Labile Ligands Research Articles

Synthesis and Biological Activity of Gold(I) N‐Heterocyclic Carbene Complexes with Long Aliphatic Side Chains

AbstractSeven imidazolium salts have been synthesized from octadecylimidazole (Im18). These salts differ in the length of the alkyl chain length bound to the second nitrogen atom of the imidazolium ring [R = Me, Et, iPr, Pr, Bu, decyl (Dec), octadecyl] and were used as synthetic precursors to obtain two series of gold(I) carbene complexes (AuNHC). The first series contains one labile ligand at the second coordinative position {monocarbene, [AuCl(NHC)]}, and the second one comprises dicarbene complexes. Their biological activity has been evaluated with respect to two different cell lines, and thioredoxin reductase (TrxR) inhibition has also been evaluated for selected examples. Distinct effects have been observed for the imidazolium salts and monocarbene derivatives.

Role of the base in Buchwald-Hartwig amination.

The Buchwald-Hartwig amination has been investigated theoretically and experimentally to examine the scope of possible bases under different reaction conditions. Nonpolar solvents resist the formation of new charges. Therefore, the base should be anionic to be able to deprotonate the neutral palladium-amine complex and/or expel the anionic leaving group (bromide). The calculated barrier for the organic base DBU was found to be prohibitively high. In polar solvent, dissociation of bromide becomes possible, but here the base will instead form a complex with palladium, creating an overly stable resting state. The conclusions for both solvent classes hold for both a hindered monodentate phosphine and the labile bidentate ligand BINAP. The computational studies were supported by experimental testing of a range of bases using BINAP in two different solvents, toluene and DMF.

Isotropic exchange interaction between Mo and the proximal FeS center in the xanthine oxidase family member aldehyde oxidoreductase from Desulfovibrio gigas on native and polyalcohol inhibited samples: an EPR and QM/MM study.

Aldehyde oxidoreductase from Desulfovibrio gigas (DgAOR) is a homodimeric molybdenum-containing protein that catalyzes the hydroxylation of aldehydes to carboxylic acids and contains a Mo-pyranopterin active site and two FeS centers called FeS 1 and FeS 2. The electron transfer reaction inside DgAOR is proposed to be performed through a chemical pathway linking Mo and the two FeS clusters involving the pyranopterin ligand. EPR studies performed on reduced as-prepared DgAOR showed that this pathway is able to transmit very weak exchange interactions between Mo(V) and reduced FeS 1. Similar EPR studies but performed on DgAOR samples inhibited with glycerol and ethylene glycol showed that the value of the exchange coupling constant J increases ~2 times upon alcohol inhibition. Structural studies in these DgAOR samples have demonstrated that the Mo-FeS 1 bridging pathway does not show significant differences, confirming that the changes in J observed upon inhibition cannot be ascribed to structural changes associated neither with pyranopterin and FeS 1 nor with changes in the electronic structure of FeS 1, as its EPR properties remain unchanged. Theoretical calculations indicate that the changes in J detected by EPR are related to changes in the electronic structure of Mo(V) determined by the replacement of the OHx labile ligand for an alcohol molecule. Since the relationship between electron transfer rate and isotropic exchange interaction, the present results suggest that the intraenzyme electron transfer process mediated by the pyranopterin moiety is governed by a Mo ligand-based regulatory mechanism.

Making oxidation potentials predictable: coordination of additives applied to the electronic fine tuning of an iron(II) complex.

This work examines the impact of axially coordinating additives on the electronic structure of a bioinspired octahedral low-spin iron(II) N-heterocyclic carbene (Fe-NHC) complex. Bearing two labile trans-acetonitrile ligands, the Fe-NHC complex, which is also an excellent oxidation catalyst, is prone to axial ligand exchange. Phosphine- and pyridine-based additives are used for substitution of the acetonitrile ligands. On the basis of the resulting defined complexes, predictability of the oxidation potentials is demonstrated, based on a correlation between cyclic voltammetry experiments and density functional theory calculated molecular orbital energies. Fundamental insights into changes of the electronic properties upon axial ligand exchange and the impact on related attributes will finally lead to target-oriented manipulation of the electronic properties and consequently to the effective tuning of the reactivity of bioinspired systems.

Complexation of the (η5-Cp)Ru+ and (η5-Cp*)Ru+ Arenophiles on Alkynylnaphthalene: Solvent Effect on the Regioselectivity and the Haptotropic Rearrangement

The reactions of [Cp*Ru(NCMe)3](PF6) and 1,4-R-C6H4-C≡C-SiMe3 (R = Me, C≡C-SiMe3; Cp* = η5-C5Me5) in CH2Cl2 provided the complexes [Cp*Ru(η6-4-MeC6H4-C≡C-SiMe3)](PF6) (1) and [Cp*Ru(η6-1,4-C6H4(C≡C-SiMe3)2](PF6) (2) in 65% yield. A similar reaction using 1-(trimethylsilylethynyl)naphthalene provided the complexes [Cp*Ru(η6-C10H7(C≡C-SiMe3))](PF6), bearing the Cp*Ru+ arenophile on the monosubstituted (3A) or unsubstituted (3B) fused ring, in 86% yield. The 3A/3B kinetic ratio is 43/57, while the 3A/3B thermodynamic ratio is 27/73. The bis(alkynylnaphthalene) complexes [Cp*Ru(η6-1,4-C10H6(C≡C-SiMe3)2)](PF6) were also obtained in good yields with 4A/4B kinetic ratios ranging from 80/20 to 16/84 depending on the concentration of a labile ligand able to temporarily replace one acetonitrile ligand on [Cp*Ru(NCMe)3](PF6). In the absence of such a ligand the reaction did not take place. Isomer 4A can be quantitatively converted to the thermodynamic regioisomer 4B. The kinetic products were obtained in less than 4 h at temperatures ranging from −17 to 20 °C, while the isomerization is much slower. The thermodynamic equilibrium is reached after several days at 20 °C in a good coordinating solvent such as acetone. The bis(alkynylnaphthalene) was also reacted with [CpRu(NCMe)3](PF6) (Cp = η5-C5H5). The corresponding complexes 5A,B were isolated with an overall yield of 87% and 5A/5B kinetic ratios ranging from 5/95 to 20/80, while the thermodynamic ratio was 45/55. The experimental data analyzed with the support of theoretical calculations allowed us to propose a mechanism for the reactions of complexation and isomerization.

H-bonded adducts of [2,4,6-{(C10H21O)3C6H2NH}3C3N3] with [LnM{PPh2(C6H4CO2H)}] displaying Columnar Mesophases at Room Temperature

Displacement of a labile ligand from appropriate precursor complexes by 2- or 4-PPh2C6H4COOH yields neutral gold(I) and gold(III) [AuXn(PPh2C6H4COOH)] (n = 1, X = Cl; n = 3, X = C6F5), cationic gold(I) [Au(PPh2C6H4COOH)2](CF3SO3), and neutral chromium(0) [Cr(CO)5(PPh2C6H4COOH)] metallo-organic acids. [AuCl(4-PPh2C6H4COOH)], [Au(C6F5)3(4-PPh2C6H4COOH)], and [Cr(CO)5(2-PPh2C6H4COOH)] have dimeric structures with typical carboxylic H-bond bridges, whereas [Au(C6F5)3(2-PPh2C6H4COOH)] gives a monomeric species with the carboxylic acid H bonded to cocrystallized solvent molecules. All gold-containing acids are emissive at 77 K in the range 404-520 nm and some of them also at 298 K with emission maxima from 441 to 485 nm. Reaction of these acid metal complexes with the triazine mesogen 2,4,6-{(C10H21O)3C6H2NH}3C3N3 affords some new hydrogen-bonded gold(I) and chromium(0) supramolecular adducts, but the related gold(III) complexes do not form adducts. The 4-diphenylphosphinobenzoic adducts display a columnar hexagonal mesophase (Colhex) at room temperature, with a random one-dimensional stacking of the pseudo-discoid triazine-metallo-organic adducts into columns, where the metallo-phosphinoacid fragments act as the fourth branch of the trifold triazine core. The 2-diphenylphosphinobenzoic mixtures do not display mesophases, as they appear in the X-ray studies as mixtures of the triazine and the metallo-phosphinoacid complex. The aggregates are luminescent at 77 K, with emission maxima in the range 419-455 nm.

Cationic isonitrile complexes of the CpFe(CO)2 fragment

[CpFe(CO)2(THF)]+BF4− undergoes exchange of the labile THF ligand against isonitriles resulting in a shift of the NC-stretching vibration to higher energies compared to the free isonitriles. Quantum chemical calculations show that this shift is not a real indicator for the electronic character and thus the electronic influence of the substituents at the para-functionalized phenylisonitriles. In contrast, other calculated parameters such as reactions enthalpies, Fe–C distances, charges and CO-stretching frequencies clearly correlate with the Hammett constant σp.

Design, synthesis and SAR studies of novel 1,2-bis(aminomethyl)cyclohexane platinum(II) complexes with cytotoxic activity. Studies of interaction with DNA of iodinated seven-membered 1,4-diaminoplatinocycles

A selected library of nine novel platinum(II) complexes having differently functionalized 1,2-bis(aminomethyl)cyclohexane carrier ligands with a 1,4-diamino framework and iodides as labile ligands have been synthesized and evaluated in vitro for their tumor cell growth inhibitory activity, in front of one pair of human carcinoma cell lines A2780 and A2780cisR. These cell lines were chosen based on studying all the known main mechanisms of resistance of cisplatin. A2780cisR cells are resistant through a combination of reduced drug transport enhanced DNA repair/tolerance and elevated glutathione (GSH) levels with respect to the parental A2780 cells. Most platinum complexes evaluated showed a very low resistant factor, up to 16 times lower than that of cisplatin, which indicates their ability to overcome the cisplatin resistance in ovarian cancer A2780cisR cells. Structure–activity studies have been performed in order to know the influence of the several organic functionalities (CC double bond, free OH group, MeO group, etc.) and the stereochemistry on the cytotoxic activity. Moreover, studies of interaction with DNA of these complexes were performed via three techniques: circular dichroism (CD), electrophoresis on agarose gel (EF) and atomic force microscopy (AFM) in order to evaluate the modifications of secondary and tertiary structure of DNA, induced by platinum complexes. These studies allowed us to correlate the IC50 values of complexes and the intensity of interaction to DNA, the main target for these compounds.

Spin-state-associated ligand distortion and complex solution equilibrium for a pair of Fe(II) pyridyl-imidazoline complexes

Reported herein are the magnetic and structural properties as well as solution equilibrium investigation for a pair of iron (II) pyridyl-imidazoline complexes: [Fe(pizMe)Cl2]2 (1) and [Fe(pizMe)3](FeCl4) (2), where pizMe=2-(2′-pyridinyl)-4,5-dihydro-1-methylimidazole. Dinuclear complex 1 contains high-spin iron (II) centers and a “flat” pizMe ligand (planar at the imidazoline N atom), while the pizMe-containing complex in 2 exhibits characteristics of a low-spin iron (II) center and a pyramidalized pizMe ligand. In solution, the two complexes are present in equilibrium as evinced through NMR and electronic absorption spectral studies. Spin-state switching between 1 and 2 in methanolic solution is a result of ligand lability.

Peripheral Methyl Activation in η4-1,2,3,4-Tetramethylcyclobutadienylcobalt Complexes: Template Synthesis and Subsequent Reactivity of Triphosphamacrocycles

The cationic complex (η4-1,2,3,4-tetramethylcyclobutadienyl)cobalt(trisacetonitrile), [(η4-C4Me4)Co(NCCH3)3]+ (1), allows the stepwise introduction of suitable phosphine precursors to the [(η4-C4Me4)Co]+ fragment by replacement of the labile acetonitrile ligands. These reactions give rise to the piano-stool complexes [(η4-C4Me4)Co(dppe)(NCCH3)]+ (2), [(η4-C4Me4)Co(dppe)(PH2Ph)]+ (3), [(η4-C4Me4)Co(dfppb)(NCCH3)]+ (4), and [(η4-C4Me4)Co(dfppb)(PH2Ph)]+ (5), where dfppb = 1,2-bis{di(2-fluorophenyl)phosphino}benzene and dppe = 1,2-bis(diphenylphosphino)ethane. Complex 5 is a template for the synthesis of the P3 macrocycle complex [(η4-C4Me4)Co{1,4-bis(2-fluorophenyl)-7-phenyl[b,e,h]tribenzo-1,4,7-triphosphacyclononane}]+ (6), through base-promoted intramolecular macrocyclization. The hydrogens of two of the ring methyls of the tetramethylcyclobutadienyl ligand in the macrocycle complex 6 are sufficiently acidic to undergo deprotonation by KOtBu, promoting nucleophilic attack at the fluorine-bearing ortho-carbons of the 2-fluoroaryl groups on two of the phosphorus donors in 6. The resultant hemi-incarcerand complex [{η4,κP,κP,κP-Me2C4-[1,4-bis(2-CH2C6H4)-7-C6H5-[b,e,h]tribenzo-1,4,7-triphosphacyclononane]-1,2}Co]+ (cis-7) contains a hybrid phosphorus/carbon donor ligand where the P3 macrocycle is connected to the cyclobutadienyl function through two cis-2-methylphenyl links. The new complexes have been characterized fully by spectroscopic and analytical techniques including single-crystal X-ray structure determinations of 2, 3, 4, 5, 6, and cis-7.

Solution and solid state effects of coordinated ligands in rhenium (I) complexes

In the last few years the coordination chemistry of rhenium and technetium has gained major interest for the possible use in radiopharmacy, due to its compact size, its low positive charge, coordination properties, d6 low-spin configuration and significant stability. This interest was further fuelled when Alberto remarkably synthesized fac-[99mTc-(CO)3(H2O)3] from [99mTcO4]- in aqueous medium and under mild conditions. Several fac-[M(CO)3]+ (M = Re, 99mTc) type complexes have been synthesized to date with a large number of ligand systems.[1,2] The three labile aqua ligands on the starting synthon fac-[Re(CO)3(H2O)3]+ can easily be substituted by a variety and/or combinations of ligands producing stable compounds and potential radiopharmaceuticals with many different characteristics. Our interest focuses on the fac-[Re(CO)3]+ moiety and related compounds by adopting the [2+1] approach.[3] The solid state behaviour of the complexes are explored as well as different effects such as the charge of the complexes as well as the effect of different types of donor atoms and electron donating or withdrawing systems. The influence of coordinated bidentate ligands on the rate of substitution in solution, by a variety of entering ligands, is also investigated. Crystal structures of Re(I) tricarbonyl tropolonato complexes with various monodentate incoming ligands were obtained in the study and will form part of this presentation.

Mesoionic Triazolylidene Nickel Complexes: Synthesis, Ligand Lability, and Catalytic C–C Bond Formation Activity

A set of triazolylidene (trz) nickel(II) complexes [NiCpX(trz)] was synthesized by a direct metalation of the corresponding triazolium salt with nickelocene, NiCp2. While at short reaction times and in the presence of a coordinating anion X the mono-carbene complex is preferably formed, long reaction times induce the gradual transformation of [NiCpX(trz)] to the bis-carbene complexes [Ni(Cp)(trz)2]+. Kinetic analyses lend strong support to a consecutive pathway involving triazolylidene dissociation from [NiCpX(trz)] en route to the bis-carbene complex. Similar carbene transfer is observed in a solid-state reaction upon heating the complex [NiCpI(trz)] in vacuo, which induces disproportionation to [NiI2(trz)2] and NiCp2, confirming that the Ni–C(trz) bond is kinetically labile. The complexes [Ni(Cp)(trz)2]+ and [NiCpX(trz)] were both efficient catalyst precursors for Suzuki–Miyaura cross-coupling of aryl bromides and phenylboronic acid, with turnover frequencies exceeding 228 h–1. Complex degradation after short reaction times, identified in separate experiments, prohibits high turnover numbers, and for high conversions, repetitive additions of triazolylidene nickel complex and phenylboronic acid are necessary.

Homoleptic Molybdenum Cluster Sulfides Functionalized with Noninnocent Diimine Ligands: Synthesis, Structure, and Redox Behavior

AbstractThiourea (tu) has been coordinated to the Mo3S44+ cluster unit to afford the new cluster compound [Mo3S4(tu)8(H2O)]Cl4·4H2O (1). The high substitutional lability of the thiourea ligands can be exploited to achieve smooth ligand substitution in the Mo3S4 cluster. The reactions of 1 with 1,10‐phenanthroline (phen) and 2,2′‐bipyridine (bpy) have resulted in new trisubstituted diimino complexes [Mo3S4Cl3L3]+ [L = phen (2), bpy (3)]. The crystal structure of [Mo3S4Cl3(phen)3]Cl·4H2O was determined by X‐ray analysis. A solid‐state cyclic voltammetry study of 2 shows a ligand‐centered reversible two‐electron reduction. DFT calculations for [Mo3S4Cl3(phen)3]+ and the 2e‐reduced species [Mo3S4Cl3(phen)3]– support our interpretation of the reduction process. Compound 3 undergoes a reversible two‐electron reduction, which is more metal‐centered on the basis of DFT calculations.

Experimental and Theoretical Study of Gold(III)-Catalyzed Hydration of Alkynes

The properties of different Au(III) halo dithiocarbamate complexes of structure [AuX2(S2CN(R)2)] as suitable catalysts for the hydration reaction of phenylacetylene have been tested. Moderate catalytic activity was found for X = Cl, Br, while those compounds in which X = I, C6F5 are inert. A working mechanism involving the initial dissociation of a labile ligand (Cl or Br) followed by coordination and activation of the alkyne, solvent-assisted attack of water, and enol tautomerization has been proposed through computational studies.

ChemInform Abstract: Palladium‐Catalyzed Coupling Reaction of Perfluoroarenes with Diarylzinc Compounds.

This report describes the first Pd(0)-catalyzed cross-coupling of hexafluorobenzene (C6F6) with diarylzinc compounds to give a variety of pentafluorophenyl arenes. This reaction could be applied to other perfluoroarenes, such as octafluorotoluene, pentafluoropyridine, and perfluoronaphthalene, to give the corresponding polyfluorinated coupling products. The optimal ligand in this catalytic reaction was PCy3 , and lithium iodide was indispensable as an additive for the coupling reaction. One of the roles of lithium iodide in this catalytic reaction was to promote the oxidative addition of one C-F bond of C6F6 to palladium. Stoichiometric reactions revealed that an expected oxidative-addition product, trans-[Pd(C6F5)I(PCy3)2], generated from the reaction of [Pd(PCy3)2] with C6F6 in the presence of lithium iodide, was not involved in the catalytic cycle. Instead, a transient three-coordinate, monophosphine-ligated species, [Pd(C6F5)I(PCy3)], emerged as a potential intermediate in the catalytic cycle. Therefore, we isolated a novel Pd(II) complex, [Pd(C6F5)I(PCy3)(py)], in which pyridine (py) acted as a labile ligand to generate the transient species. In fact, in the presence of lithium iodide, this Pd(II) complex was found to react smoothly with diphenylzinc to give the desired pentafluorophenyl benzene, whereas the same reaction conducted in the absence of lithium iodide resulted in a decreased yield of pentafluorophenyl benzene, which indicated that the other role of lithium iodide was to enhance the reactivity of the organozinc species during the transmetalation step.

Electrochemical behavior of phosphine-substituted ruthenium(II) polypyridine complexes with a single labile ligand.

A series of phosphine-substituted ruthenium polypyridine complexes, cis(P,Cl)-[Ru(trpy)(Pqn)Cl]PF6 (cis-Cl), trans(P,MeCN)-[Ru(trpy)(Pqn)(MeCN)](PF6)2 (trans-PN), cis(P,MeCN)-[Ru(trpy)(Pqn)(MeCN)](PF6)2 (cis-PN), and [Ru(trpy)(dppbz)(MeCN)](PF6)2 (PP), were synthesized and crystallographically characterized (trpy = 2,2':6',2″-terpyridine, Pqn = 8-(diphenylphosphanyl)quinoline, and dppbz = 1,2-bis(diphenylphosphanyl)benzene). In electrochemical measurements for cis-PN and PP, the reduction of cis-PN resulted in the formation of trans-PN via cis-trans isomerization and that of PP proceeded via a two-electron-transfer reaction. The mechanism of the electrochemical behaviors is discussed through consideration of five-coordinated species, [Ru(trpy)(Pqn)](n+) or [Ru(trpy)(dppbz)](n+) (n = 0-2), formed by liberation of a monodentate labile ligand.

Synthesis, biological evaluation and SAR studies of novel bicyclic antitumor platinum(IV) complexes

The present study describes the synthesis, anticancer activity and SAR studies of novel platinum(IV) complexes having 1,2-bis(aminomethyl)carbobicyclic or oxabicyclic carrier ligands, bearing chlorido and/or hydroxido ligands in axial position and chlorido or malonato ligands in equatorial position (labile ligands). These complexes were synthetized with the aim of obtaining new anticancer principles more soluble in water and therefore more bioavailable. Several substitution patterns on the platinum atom have been designed in order to evaluate their antiproliferative activity and to establish structure–activity relationship rules. The synthesis of platinum(IV) complexes with axial hydroxyl ligands on the platinum(IV) were carried out by reaction of K2Pt(OH)2Cl4 with the corresponding diamines. The complexes with axial chlorido ligands on the platinum(IV) atom were synthesized by direct reaction of diamines with K2PtCl6. Carboxylated complexes were synthesized by the substitution reaction of equatorial chlorido ligands by silver dicarboxylates. The most actives complexes were those having malonate as a labile ligand, no matter of the structure of the carrier ligand. Regarding the influence of the structure of the non-labile 1,4-diamine carrier ligand on the cytotoxicity, it was found that the complexes having the more lipophilic and symmetrical bicyclo[2.2.2]octane framework were much more active than those having an oxygen or methylene bridge.

Spectroscopic and computational insight into the activation of O2 by the mononuclear Cu center in polysaccharide monooxygenases.

Strategies for O2 activation by copper enzymes were recently expanded to include mononuclear Cu sites, with the discovery of the copper-dependent polysaccharide monooxygenases, also classified as auxiliary-activity enzymes 9-11 (AA9-11). These enzymes are finding considerable use in industrial biofuel production. Crystal structures of polysaccharide monooxygenases have emerged, but experimental studies are yet to determine the solution structure of the Cu site and how this relates to reactivity. From X-ray absorption near edge structure and extended X-ray absorption fine structure spectroscopies, we observed a change from four-coordinate Cu(II) to three-coordinate Cu(I) of the active site in solution, where three protein-derived nitrogen ligands coordinate the Cu in both redox states, and a labile hydroxide ligand is lost upon reduction. The spectroscopic data allowed for density functional theory calculations of an enzyme active site model, where the optimized Cu(I) and (II) structures were consistent with the experimental data. The O2 reactivity of the Cu(I) site was probed by EPR and stopped-flow absorption spectroscopies, and a rapid one-electron reduction of O2 and regeneration of the resting Cu(II) enzyme were observed. This reactivity was evaluated computationally, and by calibration to Cu-superoxide model complexes, formation of an end-on Cu-AA9-superoxide species was found to be thermodynamically favored. We discuss how this thermodynamically difficult one-electron reduction of O2 is enabled by the unique protein structure where two nitrogen ligands from His1 dictate formation of a T-shaped Cu(I) site, which provides an open coordination position for strong O2 binding with very little reorganization energy.

ChemInform Abstract: The Stability of Organometallic Ligands in Oxidation Catalysis

AbstractReview: [64 refs.

ChemInform Abstract: Developments in the Biomimetic Chemistry of Cubane‐Type and Higher Nuclearity Iron‐Sulfur Clusters

AbstractReview: 169 refs.