Triphenylphosphine Co-ligands Research Articles

Pt(II) and Pd(II) complexes with coumarin-thiosemicarbazone hybrid ligands and triphenylphosphine coligand as potential anti T. cruzi agents

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. The disease is endemic in 21 Latin American countries, but it has also been found worldwide. Current treatments for Chagas disease are not effective in all stages of the disease and can have severe side effects. In recent years, there has been a growing interest in the development of new drugs for the treatment of Chagas disease, including metal complexes containing bioactive ligands. In this work, we designed and synthesized eight novel palladium and platinum complexes of the formula [M(L)(PPh3)] containing four different coumarin-thiosemicarbazone hybrid ligands (H2L) as bioactive ligands and triphenylphosphine as lipophilic co-ligand. Compounds were characterized in the solid state and in solution including the resolution of the crystal structure of two of them by single crystal X-ray diffraction. The activity of these hybrids and their corresponding complexes against T. cruzi, along with their unspecific cytotoxicity, was assessed. The results showed that the palladium complexes fairly improved the ligands’ anti-T. cruzi activity in vitro but also the cytotoxicity on some mammalian cell lines. The most active palladium compound decreased the rate of parasitic infection of Vero cells. Synergy studies with benznidazole were also performed for this compound. In addition, we explored mitochondrion disruption and ROS generation as potential modes of action for the obtained compounds. Further studies are needed to optimize the design of new compounds to attain less unspecific toxicity and higher anti T. cruzi activity.

New Copper Complexes with N,O-Donor Ligands Based on Pyrazole Moieties Supported by 3-Substituted Acetylacetone Scaffolds

The new 3-monosubstituted acetylacetone ligands, 3-(phenyl(1H-pyrazol-1-yl)methyl)pentane-2,4-dione (HLacPz) and 3-((3,5-dimethyl-1H-pyrazol-1-yl)(phenyl)methyl)pentane-2,4-dione (HLacPzMe), were synthesized and used as supporting ligands for new copper(II) and copper(I) phosphane complexes of the general formulae [Cu(HLacX)2(LacX)2] and [Cu(PPh3)2(HLacX)]PF6 (X = Pz (pyrazole) or PzMe (3,5-dimethylpyrazole)), respectively. In the syntheses of the Cu(I) complexes, the triphenylphosphine coligand (PPh3) was used to stabilize copper in the +1 oxidation state, avoiding oxidation to Cu(II). All compounds were characterized by CHN analysis, 1H-NMR, 13C-NMR, FT-IR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). The ligands HLacPz (1) and HLacPzMe (2) and the copper complex [Cu(PPh3)2(HLacPz)]PF6 (3) were also characterized by X-ray crystallography. The reactivity of these new compounds was investigated and the new compounds 4-phenyl-4-(1H-pyrazol-1-yl)butan-2-one (7) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-4-phenylbutan-2-one (8) were obtained in basic conditions via the retro-Claisen reaction of related 3-monosubstituted acetylacetone, providing efficient access to synthetically useful ketone compounds. Compound 8 was also characterized by X-ray crystallography.

DNA/BSA binding studies and in vitro anticancer and antibacterial studies of isoelectronic Cu(I)- and Ag(I)-pyridinyl Schiff base complexes incorporating triphenylphosphine as co-ligands

Four mononuclear Ag(I) and Cu(I) Schiff base complexes of the type [M(L)(PPh3)2]X [where M = Ag+ or Cu+, L = (E)-N-(2-fluorophenyl)-1-(pyridin-2-yl)methanimine (fpm) or (E)-1-(pyridin-2-yl)-N-(p-tolyl)methanimine (ptm) and X = NO3–] have been synthesized and characterized by various spectroscopic and analytical techniques. The analysis shows that the complexes are four-coordinates formed via the nitrogen atoms of a bidentate fpm or ptm ligands and two phosphorus atoms from the triphenylphosphine co-ligands. Two of the complexes were structurally characterized by single crystal X-ray diffraction revealing a distorted trigonal pyramidal geometry around the Ag(I) or Cu(I) center. The binding affinity of the complexes with calf thymus-DNA (CT-DNA) and bovine serum albumin (BSA) was determined using UV–visible spectroscopy. The interaction of the complexes with CT-DNA revealed the strong stacking interaction between the aromatic chromophore of the complexes and the base pairs of the CT-DNA. The study of the complexes with BSA showed moderate affinity to BSA, suggesting that complexes 1–4 can be delivered and dispositioned in vivo. Invitro anticancer activity of the synthesized complexes was evaluated against non-cancerous human embryonic kidney 293 (HEK293), cervical cancer cell (HELA), breast cancer cell (MDA-MB231) and malignant human melanoma cell (A375). High antiproliferative effects of the complexes on HELA (with EC50 values between 1.82±1.23 and 10.66±2.87 μM better than cisplatin with EC50 > 50 μM) and MDA-MB231(≈2 to 7-fold effective than cisplatin) were recorded. Further, the invitro antibacterial activity of the synthesized compounds was evaluated against S. aureus, E. coli, S. typhi and P. aeruginosa using the disc diffusion method from which the Cu(I) complexes showed better inhibitory effects than the Ag(I) complexes.

Neutral, Heteroleptic [Cu(I)(PPh3 )2 (4H-imidazolato)] Complexes: Ligand Exchange Reactivity, Redox Properties, Excited-State Dynamics.

Cu(I) 4H-imidazolate complexes are rare examples of Cu(I) complexes with chelating anionic ligands and are potent photosensitizers with unique absorption and photoredox properties. In this contribution, five novel heteroleptic Cu(I) complexes with monodentate triphenylphosphine co-ligands are investigated. As a consequence of the anionic 4H-imidazolate ligand and in contrast to comparable complexes with neutral ligands, these complexes are more stable than their homoleptic bis(4H-imidazolato)Cu(I) congeners. Here, the ligand exchange reactivity was studied by 31 P-,19 F-, and variable temperature NMR and the ground state structural and electronic properties by X-ray diffraction, absorption spectroscopy, and cyclic voltammetry. The excited-state dynamics were investigated by femto- and nanosecond transient absorption spectroscopy. The observed differences, with respect to chelating bisphosphine bearing congeners, are often due to the increased geometric flexibility of the triphenylphosphines. These observations render the investigated complexes interesting candidates for photo(redox)reactions not accessible with chelating bisphosphine ligands.

Synthesis, characterization, crystal structure, and theoretical studies of a mixed-ligand copper(I) iodide complex of an asymmetric Schiff base ligand 2-((pyridin-4-yl)methelenamino)-3-aminomaleonitrile and triphenylphosphine co-ligand

Single pot synthesis of a new mixed-ligand iodide bridged dimeric Cu(I) complex, [L2CuI2(μ-I)2(PPh3)2](1) has been carried out by combining copper(I)iodide, an asymmetric Schiff base ligand 2-((pyridin-4-yl)methelenamino)-3-aminomaleonitrile (L) and a co-ligand triphenylphosphine (PPh3). L and 1 have been characterized by 1H NMR, IR and EIMS spectrometry, elemental analysis and DFT studies. The crystal structure of 1 has been determined by single-crystal X-ray analysis and it has been found that it is a dimer with —{CuI—(m-I2)—CuI}— rhomboid core with the bridged iodide ion. 1 crystallized as 1·CH2Cl2. At room temperature in dichloromethane the ligand L is non-emissive whereas the complex 1 is photoluminescent. The E1/2 value of the CuI—CuII couple of 1 in dichloromethane is 0.46 V (vs. Ag/AgCl in 1 M KCl, scan rate 100 mV/s). The Hirshfeld surface analysis of the complex 1·CH2Cl2 showed H⋯H, N⋯H and I⋯H interactions of 52.3 %, 13.1 % and 7.4 %, respectively, which revealed that the main intermolecular interactions were H⋯H intermolecular interactions.

Synthesis, crystal structure, and thermal behavior of a diiron toluenethiolate complex with triphenylphosphine coligand

A bis(p-toluenethiolato) dinuclear-carbonyl complex with triphenylphosphine coligand, [μ-(SC6H4CH3-p)2Fe2(CO)5(PPh3)], has been synthesized from [μ-(SC6H4CH3-p))2Fe2(CO)6] via facile CO substitution by PPh3 in 33% yield. The structure of [μ-(SC6H4CH3-p)2Fe2(CO)5(PPh3)] has been determined by X-ray crystallography and spectroscopic measurements. In the solid state, the compound adopts a butterfly conformation with anti-orientation of the p-tolyl groups and apical position of triphenylphosphine. Thermogravimetric studies reveal that [μ-(SC6H4CH3-p)2Fe2(CO)5(PPh3)] undergoes sequential decomposition eliminating all of the CO ligands at ca 197 °C, followed by cleavage of the tolyl and PPh3 groups below ca 258 °C.

Inhibition of DNase I Enzyme with Nickel(II) Triphenylphosphine Complexes Incorporating Tridentate Schiff Base Ligands in Vitro

The nickel(II) complexes containing 3-methoxy-salicylaldehyde-N4-R thiosemicarbazones (R:-H2,-propyl)with triphenylphosphine coligands have been synthesized. The structure of Ni(II)-centered metal complex was approved by elemental analysis and melting point. The solid-state structure of complex 2 bearing PPh3 as co-ligand was clarified by single crystal X-ray crystallography, which revealed square planar geometry around Ni(II) ion. Thiosemicarbazone ligands are coordinated by ONS mode to nickel(II). The potential of these complexes to inhibit the DNase I enzyme, which uses DNA as a substrate, was investigated in vitro. The results revealed that the compounds inhibited the DNase enzyme in directly and/or indirectly (by masking of DNA molecules) at ≥0.1 µg/ml concentrations in vitro.

X-ray diffraction, spectroscopic and DFT studies on nickel(II)-triphenylphosphine complexes of 2-hydroxyacetophenone thiosemicarbazones

This work presents a combined experimental and theoretical study on new synthesized ONN and ONS chelating 2-hydroxyacetophenone thiosemicarbazone ligands and their nickel(II) complexes with triphenylphosphine co-ligand. The 5-bromo-2-hydroxyacetophenone thiosemicarbazone ligand (L1) coordinates to nickel through the phenolic-O, azomethine-N and thiole-S atoms and the complex [Ni(L1)(PPh3)] (1) is formed an ONSP donor set with P atom of triphenylphosphine ligand. The 5-bromo-2-hydroxyacetophenone-S-methyl-thiosemicarbazone ligand (L2) is functional a thioamide nitrogen instead of a sulfur atom, so complex [Ni(L2)(PPh3)] (2) have ONNP donor set. The spectroscopic properties of all compounds have been determined by IR, 1H NMR and UV–Vis spectroscopy techniques and the crystal structure of L1, 1 and 2 have also been studied using X-ray diffraction. The molecular geometries obtained by X-ray analyzes in the ground state were compared with the optimized geometries which were calculated using the DFT/B3LYP method. The 6-311G(d,p) basis set for C, H, N, O, P, S atoms and LANL2DZ basis set for Ni atom were chosen in all theoretical calculations. In addition to molecular geometries, the vibrational frequencies, electronic transitions and 1H NMR chemical shifts of the compounds were computed and compared with the experimental values. The electronic absorption spectra of the both complexes were predicted by using the time-dependent DFT method. The HOMO–LUMO analyses were carried out and the chemical reactivity parameters (chemical hardness and softness, electronegativity, chemical potential and electrophilicity index) were calculated for studied compounds.

Synthesis and reactivity of osmium and ruthenium PBP–LXL boryl pincer complexes

The reaction of HB(NCH2PPh2)2C6H4-1,2 with [OsCl(Ph)(CO)(PPh3)2] affords the boryl pincer complex [OsCl(CO)(PPh3){B(NCH2PPh2)2C6H4}]. This complex, and its ruthenium analogue were observed to undergo various reactions involving substitution of the chloride and triphenylphosphine co-ligands to give new complexes [MCl(CO)(CNC6H2Me3){B(NCH2PPh2)2C6H4}] (M=Ru, Os), [MH(CO)(PPh3){B(NCH2PPh2)2C6H4}] (M=Ru, Os) and [Ru(κ2-S,S′-S2CNEt2)(CO){B(NCH2PPh2)2C6H4}]. The ruthenium complex [RuH(CO)(PPh3){B(NCH2PPh2)2C6H4}] was found to react with carbon disulfide and carbon monoxide to give the complexes [Ru(κ2-S,S′-S2CH)(CO){B(NCH2PPh2)2C6H4}] and [RuH(CO)2{B(NCH2PPh2)2C6H4}], respectively, the latter as an apparently interconverting mixture of cis and trans dicarbonyl isomers.

First 3,5-diacetyl-1,2,4-triazol derived mono(thiosemicarbazone) and its palladium and platinum complexes: Synthesis, structure and biological properties

Preparation and characterization of 3,5-diacetyl-1,2,4-triazol mono(4-phenylthiosemicarbazone) ligand, H3L, and its derived palladium(II) and platinum(II) complexes, [Pd(HL)(PPh3)] and [Pt(HL)(PPh3)], is described. The molecular structures of the two new metal complexes have been determined by single crystal X-ray diffraction. In both complexes the metal ion is four-coordinated with a [N2SP] donor environment, via one triazole nitrogen atom, the azomethine nitrogen and thione sulfur atoms of the thiosemicarbazone moiety and a phosphorous atom from the triphenylphosphine coligand. The cytotoxicity of the new compounds synthesized was investigated in vitro against T-47D, A2780 and A2780cisR human cancer cell lines, being H3L the species with the highest activity. In addition, the DNA binding ability of H3L with calf thymus DNA was explored by UV–Vis absorption spectroscopy.

Synthesis and characterization of a new bioactive mono(thiosemicarbazone) ligand based on 3,5-diacetyl-1,2,4-triazol diketone and its palladium and platinum complexes

Preparation and characterization of a new 4N-p-chlorophenyl substituted thiosemicarbazone ligand, H3L2, and its derived palladium(II) and platinum(II) complexes, [Pt(HL2)(PPh3)] and [Pd(HL2)(PPh3)], is described. The molecular structures of the two new metal complexes have been determined by single crystal X-ray diffraction. In both complexes the metal ion is four-coordinated with a [N2SP] donor environment, via one triazole nitrogen atom, the azomethine nitrogen and thione sulfur atoms of the thiosemicarbazone moiety and a phosphorous atom from the triphenylphosphine coligand. The biological activity of the new compounds synthesized was initially explored by determining their antiproliferative activity in vitro against T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H3L2 since is capable not only to circumvent cisplatin resistance in A2780cisR cells but also to exhibit high antiproliferative activity in breast cancer T-47D cells.

Mixed ligand palladium(ii) complexes of 6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4N-substituted thiosemicarbazones with triphenylphosphine co-ligand: Synthesis, crystal structure and biological properties

A series of new 6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4N-substituted thiosemicarbazone ligands (H2L1–H2L5) and their corresponding palladium(II) complexes [Pd(L1)(PPh3)] (1), [Pd(L2)(PPh3)] (2), [Pd(HL3)(PPh3)]Cl (3), [Pd(L4)(PPh3)] (4) and [Pd(L5)(PPh3)] (5), have been synthesized in order to evaluate the effect of terminal N-substitution in thiosemicarbazone moiety on coordination behaviour and biological activity. The new ligands and their corresponding complexes were characterized by analytical and various spectral techniques. The molecular structure of the complexes 2–5 were characterized by single crystal X-ray diffraction studies which revealed that the ligands H2L2, H2L4 and H2L5 are coordinated to palladium(II) as binegative tridentate (ONS2−) by forming six and five member rings whereas, the ligand H2L3 coordinated to Pd(II) as uninegative tridentate (ONS−). The interactions of the new complexes with calf thymus DNA (CT-DNA) have been evaluated by absorption and ethidium bromide (EB) competitive studies which revealed that complexes 1–5 could interact with CT-DNA through intercalation. Further, the interactions of the complexes with bovine serum albumin (BSA) were also investigated using UV-visible, fluorescence and synchronous fluorescence spectroscopic methods, which showed that the new complexes could bind strongly with BSA. Antioxidant studies showed that all the complexes have a strong antioxidant activity against 2-2′-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2′-azino-3-ethylbenzthiazoline-6-sulfonic acid diammonium salt (ABTS) cation radical. In addition, in vitro cytotoxicity of the complexes against human lung cancer (A549) cell line was assayed which showed that 4 has higher cytotoxic activity than the rest of the complexes and cisplatin.

Nickel(II) complexes of ONS and ONN chelating thiosemicarbazones with triphenylphosphine co-ligands

Reactions of 5-bromo-2-hydroxy-benzaldehyde-S-R-4-R1-thiosemicarbazones, [R, R1 = H,H (L1); CH3, H (L2); H, C6H5 (L3); CH3, C6H5 (L4)] with [Ni(PPh3)2Cl2] in 1:1 molar ratio yielded complexes of general formula [Ni(L)(PPh3)]. While the complexes of L1 and L3 involve the ONS donor set of the thiosemicarbazone, the L2 complexes utilize the ONN set. The reaction of L4 and the nickel salt gave the L3 complex by loss of the CH3 group from the sulphur. The complexes were characterized by physico-chemical and spectroscopic methods. The structures of the L1 and L2 complexes have been determined by single crystal X-ray diffraction and a new coordination mode (ONN) of salicylaldehyde thiosemicarbazones has been identified.

Technetium Complexes of a Hydrazinonicotinamide-Conjugated Cyclic Peptide and 2-Hydrazinopyridine: Synthesis and Characterization.

Ternary ligand technetium complexes of a hydrazinonicotinamide-conjugated cyclic peptide (HYNICtide: cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-(6-hydrazinonicotinamido)hexanamide)))) and 2-hydrazinopyridine (HYPY) were prepared and characterized by various spectroscopic methods. The HPLC concordance experiments for (99m)Tc and (99)Tc analogues show clearly that the same complexes are prepared on the no-carrier-added ((99m)Tc) and the carrier-added ((99)Tc) levels. Using a chirality experiment, it was demonstrated that the presence of two radiometric peaks in the HPLC chromatograms of RP444, RP445, and RP446 is due to the resolution of diastereomers, which result from the presence of chiral cyclic peptide and the formation of two enantiomers of the technetium chelate. In a ligand challenge experiment, we found that the high solution stability of these ternary ligand [(99m)Tc]HYNICtide complexes is due to their kinetic inertness. The 1:1:1:1 composition for Tc:HYNICtide:L:tricine (L = TPPTS, TPPDS, and TPPMS) in these ternary ligand [(99)Tc]HYNICtide complexes is confirmed by (1)H NMR and FAB mass spectral data and is completely consistent with that determined on the tracer ((99m)Tc) level. In addition, the IC(50) values of RP444, RP445, and RP446 and the two isomeric forms of RP444 were determined using a platelet IIb/IIIa binding assay. Both isomeric forms of RP444 were found to have the same binding affinity (IC(50) = 13 +/- 2 nM). Complexes [(99)Tc(HYPY)(PPh(3))(2)Cl(2)] and [(99)Tc(HYPY)(PPh(3))(tricine)] were isolated from the reaction of HYPY with [n-Bu(4)N][TcOCl(4)(-)] in the presence of excess tricine and triphenylphosphine. [(99)Tc(HYPY)(PPh(3))(tricine)] serves as a model for ternary ligand [(99m)Tc]HYNICtide complexes. Both complexes have been characterized by HPLC, spectroscopic (IR, NMR, and FAB-MS) methods, and elemental analysis. The HPLC concordance for complexes [(99m)Tc(HYPY)(PPh(3))(tricine)] and [(99)Tc(HYPY)(PPh(3))(tricine)] shows that the two complexes are identical. The NMR ((1)H and (13)C) data suggests that the complex [(99)Tc(HYPY)(PPh(3))(tricine)] have an octahedral coordination geometry with a monodentate diazenido HYPY, a tetradentate tricine, and a monodentate triphenylphosphine coligand.