Triphenylphosphane Ligands Research Articles

Anticancer Activity of Imidazolyl Gold(I/III) Compounds in Non-Small Cell Lung Cancer Cell Lines.

Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight structurally related gold(I) and gold(III) complexes with NHC and halides or triphenylphosphane ligands were investigated as lung cancer cell growth inhibitors. As expected, gold compounds with PPh3 were found to be more cytotoxic than homoleptic [(NHC)2-Au(I)]X or heteroleptic NHC-Au(I)X or NHC-Au(III)X3 complexes. Mixed ligand gold(I) compounds exhibiting the linear NHC-AuPPh3 (compound 7) or the trigonal NHC-Au(Cl)PPh3 (compound 8) arrangements at the central metal were found to be the best lung cancer cytotoxic compounds. Analysis of the TrxR residual activity of the treated cells revealed that these compounds efficiently inhibit the most accredited molecular target for gold compounds, the TrxR, with compound 8 reaching more than 80% activity reduction in lung cells. Some of the current cancer lung therapy protocols consist of specific lung cancer cell cytotoxic agents combined with antifolate drugs; interestingly, the herein gold compounds are both TrxR and antifolate inhibitors. The human DHFR was inhibited with IC50 ranging between 10-21 µM, depending on substrate concentrations, proceeding by a likely allosteric mechanism only for compound 8.

(4-Butyl-1-ethyl-1,2,4-triazol-5-ylidene)[(1,2,5,6-η)-cycloocta-1,5-diene](triphenylphosphane)iridium(I) tetrafluoridoborate

The title compound, [Ir(C8H12)(C8H15N3)(C18H15P)]BF4, a new triazole-based N-heterocyclic carbene iridium(I) cationic complex with a tetrafluoridoborate counter-anion, crystallizes with two cations and two anions in the asymmetric unit of space group Pc. The Ir centers of the cations have distorted square-planar conformations, formed by a bidentate (η2 + η2) cycloocta-1,5-diene (COD) ligand, an N-heterocyclic carbene and a triphenylphosphane ligand with the NHC carbon atom and P atom being cis. In the extended structure, non-classical C–H...F hydrogen bonds, one of which is notably short (H...F = 2.21 Å), link the cations and anions. The carbon atoms of one of the COD ligands are disordered over adjacent sites in a 0.62:0.38 ratio.

(1,2,5,6-η)-Cyclo-octa-1,5-diene](1-ethyl-4-isopropyl-1,2,4-triazol-5-yl-idene)(tri-phenylphos-phane)iridium(I) tetra-fluorido-borate di-chloro-methane sesquisolvate.

The synthesis and crystal structure of a new triazole-based N-heterocyclic carbene iridium(I) cationic complex with a tetra-fluorido-borate counter-anion and solvating di-chloro-methane, [Ir(C8H12)(C7H13N3)(C18H15P)]BF4·1.5CH2Cl2, is reported. The IrI center of the cationic complex has a distorted square-planar conformation, formed by a bidentate cyclo-octa-1,5-diene (COD) ligand, an N-heterocyclic carbene, and a triphenylphosphane ligand. There are weak hydrogen-bonding inter-actions between C-H groupings of the iridium complex and F atoms of the [BF4]- counter-ions. The atoms of the COD ligand are disordered over two sets of sites in a 0.65:0.35 ratio and two of the F atoms of the anion are disordered over adjacent sites in a 0.6:0.4 ratio. One of the di-chloro-methane solvent mol-ecules is disordered about an inversion center with 0.5 occupancy.

(1,2,5,6-η)-Cyclo-octa-1,5-diene](4-isopropyl-1-methyl-1,2,4-triazol-5-yl-idene)(tri-phenyl-phos-phane)iridium(I) tetra-fluorido-borate di-chloro-methane 0.8-solvate.

A new triazole-based N-heterocyclic carbene iridium(I) cationic complex with a tetra-fluorido-borate counter-anion, [Ir(C8H12)(C18H15P)(C6H11N3)]BF4·0.8CH2Cl2, has been synthesized and structurally characterized. The central IrI atom of the cationic complex has a distorted square-planar coordination environment, formed by a bidentate cyclo-octa-1,5-diene (COD) ligand, an N-heterocyclic carbene, and a tri-phenyl-phosphane ligand. The crystal structure comprises C-H⋯π(ring) inter-actions that orient the phenyl rings; non-classical hydrogen-bonding inter-actions between the cationic complex and the tetra-fluorido-borate anion are also present. The complex crystallizes in a triclinic unit cell with two structural units and an incorporation of di-chloro-methane solvate mol-ecules with an occupancy of 0.8.

Synthesis and crystal structures of silver(I) halide complexes containing 1,3-diisopropyl-2-thiourea and triphenylphosphane ligands

Synthesis and crystal structures of silver(I) halide complexes containing 1,3-diisopropyl-2-thiourea and triphenylphosphane ligands

Synthesis and crystal structures of metal(I) bromide complexes containing 4-phenylthiosemicarbazide and triphenylphosphane ligands

Synthesis and crystal structures of metal(I) bromide complexes containing 4-phenylthiosemicarbazide and triphenylphosphane ligands

Re(V) complexes containing the phenylimido (NPh2−) core and SNS-thiosemicarbazide ligands

Reactions of thiosemicarbazone ligands (H2L1) with [ReX3(NPh)(PPh3)2] (X = Cl or Br) led to the formation of stable rhenium(V) complexes of composition [ReX(NPh)(HL1)(PPh3)]X. The Re(V) complexes have been characterized by diverse techniques including FTIR, 1H and 31P NMR, elemental analysis, HRMS and single-crystal X-ray diffraction analysis. The crystal structures of the complexes rhenium complexes showed the formation a distorted octahedron environment around the Re(V) metal center, with the axial positions being occupied by the halogen atom and by the nitrogen atom from the phenylimido moiety, while the equatorial positions are occupied by the S,N,S-thiosemicarbazonate and the triphenylphosphane ligands. Furthermore, the “3 + 2” mixed ligand complex [Re(NPh)(L1b)(Et2btu)], where HEt2btu is N,N-diethyl-N’-benzoylthiourea, could be obtained from an equimolar reaction of [ReCl(NPh)(HL1)(PPh3)]Cl with the bidentate thiourea in the presence of NEt3. Finally, DFT calculations were applied in order to propose a complex suitable for biocouplings upon substitution of a NH2 group at the 4-position of the phenylimido ligand in [Re(NPh)(L1b)(Et2btu)]. The compounds studied here represent the first examples of phenilimidorhenium(V) complexes with thiosemicarbazones.

Ruthenium-Cyclopentadienyl Bipyridine-Biotin Based Compounds: Synthesis and Biological Effect.

Prospective anticancer metallodrugs should consider target-specific components in their design in order to overcome the limitations of the current chemotherapeutics. The inclusion of vitamins, which receptors are overexpressed in many cancer cell lines, has proven to be a valid strategy. Therefore, in this paper we report the synthesis and characterization of a set of new compounds [Ru(η5-C5H5)(P(C6H4R)3)(4,4'-R'-2,2'-bpy)]+ (R = F and R' = H, 3; R = F and R' = biotin, 4; R = OCH3 and R' = H, 5; R = OCH3 and R' = biotin, 6), inspired by the exceptional good results recently obtained for the analogue bearing a triphenylphosphane ligand. The precursors for these syntheses were also described following modified literature procedures, [Ru(η5-C5H5)(P(C6H4R)3)2Cl], where R is -F (1) or -OCH3 (2). The structure of all compounds is fully supported by spectroscopic and analytical techniques and by X-ray diffraction studies for compounds 2, 3, and 5. All cationic compounds are cytotoxic in the two breast cancer cell lines tested, MCF7 and MDA-MB-231, and much better than cisplatin under the same experimental conditions. The cytotoxicity of the biotinylated compounds seems to be related with the Ru uptake by the cells expressing biotin receptors, indicating a potential mediated uptake. Indeed, a biotin-avidin study confirmed that the attachment of biotin to the organometallic fragment still allows biotin recognition by the protein. Therefore, the biotinylated compounds might be potent anticancer drugs as they show cytotoxic effect in breast cancer cells at low dose dependent on the compounds' uptake, induce cell death by apoptosis and inhibit the colony formation of cancer cells causing also less severe side effects in zebrafish.

{(Hydrogen 2,2′,2′′-boranetriyl)tris[6-tert-butyl-4-methylpyridazine-3(2H)-thione]-κ3H,S,S′}(triphenylphosphane-κP)copper(I) chloroform disolvate

In the title complex, [Cu(C27H40BN6S3)(C18H15P)]·2CHCl3, the CuIatom is surrounded in a trigonal-planar arrangement by the triphenylphosphane ligand and two of the three S atoms of the scorpionate ligand with an additional 3-center–2-electron B—H...Cu interaction, with the H atom as the apex of a pyramid [B—H = 1.140 (17) Å and Cu—H = 1.826 (16) Å].

(Thiocyanato-κS)tris(triphenylphosphane-κP)silver(I)

In the mononuclear title complex, [Ag(SCN)(C18H15P)3], the AgIcenter is in a slightly distorted tetrahedral coordination geometry formed by one S atom from a terminal thiocyanate ligand and three P atoms from three triphenylphosphane ligands. In the crystal, weak C—H...N hydrogen bonds connect molecules into a two-dimensional network parallel to (10\overline{1}). One of the phenyl rings is disordered over two positions which were refined with an occupancy ratio of 0.715 (16):0.285 (16).

Crystal structure of [N,N-bis-(di-phenyl-phospho-ro-thio-yl)amidato-κ2S,S']bis-(tri-phenyl-phosphane-κP)copper(I) di-chloro-methane monosolvate.

The title compound, [Cu(C24H20NP2S2)(C18H15P)2]·CH2Cl2 or [Cu(dppaS2)(PPh3)2]·CH2Cl2, is a neutral mononuclear copper(I) complex bearing an N,N-bis-(di-phenyl-phospho-rothio-yl)amidate (dppaS2-) ligand and two tri-phenyl-phosphane ligands. The molecular structure shows that the two S atoms of the dppaS2- ligand [Cu-S = 2.3462 (9) and 2.3484 (9) Å] and the two P atoms of the two tri-phenyl-phosphane ligands [Cu-P = 2.3167 (9) and 2.2969 (9) Å] coordinate to the copper(I) atom, resulting in a tetra-hedral coordination geometry. The crystallographically observed mol-ecular structure is compared to the results of DFT calculations.

Ruthenium arene complexes with triphenylphosphane ligands: cytotoxicity towards pancreatic cancer cells, interaction with model proteins, and effect of ethacrynic acid substitution

The anticancer behaviour of Ru arene complexes can be tuned by an appropriate choice of the site and linkage of the bioactive group to the phosphane ligand.

N,N-Bis(2-hy-droxy-eth-yl)di-thio-carbamato-κ2S,S']bis-(tri-phenyl-phosphane-κP)copper(I) chloro-form monosolvate: crystal structure, Hirshfeld surface analysis and solution NMR measurements.

The title compound, [Cu(C5H5NO2S2)(C18H15P)2]·CHCl3, features a tetra-hedrally coordinated CuI atom within a P2S2 donor set defined by two phosphane P atoms and by two S atoms derived from a symmetrically coordinating di-thio-carbamate ligand. Both intra- and inter-molecular hy-droxy-O-H⋯O(hydroxy) hydrogen bonding is observed: the former closes an eight-membered {⋯HOC2NC2O} ring, whereas the latter connects centrosymmetrically related mol-ecules into dimeric aggregates via eight-membered {⋯H-O⋯H-O}2 synthons. The complex mol-ecules are arranged to form channels along the c axis in which reside the chloro-form mol-ecules, being connected by Cl⋯π(arene) and short S⋯Cl [3.3488 (9) Å] inter-actions. The inter-molecular inter-actions have been investigated further by Hirshfeld surface analysis, which shows the conventional hydrogen bonding to be very localized with the main contributors to the surface, at nearly 60%, being H⋯H contacts. Solution NMR studies indicate that whilst the same basic mol-ecular structure is retained in solution, the tri-phenyl-phosphane ligands are highly labile, exchanging rapidly with free Ph3P at room temperature.

Cobaltoceniumethynyl gold(I) as an unusual heterodinuclear bioorganometallic fragment to study the biological properties of alkynyl gold complexes.

A cobaltoceniumethynyl gold(i) complex with a triphenylphosphane ligand triggered efficient cytotoxic effects in cancer cells in contrast to a derivative with two cobaltocenium moieties. The complex effectively inhibited the enzyme thioredoxin reductase (TrxR) suggesting this enzyme as a possible biological target. The cellular uptake of both metal fragments of the active complex was studied by atomic absorption spectroscopy and indicated a high biological stability of the complex.

Alkynyl gold(I) phosphane complexes: Evaluation of structure–activity-relationships for the phosphane ligands, effects on key signaling proteins and preliminary in-vivo studies with a nanoformulated complex

Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure–activity-relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2-furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4-ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion.

Crystal structure of [1-(3-ethoxy-2-oxidobenzylidene-κO2)-4-phenylthiosemicarbazidato-κ2N1,S](triphenylphosphane-κP)nickel(II)

In the title complex, [Ni(C16H15N3O2S)(C18H15P)], the NiII atom has a distorted tetra­hedral coordination geometry, comprised of N, S, O and P atoms of the tridentate thiosemicarbazide ligand and the P atom of the triphenylphosphane ligand. The benzene ring makes a dihedral angle of 53.08 (11)° with the phenyl ring of the phenyl­thio­semicarbazide moiety and dihedral angles of 73.69 (11), 20.38 (11) and 71.30 (11)° with the phenyl rings of tri­phenyl­phosphane ligand. A pair of N—H⋯N hydrogen bonds generates an R 2 2(8) ring graph-set motif. The eth­oxy group is disordered over two positions, with site occupancies of 0.631 (9) and 0.369 (9). The mol­ecular structure is stabilized by a weak intra­molecular C—H⋯O hydrogen bond. In the crystal, weak N—H⋯N and C—H⋯π inter­actions connect the mol­ecules, forming a three-dimensional network.

Crystal structures of di-iodido-bis-[(1S,5S)-4-mesityl-1,2,8,8-tetra-methyl-2,4-di-aza-bicyclo-[3.2.1]octan-3-yl-idene-κC (3)]palladium(IV) and di-chlorido-[(1S,5S)-4-mesityl-1,2,8,8-tetra-methyl-2,4-di-aza-bicyclo[3.2.1]octan-3-yl-idene-κC (3)](tri-phenyl-phosphane-κP)palladium(IV).

The mol-ecular structures of the chiral title compounds, [Pd(C19H28N2)2I2], (I), and [Pd(C19H28N2)Cl2(C18H15P)], (II), show a distorted square-planar coordination around the Pd(II) atoms with two halogenide (Hal) ligands each and two N-heterocyclic carbene (NHC) ligands in (I) or one NHC and one tri-phenyl-phosphane ligand in (II). The deviations of the Pd(II) atoms from the L 2Hal2 best plane (L = NHC or tri-phenyl-phosphane ligand) are 0.206 (1) Å for (I) and 0.052 (1) Å for (II). The crystal packings exhibit inter-molecular C-H⋯Hal hydrogen bonds.

The exopolyhedral ligand orientation (ELO) in 3-(nitrato-κO)-3,3-bis(triphenylphosphane-κP)-3-rhoda-1,2-dicarba-closo-dodecaborane(11) dichloromethane 2.2-solvate.

In the title compound, [Rh(C2H11B9)(NO3)(C18H15P)2]·2.2CH2Cl2, studied as a 2.2-solvate of what was assumed to be dichloromethane, the nitrate ligand lies cis with respect to both cage C atoms. Accordingly, the compound displays a pronounced preferred exopolyhedral ligand orientation (ELO) which is traced to both the greater trans influence of the cage B over the cage C atoms and the greater trans influence of the triphenylphosphane ligands over the nitrate ligand. The overall molecular architecture therefore agrees with that of a number of similar 3-L-3,3-L'2-3,1,2-closo-MC2B9H11 species in the literature.

Crystal structure of (benzene-carbo-thio-amide-κS)chloridobis-(tri-phenyl-phosphane-κP)silver(I).

In the mononuclear mixed-ligand title complex, [AgCl(C7H7NS)(C18H15P)2], the AgI ion is four coordinated by one S atom of a benzene­carbo­thio­amide ligand, two P atoms of two tri­phenyl­phosphane ligands and one chloride ion, displaying a distorted tetra­hedral coordination geometry. In the crystal, pairs of N—H⋯Cl hydrogen bonds form inversion dimers. An intra­molecular N—H⋯Cl hydrogen bond is also observed.

Synthesis of Ni(II) complexes with unsymmetric [O,N,O′]-pincer ligands and their use as precatalysts in carbon–carbon bond formations to access diarylmethanes

1-Acetyl-[1a,3,5-CF3,1-C(=O)CH3] and 1-benzoyl-5-hydroxypyrazolines [1b, 3,5-CF3, 1-C(=O)C6H5] have been synthesized and reacted with Ni(OAc)2·4H2O in the presence of PPh3 to form square planar nickel complexes, which revealed a O,N,O′-coordination. An additional coordination site on the nickel center is occupied by one triphenylphosphane ligand. After having investigated the properties of the complexes, catalytic experiments have been carried out to synthesize diarylmethanes. Applying the complexes in the nickel-catalyzed carbon–carbon cross coupling of aryl halides with benzylzinc bromide excellent yields and selectivities of the corresponding diarylmethane have been obtained. Moreover, various experiments have been performed to shed light on the underlying reaction mechanism.