) containing the water-soluble phosphane 1,3,5-triaza-7-phosphatricyclo[3.3.1.1 3,7]decane (PTA) reacts with terminal alkynes producing to the corresponding neutral alkynyl complexes [Ru(C CR){ κ 3( N, N, N)-Tp}(PPh 3)(PTA)] (R = Ph ( 1a), n Bu ( 1b), 1-cyclopentenyl ( 1c), p-methoxyphenyl ( 1d), 6-methoxynaft-2-yl ( 1e)). When halide is extracted from complex [RuCl{ κ 3( N, N, N)-Tp}(PPh 3)(PTA)] followed by treatment with propargyl alcohols, the corresponding allenylidene complexes [Ru{ κ 3( N, N, N)-Tp}(PPh 3)(PTA)(C C CPh 2)][X] (X = PF 6 ( 2a), CF 3SO 3 ( 2b)) and [Ru{ κ 3( N, N, N)-Tp}(PPh 3)(PTA)(C C CC 12H 8)][PF 6] ( 3) result. Electrophilic attack on the complexes thus obtained leads chemoselectively to the alkynyl complexes [Ru(C CR){ κ 3( N, N, N)-Tp}(PPh 3)(1-CH 3-PTA)][CF 3SO 3] (R = Ph ( 4a), n Bu ( 4b), and 1-cyclopentenyl ( 4c)) and to the dicationic allenylidene complexes [Ru{ κ 3( N, N, N)-Tp}(PPh 3)(1-H-PTA)(C C CC 12H 8)][PF 6] 2 ( 5) and [Ru{ κ 3( N, N, N)-Tp}(PPh 3)(1-CH 3-PTA)(C C CPh 2)][CF 3SO 3] 2 ( 6).

Unexpected Coordination Modes of the Tris(imidazolyl)phosphane Oxide Ligand 4‐TIPOiPr in the Chloro Complexes of Zinc, Cobalt and Nickel

AbstractThe coordination chemistry of the water soluble phosphane oxide ligand tris[2‐isopropylimidazol‐4(5)‐yl]phosphane oxide, 4‐TIPOiPr, has been explored. A variety of 3d‐metal halide complexes have been prepared and the crystal structures of the solvates [(4‐TIPOiPr)ZnCl2]·MeOH·1/2dioxane (1·MeOH·1/2dioxane), [(4‐TIPOiPr)CoCl2]·H2O·2dioxane (2·H2O·2dioxane) and [(4‐TIPOiPr)2Ni(MeOH)2]Cl2·2MeOH (3·2MeOH) have been determined. All three structures show unprecedented coordination modes of the 4‐TIPOiPr ligand. Both zinc and cobalt complexes are coordinated in a bidentate κ2N fashion, whereas the nickel atom is coordinated by two ligands in a κN,O mode using one imidazolyl substituent and the P=O oxygen atom.

Novel hydridotris(pyrazolyl)borate ruthenium(II) complexes containing the water-soluble phosphane 1,3,5-triaza-7-phosphaadamantane: Synthesis and evaluation of DNA binding properties

A series of half-sandwich ruthenium(II) complexes containing κ 3( N, N, N)-hydridotris(pyrazolyl)borate (κ 3( N, N, N)-Tp) and the water-soluble phosphane 1,3,5-triaza-7-phosphaadamantane (PTA) [RuX{κ 3( N, N, N)-Tp}(PPh 3) 2− n (PTA) n ] ( n = 2, X = Cl ( 1), n = 1, X = Cl ( 2), I ( 3), NCS ( 4), H ( 5)) and [Ru{κ 3( N, N, N)-Tp}(PPh 3)(PTA)L][PF 6] (L = NCMe ( 6), PTA ( 7)) have been synthesized. Complexes containing 1-methyl-3,5-diaza-1-azonia-7-phosphaadamantane(m-PTA) triflate [RuCl{κ 3( N, N, N)-Tp}(m-PTA) 2][CF 3SO 3] 2 ( 8) and [RuX{κ 3( N, N, N)-Tp}(PPh 3)(m-PTA)][CF 3SO 3] (X = Cl ( 9), H ( 10)) have been obtained by treatment, respectively, of complexes 1, 2 and 5 with methyl triflate. Single crystal X-ray diffraction analysis for complexes 1, 2 and 4 have been carried out. DNA binding properties by using a mobility shift assay and antimicrobial activity of selected complexes have been evaluated.