Mixed-ligand Palladium Research Articles

Mixed ligand palladium(II) complexes of N-hydroxy-methylsaccharin (Sac-CH2OH): synthesis, characterization and biological studies

Reaction of Na2PdCl4 with two equivalents of N-hydroxymethylsaccharin (Sac-CH2OH) in the presence of NEt3 afforded trans-[Pd(κ2-Sac-CH2O)2]. Further reaction of [Pd(κ2-Sac-CH2O)2] with one equivalent of diphosphine (L2), Ph2P(CH2) n PPh2, (n = 1, dppm; 2, dppe and 3, dppp), Ph2P(S)(CH2)P(S)Ph2 (dppmS2) or Ph2P(O)(CH2)2P(O)Ph2 (dppeO2) afforded mixed ligand complexes [Pd(κ1-Sac-CH2O)2(L2)], while reaction with two equivalents of Ph3P, Ph3PO or Ph3PS (L) gave trans-[Pd(κ1-Sac-CH2O)2(L)2]. The N-hydroxymethylsaccharinate anion acts as a monodentate ligand, coordinating to the palladium center through the hydroxymethyl oxygen atom. The complexes were characterized by physico-chemical and spectroscopic methods. In addition, the free ligand N-hydroxymethylsaccharin and some of the complexes were screened in vitro for antibacterial activity.

New formamidine ligands and their mixed ligand palladium(II) oxalate complexes: Synthesis, characterization, DFT calculations and in vitro cytotoxicity

A series of new ternary palladium(II) complexes of the type [Pd(L1–4)ox]·xH2O where L=formamidine ligands and ox=oxalate, were synthesized and characterized by elemental analyses, magnetic susceptibility, UV–Vis, infrared (IR) and mass spectroscopy and thermal analysis. The spectroscopic data indicated that the formamidine ligands act as bidentate N2 donors and the oxalate as O2 ligand. The complexes (1–4) are diamagnetic and the optimization of their structures indicated that the geometry is distorted square planer with O–Pd–O and N–Pd–N bond angles ranged 82.70–83.87° and 88.21–95.02°; respectively which is acceptable for the heteroleptic complexes. The dipole moment of the complexes (13.97–18.77Debye) indicating that the complexes are more polarized than the ligands (1.93–4.96Debye). The complexes are thermally stable as shown from their relatively higher overall activation energies (441–688kJmol−1). The ligands and the complexes are proved to have good cytotoxicity with IC50 (μM) in the range of (0.011–0.168) against MCF-7, (0.012–0.150) against HCT-116, (0.042–0.094) against PC-3 and (0.006–0.222) against HepG-2 cell lines, which open the field for further application as antitumor compounds.

New mixed ligand palladium(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands: Synthesis, structural characterization, binding interactions with DNA and BSA, in vitro cytotoxicity studies and DFT calculations

The complexes [Pd(valp)2(imidazole)2] (1), [Pd(valp)2(pyrazine)2] (2) (valp is sodium valproate) have been synthesized and characterized using IR, 1H NMR, 13C{1H} NMR and UV–Vis spectrometry. The interaction of complexes with CT-DNA has been investigated using spectroscopic tools and viscosity measurement. In each case, the association constant (Kb) was deduced from the absorption spectral study and the number of binding sites (n) and the binding constant (K) were calculated from relevant fluorescence quenching data. As a result, a non-covalent interaction between the metal complex and DNA was suggested, which could be assigned to an intercalative binding. In addition, the interaction of 1 and 2 was ventured with bovine serum albumin (BSA) with the help of absorption and fluorescence spectroscopy measurements. Through these techniques, the apparent association constant (Kapp) and the binding constant (K) could be calculated for each complex. Evaluation of cytotoxic activity of the complexes against four different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate. Moreover, density functional theory (DFT) calculations were employed to provide more evidence about the observed data. The majority of trans isomers were supported not only by energies, but also by the similarity of its calculated IR frequencies, UV adsorptions and NMR chemical shifts to the experimental values.

Mono-nuclear cis-Pd(II) chloride complex of the thio-nucleotide analogue 5-methyl-thiouracil and its biological activity

The new mixed ligand palladium(II) complex of formula cis-Cl-[PdCl2(TPP)(MTUC)]·3(H2O) (1) was obtained by reacting 6-methyl-thiouracil (MTUC) with triphenylphosphine (TPP). The complex was characterized by vibrational spectroscopy (FT-IR), 1H NMR, UV–Vis spectroscopic techniques and its structure was confirmed by X-ray crystallography. Mixed ligand complexes of palladium(II) dichloride with thiones and phosphines are very rare in the literature. Compound 1 is the fourth of this kind of compounds which has also been examined for its biological effects.Complex 1 was evaluated for its in vitro cytotoxic activity (cell viability) against human cancer cell lines: MCF-7 (breast) and HeLa (cervical) with tryban blue assay. The results showed that 1 mediates a mild cytotoxic response to the tested cancer cell lines. The binding affinity of 1 towards the intracellular molecules DNA and lipoxygenase (LOX) was studied for the evaluation of the mechanism of its cytotoxicity. Partial least squares (PLS) regression analysis was carried out to correlate the variation of the IC50 values (Y-variables) with the variations of energetic parameters (X-variables), calculated from molecular docking calculation for 1 and related palladium(II) complexes reported.

Spectroscopic Characterization,In VitroCytotoxicity, and Antioxidant Activity of Mixed Ligand Palladium(II) Chloride Complexes Bearing Nucleobases

Mixed-ligand palladium(II) chloride complexes bearing the nucleobases, adenine (Ad), cytosine (Cyt), and guanine (Gua), have been synthesized and characterized by UV-vis spectrophotometric methods, magnetic susceptibility, molar conductivity, elemental analysis, FTIR, and1H-NMR. The complexes were found to have the composition cis-[PdCl2(Gua)(Cyt)], cis-[PdCl2(Ad)(Cyt)], and cis-[PdCl2(Ad)(Gua)]. A four-coordinated square-planar geometry is proposed for these Pd(II) complexes based on magnetic evidence and electronic spectra. The complexes as well as the free nucleobase ligands were tested for theirin vitrocytotoxicity on human promyelocytic leukemia (HL60) and human histiocytic leukemia (U937) cell lines. cis-[PdCl2(Ad)(Gua)] showed IC50values of 11.29 ± 2.91 and 8.31 ± 1.44 μM against HL60 and U937, respectively, which was higher than that of the positive control (curcumin) against U937. The complexes also showed significant antioxidant activity when tested against 2,2-diphenyl-1-picrylhydrazylradical (DPPH).

CS Coupling Using a Mixed‐Ligand Pd Catalyst: A Highly Effective Strategy for Synthesizing Arylthio‐Substituted Heterocycles

CS coupling: A variety of arylthio-substituted heterocycles can be prepared through CS coupling of the corresponding halide-substituted heterocycles by using a mixed-ligand palladium catalyst, [Pd2(dba)3]/ Xantphos/CyPF-tBu (see scheme; dba=dibenzylideneacetone). This catalytic system is extremely powerful and efficient, allowing even CCl bond activation.

New dimeric and supramolecular mixed ligand Palladium(II) dithiocarbamates as potent DNA binders

Five Pd(II)-based potential potent metallopharmaceuticals (1–5) of the general formula [(DT)Pd(PR3)Cl], where DT=dibutyldithiocarbamate (1,2), dipropyldithiocarbamate (3), bis(2-methoxyethyl)-dithiocarbamate (4), dimethyldithiocarbamate (5); PR3=triphenylphosphine (1), diphenyl-p-tolylphosphine (2), diphenyl-t-butylphosphine (3), diphenyl-2-methoxyphenylphosphine (4), p-cholorodiphenylphosphine (5), have been synthesized and characterized using FT-IR, Raman, and multinuclear-NMR spectroscopy. The X-ray single crystal analysis (1 and 2) reveals the Pd(II) moiety is in a distorted square–planar arrangement with two positions being occupied by the bidentate dithiocarbamate ligand, while the other two positions are occupied by a phosphine ligand and a chloro group. The packing diagrams confirmed that the intermolecular Cl⋯H interactions are not only the main cause of deviation from an ideal square planar geometry, but are also responsible for the Pd–S bond lengths variation. The DNA binding ability of the complexes was examined by cyclic voltammetry (CV). The cyclic voltammograms of the synthesized metallopharmaceuticals followed irreversible electrochemical behavior, which indicate the high reactivity of the reduced form of complexes. The results obtained from CV evidenced the catalytic role of DNA in enhancing the electron transfer processes of the complexes. The DNA binding studies are expected to provide useful insights about the unexplored mechanism by which anticancer drugs exert their biochemical action.

Synthesis, characterization, and biological activity of five new mixed-ligand palladium(II) complexes with ethylenediamine and 4-toluenesulfonyl-L-amino acid dianion

Five new palladium(II) complexes with 4-toluenesulfonyl-L-amino acid dianion and en, [Pd(en)(TsserNO)] (1), [Pd(en)(TsglyNO)] (2), [Pd(en)(TsalaNO)] · 1.5H2O (3), [Pd(en)(TsleuNO)] · H2O (4), and [Pd(en)(TspheNO)] · 2H2O (5), have been synthesized and characterized by elemental analysis, IR, UV, 1H NMR, and mass spectrometry. Crystal structure of 1 has been determined by X-ray diffraction analysis. The cytotoxicity was tested by MTT and SRB assays. The results indicate 1–5 exert cytotoxic effects against HL-60, Bel-7402, BGC-823, and KB cell lines and 5 displays the best cytotoxicity. The structure–activity relationships suggest that both amino acid and N-containing ligands have important effects on cytotoxicity.

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.

Novel mixed-ligand palladium complexes [Pd 2(acac) 3NO 3] and [Pd(acac)NO 3] n involving O,O- and γ-C-bonded acetylacetonate linkers

The reaction of the palladium nitrate trans-[Pd(NO 3) 2(H 2O) 2] with acetylacetone affords mononuclear [Pd(acac) 2] (acac = acetylacetonate), mixed-ligand binuclear [Pd 2(acac) 3NO 3] ( 1) and polynuclear [Pd(acac)NO 3] n ( 2) complexes depending on the Pd:acetylacetone ratio in the reaction mixture. The binuclear 1 and insoluble polynuclear 2 were isolated and studied by single-crystal X-ray diffraction ( 1) and solid-state 13C MAS NMR ( 1 and 2). It was found that in both compounds the Pd ions are linked together through bridging acetylacetonate ligands where one metal atom is connected to the usual O,O-donor sites, whereas the other metal atom forms a bond with the γ-carbon center. Based on a topological quantum-chemical method, the Pd –γ-C bond was classified as a strained dative bond.

Mixed Ligand Palladium(II) Complex with NS‐Bidentate S‐Allyldithiocarbazate Schiff Base: Synthesis, Spectral Characterization, Crystal Structure and Decoding Intermolecular Interactions with Hirshfeld Surface Analysis

AbstractA new mixed ligand palladium(II) complex with bidentate NS‐donor chelate, [PdCl(PPh3)L] (L: S‐allyl β‐N‐(benzylidene)dithiocarbazate), has been prepared and characterized using single crystal X‐ray diffraction and spectroscopic (electronic, IR, 1H NMR and 13C NMR) techniques. The shorter PdP bond distance, 2.255(7) Å, than the sum of the single bond radii for palladium and phosphorus (2.41 Å), showed partial double bond character. Visualizing and exploring the crystal structure using Hirshfeld surface analysis showed the presence of π··· π, N··· π, CH··· π, Cl···H and weak CH···S interactions as most important intermolecular interactions in the crystal lattice, which are responsible to extension of the supramolecular network of the compound and stabilization of the crystal structure.

Synthesis and Reactivity of Mixed-Ligand Palladium(II) Organometallic Complexes with Phosphites and Bis(pyrazol-1-yl)methane

New cationic organometallic palladium(II) complexes of general formula [PdMe(NN)P(OR)3]ClO4{NN = bis(pyrazol-1-yl)methane (BPM) and bis(3,5-dimethylpyrazol-1-yl)methane (Me2BPM); P(OR)3 = phosphites} have been synthesized and characterized. The isolation of the intermediate reaction products has highlighted the formation mechanism of these species. By reacting [PdMe(BPM)P(OEt)3]ClO4 with the Cl− and SeCN− ions the neutral species PdClMe(BPM)P(OEt)3 and PdMe(SeCN)(BPM)P(OEt)3 have been prepared, the last one as a mixture of isomers. The NMR data suggest that these neutral complexes are stabilized by an anagostic interaction between a hydrogen atom of the BPM methylene bridge and the palladium center. The reaction of [PdMe(BPM)P(OEt)3]ClO4 with CO and tosylmethyl isocyanide allowed the isolation of the corresponding insertion products. Preliminary studies showed that the cationic acyl complex [Pd(COMe)(BPM)P(OEt)3]ClO4 is an active catalyst toward styrene polymerization in the presence of CO.

Effect of Br− on the Adsorption Rate of Palladium(II) Ions onto Condensed-Tannin Gel in Chloride Media

In chloride media, chloropalladium(II) species are adsorbed onto tannin gel particles through an inner-sphere redox reaction mechanism containing the intermediate step, formation of a ligand-substituted Pd(II)-tannin complex. In this Pd(II) adsorption process, it was observed that the adsorption rate can be increased by introducing Br−, a softer ligand than Cl−, into the aqueous chloride solution. The formation of mixed-ligand palladium(II) complexes accelerates the rate of ligand-substitution reactions with the hydroxyl groups of tannin gel by the trans effect. The adsorption condition can be optimized by controlling the [Brtot]/[Cltot] ratio, in which the predominant Pd(II) species are bromo-chloro palladium(II) complexes, the favorable species for the trans effect.

Synthesis, Spectroscopic, and Anticancerous Properties of Mixed Ligand Palladium(II) and Silver(I) Complexes with 4,6-Diamino-5-hydroxy-2-mercaptopyrimidine and 2,2'-Bipyridyl.

Synthesis of two new water-soluble mixed ligand [Pd(bpy)(dahmp)]Cl and [Ag(bpy)(Hdahmp)]NO3 complexes (dahmp and Hdahmp are the deprotonated monoanion and the protonated neutral 4,6-diamino-5-hydroxy-2-mercaptopyrimidine, resp.) is reported. The composition of the reported complexes was discussed on the bases of IR, 1H NMR, and mass spectra, as well as conductivity and thermal measurements. The reported complexes display a significant anticancer activity against Ehrlich ascites tumor cells (EACs). The higher activity of these complexes with their higher conductivity values corresponds to their complete ionization in aqueous solution.

Mixed-ligand palladium(II) complexes with amino acids, cytosine, and adenine

pH titration shows that 1 : 1 : 1 mixed-ligand complexes are formed in the systems palladium(II)-Cyt-Glu-H2O (loggB = 19.73) and palladium(II)-Cyt-Lys-H2O (logβ = 16.20). Complexes Pd(C5H5N5)(C5H8NO4)Cl, Pd(C5H5N5)(C6H13N2O2)Cl, Pd(C4H5N3O)(C6H13N2O2)Cl, and Pd(C4H5N3O)(C5H8NO4)Cl are synthesized and characterized by chemical analysis, X-ray powder diffraction, and thermogravimetry. The coordination mode of amino acids, cytosine, and adenine to the palladium(II) ion is determined.

Mixed-ligand platinum and palladium complexes based on dinitrogen chelating ligands and a pyridine bearing the nitronylnitroxide radical

Novel cationic mixed-ligand palladium and platinum complexes based on the chelating ligands 4,7-dimethyl-1,10-phenanthroline and 2,2′-bipyridine with a pyridine bearing the nitronylnitroxide radical are reported. The synthesis, X-ray crystal structures and magnetic properties of the two complexes [Pd(4,7-dimethyl-1,10-phenanthroline)(NIT-pPy) 2](PF 6) 2. DMF and [Pt(2,2′-bipyridine- N,N′)(NIT-pPy) 2](PF 6) 2 · 0.25H 2O, (where NIT-pPy = 2-(p-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) are described. The two metal complexes show a strained square planar geometry. Short intermolecular contacts take place through the nitroxide groups and weak intermolecular antiferromagnetic interactions are dominant at low temperature.

Synthesis, Characterization of Mixed Ligand Palladium(II) Complexes of Triphenylphosphine and Anilines and their Enzyme Inhibition Studies against β-glucuronidase. The Crystal Structure of trans-dichloro-(m-chloroaniline)(triphenylphosphine)palladium(II)

A number of palladium(II) complexes with Ph3P and aromatic amines as ligands having the general formula [(Ph3P)Pd(Ph3P)(NH2R)Cl2] {where R = Ph (1), m-ClC6H4 (2), p-ClC6H5 (3)} and [Pd(CH3NHPh)Cl2] (4), have been synthesized and characterized by elemental analysis, IR, 1H and 13C NMR. The X-ray crystal structure of [(Ph3P)Pd(m-ClC6H4NH2)Cl2] · CH2 Cl2 (2) shows a distorted square planar environment around the Pd(II) ion with the P–Pd–N and Cl(1)–Pd–Cl(2) bond angles of 174.88(5)° and 176.77(2)° respectively. The complexes were screened for enzyme inhibition activity against β-glucuronidase and found to be active.

Mixed ligand palladium(II) complexes of oxalate and malonate with vitamin-B6 molecules: synthesis, crystal structure and kinetics

The synthesis of six mononuclear palladium complexes of general formula [Pd(ox)/(mal)L2] and [Pd(ox)/(mal)L′] (ox = oxalate, mal = malonate, both L and L′ are vitamin-B6 molecules (I), L = pyridoxine, pyridoxal and L′ = pyridoxamine) has been achieved. The structures of these compounds were established by elemental analysis, i.r. and 13C-n.m.r. [Pd(oxalate)(pyridoxine)2] was analyzed by single crystal X-ray diffraction. It exhibits square planar coordination with bond lengths 2.015 (2) A for Pd—N and 2.010 (2) A for Pd—O. The interaction of [Pd(ox)2]2− and [Pd(mal)2]2− with L has been followed kinetically in order to look into the nature of products and the mechanism of formation under the conditions [PdII-chelate] ≫ [L] and [L′].

Synthesis, characterization, solution equilibria and DNA binding of some mixed-ligand palladium(II) complexes. Thermodynamic models for carboplatin drug and analogous compounds

A series of ternary complexes of palladium(II) with ethylenediamine (en) and dicarboxylate ligands of the type [Pd(en)L], where L=malonato ( I), methylmalonato ( II), dimethylmalonato ( III) and 1,1-cyclobutanedicarboxylato ( IV), were synthesized and characterized by elemental analysis, IR spectroscopy and TG-DTA thermal analysis. The X-ray crystal structures for the compounds II and IV are described. The stability of these dicarboxylato complexes in aqueous solution has been investigated by potentiometric measurements. The formation constants calculated for these dicarboxylato complexes and those reported in the literature for the corresponding hydroxo- and chloro- complexes of the Pd(en) moiety have been used to obtain species distribution diagrams. In addition, the interaction of the dicarboxylato complexes and the dichloro complex [Pd(en)Cl 2] ( V) with DNA was studied by various methods. UV spectral data and melting curves do not reveal differences in the reactivity of these complexes with DNA. This and other features are correlated with the stability of the complexes studied.

Spectral and luminescent properties of mixed-ligand complexes of palladium(II) and 7,8-benzoquinoline

Spectral and luminescent properties of mixed-ligand palladium(II) complexes—[PdBhq(μ-Cl)]2, [PdBhqEn]ClO4, and [PdBhqBpy]ClO4, where Bhq stands for the 7,8-benzoquinoline ion—were studied. The absorption spectra of these complexes in the 25000–40000-cm− range were found to have a number of spin-allowed transitions of the 1(π-π*) type involving orbitals of the 7,8-benzoquinoline ligand. The luminescent characteristics of these compounds in a glass-forming matrix at 77 K are primarily determined by the participation of the 3(π-π*) states of the 7,8-benzoquinoline ligand.