Pure Ligands Research Articles

Regioselective Photochemical Cycloaddition Reactions of Diolefinic Ligands in Coordination Polymers.

The pure diolefinic ligand 1,4-bis(pyridin-4-yl)-1,3-butadiene (bpbde) is photostable in the crystalline state. With the assistance of coordination-driven metal-organic assemblies, the photoreactivity of this diolefinic ligand can be significantly enhanced. A hydrothermal reaction of bpbde with Cd(NO3 )2 ⋅4 H2 O and the auxiliary ligand adipic acid resulted in the formation of a two-dimensional photoreactive coordination polymer (CP), [Cd(adipate)(bpbde)]n (1). When the aliphatic carboxylic acid was replaced by pimelic acid, another photoreactive CP [Cd(pimelate)(bpbde)]n (2) with a three-dimensional framework was obtained. With irradiation of 365 nm UV light, the bpbde ligands in crystalline 1 and 2 underwent a regioselective photochemical [2+2] cycloaddition reaction and converted to 3,4,7,8-tetra(pyridin-4-yl)tricyclo[4.2.0.02,5 ]octane (tptco) and 1,3-bis(pyridin-4-yl)-2,4-bis(2-(pyridin-4-yl)vinyl)cyclobutane (bpbpvcb), respectively. The results provide an interesting insight into the rational design of highly regio- or stereoselective photocatalytic reactions for the formation of special organic molecules.

Partitioning surface ligands on nanocrystals for maximal solubility

A typical colloidal nanoparticle can be viewed as a nanocrystal-ligands complex with an inorganic single-crystalline core, the nanocrystal, bonded with a monolayer of organic ligands. The surface chemistry of nanocrystal-ligands complexes is crucial to their bulk properties. However, deciphering the molecular pictures of the nonperiodic and dynamic organic-inorganic interlayer is a grand technical challenge, and this hampers the quantitative perception of their macroscopic phenomena. Here we show that the atomic arrangement on nanocrystal surface and ligand-ligand interactions can be precisely quantified through comprehensive solid-state nuclear magnetic resonance (SSNMR) methodologies. The analyses reveal that the mixed ligands of n-alkanoates on a CdSe nanocrystal segregate in areal partitions and the unique arrangement unlocks their rotational freedom. The mathematical model based on the NMR-derived ligand partition and dynamics successfully predicts the unusual solubility of nanocrystal-ligands complexes with mixed ligands, which is several orders of magnitude higher than that of nanocrystal-ligands complexes with pure ligands.

Synthesis and characterization of new galactosylated-based N2O-donors tridentate ligands

AbSTRACTThe synthesis and characterization of three novel N2O-donor ligands containing the group 4-[1-β-d-2,3,4,6-tetra-O-acetyl-galactosyl)]benzaldehyde are presented. The insertion of this group was designed to increase the absorption of the prodrug in tumor cells, and is part of an ongoing work in our group with tridentate ligands to develop potential cobalt(III) prodrugs. The synthetic route described here allowed the isolation of pure ligands with yields ranged 81-89%. Finally, compounds were characterized by IR, NMR and HRMS (ESI+).

Iridium complexes with P-stereogenic phosphino imidazole ligands: Synthesis, structure and catalysis

The synthesis of optically and diastereomerically pure P-stereogenic phosphine-imidazole ligands is reported. The new ligands contain either a benzoimidazole or a 4-phenylimidazole as a N-donor fragment. The ligands have been coordinated to iridium and the structure of the corresponding cationic COD complexes has been determined by X-ray analysis. The combination of the chiral phosphorus atom and the imidazole substituents generate a strong chiral environment around the metal center. Preliminary hydrogenation reactions with a model cyclic β-enamide are also reported.

From Alkane to Alkene: The Inert Aliphatic C–H Bond Activation Presented by Binuclear Iron Stearoyl-CoA Desaturase with a Long di-Fe Distance of 6 Å

The desaturation of inert aliphatic C–H bonds from alkane to alkene, the initial step in biological fatty acid metabolism, can be catalyzed by a nonheme di-iron (NHFe2) stearoyl-CoA desaturase (SCD1) with the longest di-Fe distance of >6 Å known in NHFe2 enzymes. The SCD1 di-iron core is devised by nine histidines with penta- (FeA) and tetra-coordinations (FeB) mixed. Utilizing density functional theory calculations, we demonstrate that SCD1 employs a mechanism unknown previously in other NHFe2 enzymes, which involves the binding of O2/water leading to FeA(II)-•OH + FeB(II)-•OOH, the addition of H+/e forming FeA(II)-water, the O–O bond dissociation assisted by a hydrogen transfer from FeA(II)-water to FeB-bound oxygen to form a unique triple-hydroxyl intermediate of FeA(II)-•OH + FeB(II)-(•OH)2, a hydrogen transfer inside FeB(II)-(•OH)2 resulting in a FeA(II)-•OH and a high-valent FeB(IV)═O, the respective abstraction of the C9- and C10-hydrogens of substrates by FeB(IV)═O and FeA(II)-•OH producing alkene, and the regeneration of FeB(II)-•OH to FeB(II)-(OH2)2 with another H+/e added. The remote di-iron mixed with penta- and tetra-coordinations cooperates closely and achieves a good reactivity balance between O–O dissociation and hydrogen abstraction. The activity order of various Fe-containing species in the aliphatic C–H bond activation was obtained. Other important mechanistic characteristics and chemistry were also revealed. Our investigation lays a foundation for the design of low-cost and easily synthesized biomimetic catalysts for the aliphatic C–H bond activation, such as homogeneous di-Fe(II) complexes with pure N-containing ligands and heterogeneous porous Fe(II)-N metal–organic frameworks.

Construction of High‐Quality Cu(I) Complex‐Based WOLEDs with Dual Emissive Layers Achieved by an “On‐and‐Off” Deposition Strategy

AbstractInexpensive and highly luminescent Cu(I) complexes exhibit great potential as emitters in organic light‐emitting diodes (OLEDs), especially in white OLEDs (WOLEDs). In this work, two compounds 9‐(3‐(quinolin‐4‐yl)phenyl)‐9H‐carbazole (CzPQ) and 9,9′‐(quinoline‐4,6‐diylbis(3,1‐phenylene))bis(9H‐carbazole) (2CzPQ) are designed and synthesized to form Cu(I) complexes in situ by codeposition with copper iodide (CuI). The corresponding OLEDs show an orange red emission with a maximum external quantum efficiency (EQE) of 6.7%. Based on this result, an “on‐and‐off” strategy is proposed to achieve WOLEDs with the combination of Cu(I) complex layer and the pure ligand layer by controlling the shutter of CuI source on and off. The optimized WOLEDs give a maximum EQE of 2.4% with excellent Commission Internationale de L'Eclairage (CIE) coordinates of (0.32, 0.33) and a remarkable color‐rendering index (CRI) of 94. It can be forecasted that the device efficiency would be improved by tuning the chemical structure of the ligand.

In situ generated pyroglutamate bridged polyoxotitaniums with strong circular dichroism signal

In this text, we use inexpensive and natural amino acid, successfully obtained the asymmetric crystallization of three PTCs, [Ti6(OiPr)14(μ2-O)(μ3-O)2(d/l-pGlu)2] (d-PTC-53; l-PTC-53; H2pGlu = pyroglutamic acid) and [Ti6(OiPr)14(μ2-O)(μ3-O)2(d-pGlu)2] [Ti6(OiPr)14(μ2-O)(μ3-O)2(l-pGlu)2] (d,l-PTC-53). Interestingly, in situ lactamide reaction starting from glutamic acid to pyroglutamic acid was observed. In addition, the chirality features of these PTCs have been thoroughly discussed. The two enantiomers crystallize in chiral P21 space group. The optically pure pGlu ligands transform its chirality to the inorganic titanium oxo clusters. As a result, the stack of these inorganic clusters generates homochiral helical chains along the characteristic axial direction. Apart from the microscopic structural analysis, the macroscopic solid-state samples exhibit unusual strong circular dichroism (CD) signals, further verified the homochiral feature of the enantiomers.

Copper(ii)-based coordination polymer nanofibers as a highly effective antibacterial material with a synergistic mechanism.

Nanofibers of a copper(ii)-based coordination polymer [Cu(HBTC)(H2O)3] were synthesized via a microwave-assisted hydrothermal process, while macroparticles and bulk crystals were prepared via a hydrothermal method. X-ray analysis revealed that this compound possesses one-dimensional zig-zag chains, in which the coordination polyhedron of the copper(ii) center is a five-coordinate distorted square-pyramid. The width of the as-prepared nanofibers was about 150 nm, while the size of the macroparticles was about 200 μm. The antibacterial activities of the nanofibers and macroparticles against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated by determining the minimal inhibitory concentration (MIC), the growth curve of the bacteria and the bacterial reduction assay. The nanofibers showed higher antibacterial performance as compared with macroparticles, commercial copper nanoparticles, and pure ligands alone. The bacteriostatic rates of nanofibers and macroparticles were up to 99.9% and 96.7% against E. coli, while 99.1% and 96.2% against S. aureus, respectively, when the concentration was 250 μg mL-1. The synergistic antibacterial mechanism was also proposed based on the generation of reactive oxygen species (ROS) and the release of Cu2+ ions.

Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics.

Although natural herbs have been a rich source of compounds for drug discovery, identification of bioactive components from natural herbs suffers from low efficiency and prohibitive cost of the conventional bioassay-based screening platforms. Here we develop a new strategy that integrates virtual screening, affinity mass spectrometry (MS) and targeted metabolomics for efficient discovery of herb-derived ligands towards a specific protein target site. Herb-based virtual screening conveniently selects herbs of potential bioactivity whereas affinity MS combined with targeted metabolomics readily screens candidate compounds in a high-throughput manner. This new integrated approach was benchmarked on screening chemical ligands that target the hydrophobic pocket of the nucleoprotein (NP) of Ebola viruses for which no small molecule ligands have been reported. Seven compounds identified by this approach from the crude extracts of three natural herbs were all validated to bind to the NP target in pure ligand binding assays. Among them, three compounds isolated from Piper nigrum (HJ-1, HJ-4 and HJ-6) strongly promoted the formation of large NP oligomers and reduced the protein thermal stability. In addition, cooperative binding between these chemical ligands and an endogenous peptide ligand was observed, and molecular docking was employed to propose a possible mechanism. Taken together, we established a platform integrating in silico and experimental screening approaches for efficient discovery of herb-derived bioactive ligands especially towards non-enzyme protein targets.

Alkali metal complexes of an enantiopure iminophosphonamide ligand with bright delayed fluorescence.

The enantiomerically pure ligand P,P-diphenyl-N,N'-bis((R)-1-phenylethyl)phosphinimidic amide (1; (R)-HPEPIA) was synthesized and subsequently deprotonated with alkali metal precursors to yield dimeric complexes [M2{(R)-PEPIA}2] (M = Li (2), Na (3), K (4), Rb (5)). The cesium compound [M{(R)-PEPIA}] (6) crystallized as a cocrystal composed of dimeric ([Cs2{(R)-PEPIA}2] (6d ) and 1D-polymeric ([Cs{(R)-PEPIA}] n ) (6p ) species in a 1 : 1 ratio. The coordination polymer 6p features a unique sinus-shaped configuration of repeating -Cs-N-P-N-Cs-N-P-N- units. Unusual photoluminescence (PL) properties were found for solid 1-6: in contrast to the fluorescent ligand 1, the alkali metal complexes show phosphorescence at low temperatures (<100 K) and thermally activated delayed fluorescence (TADF) above ∼150 K. The latter provides for PL quantum yields up to 36% (3) at ambient temperature. DFT calculations support that both 1 and 2-6d have similar singlet and triplet excited states with energy separations of a few tens of meV. The strongly enhanced intersystem crossing (ISC) in the metal complexes, resulting in TADF, is attributed to their dimeric structure. This suggests that the fluorophore dimerization may serve as a tool to effect ISC for the design of TADF emitters.

Ternary complexes consisting of chiral rhodium(II) tetracarboxylates, derivatives of amino acid and triphenylphosphine: The 31P NMR study

Thirteen ternary complexes of optically pure chiral rhodium(II) tetracarboxylates with chiral ligands and triphenylphosphine, formed in situ in CDCl3 solution, were examined by nuclear magnetic resonance spectroscopy. As chiral substrates, two dimeric rhodium tetracarboxylates, derivatives of Mosher's acid and N-phthaloyl tert-leucine, were used. Two chiral amines, N,N-dimethyl-butan-2-amine and N,N-dimethyl-1-phenylethanamine, and some derivatives of methionine, selenomethionine, S-methylcysteine, leucine and proline, were applied as chiral ligands, both optically pure and racemic. An achiral component of ternary complexes, triphenylphosphine, acted as a 31P NMR probe.Ternary complexes containing optically pure ligands revealed 31P NMR signals (233 K, CDCl3) within the range from ca. −24 to −36 ppm, appearing as doublets due to 1J(103Rh,31P) coupling constants of ca. 90 Hz. For some combinations of racemic ligand and dirhodium tetracarboxylate, the signals appeared as quartets due to the presence of two diastereomeric ternary complexes. In these cases, diastereomeric dispersion varied from 14 to 88 Hz. Such signal splitting was not observed for the corresponding complexes of optically pure ligands. The presence of bulky substituents in rhodium tetracarboxylate increases diastereomeric dispersion. These results suggested that ternary complexes in question, in combination with 31P NMR technique, can serve, in some cases, as a means of the optical purity analysis of chiral ligands.

A new class of well-defined ruthenium catalysts for enantioselective transfer hydrogenation of various ketones

A pair of novel optically pure phosphinite ligands were synthesized by ring opening reaction of chiral amines with (R)-styrene oxide or (S)-glycidyl phenyl ether oxide using a straightforward method in high yields and their ruthenium complexes were described in detail. The ruthenium complexes proved to be highly efficient catalysts for the enantioselective hydrogenation of ketones, affording products up to 99% ee. The results showed that the corresponding chiral alcohols could be obtained with high activity and excellent enantioselectivities at the desired temperature. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinito[dichloro(η6-benzene)ruthenium (II)] acts an excellent catalyst in the reduction of ketones, giving the corresponding alcohol up to 99% ee.

Near-Infrared Photoluminescence and Reversible Trans-to-Cis Photoisomerization of Mononuclear and Binuclear Ytterbium(III) Complexes Functionalized by Azobenzene Groups.

Two mononuclear and one binuclear ytterbium complexes with dual near-infrared (NIR) photoluminescence and reversible trans-to-cis photoisomerization functions were synthesized and characterized. The central ytterbium(III) ion coordinates with two β-diketonate (4,4,4-trifluoro-1-phenylbutane-1,3-dionate (tfd)) ligands and one deprotonated azobenzene-containing tetradentate ligand [(E)-4-(phenyldiazenyl)-N,N-bis(pyridin-2-ylmethyl) benzohydrazide (HL), (E)-4-((4-(dimethylamino)phenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)benzohydrazide (HNL), or (E)-4,4′-N′,N′-bis(pyridin-2-ylmethyl)benzohydrazide azobenzene (H2DL)] to form a neutral ternary complex ([Yb(tfd)2L], [Yb(tfd)2(NL)], or [Yb2(tfd)4(DL)], respectively), where the ytterbium(III) ion is eight-coordinated to N3O5 donor sets. X-ray crystallographic analysis shows that all three complexes form a trigonal dodecahedron geometry with similar −N=N– distances that are slightly longer than those of the pure azobenzene-containing ligands. The NIR luminescence properties of the Yb(III) complexes were determined at a wavelength of about 980 nm with quantum yields in the range of 0.4–0.6% in ethanol and acetonitrile solutions at room temperature, and trans-to-cis photoisomerization was determined with the quantum yields (Φt→c = 10–2) at the same level as their pure ligands. The trans-to-cis photoisomerization rates of the complexes (10–4 s–1) are slightly higher than those of the pure ligands and similar to azobenzene (10–5 to 10–4 s–1). From time-dependent density functional theory calculations of the energy levels of the first excited triplet states of the ligands, the energies of the lowest excited triplet states of all of the ligands are higher than the resonance level of Yb3+ (2F5/2, 1.2722 eV). We suggest that these azo-containing ligands may participate in energy transfer to the ytterbium ion, in addition to the main “antenna effect” ligand tfd. This is the first report of azobenzene group-functionalized ytterbium complexes with dual NIR luminescence and photoisomerization properties, indicating that azobenzene-containing lanthanide(III) complexes have potential applications as dual function materials in biological systems.

Reactions of [(dpp-Bian)Ln(dme)2] (Ln = Eu, Yb) with some oxidants

Europium and ytterbium complexes [(dpp-Bian)Ln(dme)2] (Ln=Eu (1), Yb(2), dme=1,2-dimethoxyethane) with redox-active dianionic 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene ligand (dpp-Bian) have been tested in the reactions with nitrous oxide and sulfur. The reactions performed in 1:1M ratio afford quantitatively neutral dpp-Bian, while the use of a half equivalent of oxidants leads to the europium complex with two radical-anionic dpp-Bian ligands [(dpp-Bian)2Eu(dme)] (3) and the known ytterbium ionic compound [(dpp-Bian)2Yb]−[(dpp-Bian)Yb(dme)2]+ (4). The same products have been produced by the treatment of 1 and 2 with dpp-Bian. The oxidation of 1 and 2 with either sulfur dioxide or sulfur diimide (Me3SiN=)2S proceeds with the total release of the neutral dpp-Bian. DFT calculations performed for 1 and 2 show pure ligand nature of the frontier molecular orbitals in both cases.

Two Stereoinduction Events in One C−H Activation Step: A Route towards Terphenyl Ligands with Two Atropisomeric Axes

AbstractHerein we disclose the synthesis of original chiral scaffolds—ortho‐orientated terphenyls presenting two atropisomeric Ar–Ar axes. These unusual structures were built up by using the C−H activation approach, and remarkably, both chiral axes were controlled with excellent stereoselectivity in a single transformation. During the reaction, not only does atroposelective functionalization of a biaryl precursor occur to establish one stereogenic axis, but an unprecedented atropo‐stereoselective C−H arylation also takes place to generate the second stereogenic element. These enantiomerically pure ortho‐terphenyls show an original tridimensional structure and thus constitute a unique foundation for building up a library of enantiomerically pure bidentate ligands, such as the new ligands S/N‐Biax and diphosphine BiaxPhos.

Two Stereoinduction Events in One C-H Activation Step: A Route towards Terphenyl Ligands with Two Atropisomeric Axes.

Herein we disclose the synthesis of original chiral scaffolds-ortho-orientated terphenyls presenting two atropisomeric Ar-Ar axes. These unusual structures were built up by using the C-H activation approach, and remarkably, both chiral axes were controlled with excellent stereoselectivity in a single transformation. During the reaction, not only does atroposelective functionalization of a biaryl precursor occur to establish one stereogenic axis, but an unprecedented atropo-stereoselective C-H arylation also takes place to generate the second stereogenic element. These enantiomerically pure ortho-terphenyls show an original tridimensional structure and thus constitute a unique foundation for building up a library of enantiomerically pure bidentate ligands, such as the new ligands S/N-Biax and diphosphine BiaxPhos.

Synthesis, characterization and determination of absolute structures of palladium complexes of novel chiral acyclic tellurated Schiff base ligands

Enantiomerically pure chiral hybrid organotellurium ligands and their asymmetric palladium complexes have been synthesized and characterized.

Versatile Tailoring of NH2 -Containing Metal-Organic Frameworks with Paddle-Wheel Units.

An amine-containing non-interpenetrating pillar-layer framework, [Zn2 (dbtcb)(L1)]⋅x solvent (1), has been synthesized from Zn(NO3 )2 and the ligands 1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene (H4 DBTCB) and 2,5-bis(4-pyridyl)aniline (L1). The [Zn2 (COO)4 ] secondary building units (SBUs) are bridged by DBTCB to form two-dimensional layers that are linked by L1 ligands acting as pillars to form a three-dimensional network. This NH2 -containing framework can undergo versatile tailoring through post-synthetic covalent modification, solvent-assisted linker exchange (SALE), and single-crystal-to-single-crystal (SC-SC) transmetalation reactions. Acetamide-functionalized [Zn2 (L2)(dbtcb)]⋅xsolvent (2) could be obtained by direct synthesis from Zn(NO3 )2 , N-acetyl-2,5-bis(4-pyridyl)aniline (L2) and H4 DBTCB. Importantly, compound 1 with pure NH2 ligands as pillars could be obtained by SALE of 2 with L1 in DMSO solution. The transmetalation reactions of 1 with CuII , NiII , and CoII were studied; inductively coupled plasma-atomic emission (ICP) analysis revealed that 1 underwent almost complete SC-SC transmetalation with CuII within 30 h, whereas with NiII and CoII only 70 and 80 % substitutions were achieved. Photoluminescence studies revealed that 1 and 2 display yellow-green and UV emission, respectively, under a UV lamp. Furthermore, the photoluminescent properties could be tuned by introducing mixed pillar amino ligands L1 and L2 into the MOF to produce multivariate (MTV) MOF 3 displaying overall orange emission.

Copper Guanidinoquinoline Complexes as Entatic State Models of Electron‐Transfer Proteins

The electron-transfer abilities of the copper guanidinoquinoline (GUAqu) complexes [Cu(TMGqu)2 ]+/2+ and [Cu(DMEGqu)2 ]+/2+ (TMGqu=tetramethylguanidinoquinoline, DMEGqu=dimethylethylguanidinoquinoline) were examined in different solvents. The determination of the electron self-exchange rate based on the Marcus theory reveals the highest electron-transfer rate of copper complexes with pure N-donor ligands (k11 =1.2×104 s-1 m-1 in propionitrile). This is supported by an examination of the reorganisation energy of the complexes by using Eyring theory and DFT calculations. The low reorganisation energies in nitrile solvents correspond with the high electron-transfer rates of the complexes. Therefore, the [Cu(GUAqu)2 ]+/2+ complexes act as good entatic states model of copper enzymes. The structural influence of the complexes on the kinetic parameters shows that the TMGqu system possesses a higher electron-transfer rate than DMEGqu. Supporting DFT calculations give a closer insight into the kinetics and thermodynamics (Nelsen's four-point method and isodesmic reactions) of the electron transfer.

PRR signaling during in vitro macrophage differentiation from progenitors modulates their subsequent response to inflammatory stimuli.

Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage in vitro and also in vivo following infection. In this study, we used an in vitro model of HSPC differentiation to investigate the functional consequences (cytokine production) that exposing HSPCs to various pathogen-associated molecular patterns (PAMPs) and Candida albicans cells have on the subsequently derived macrophages. Mouse HSPCs (Lin- cells) were cultured with GM-CSF to induce macrophage differentiation in the presence or absence of the following pattern recognition receptor (PRR) agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or inactivated C.albicans yeasts (which activate several PRRs, mainly TLR2 and Dectin-1). Our data show that only pure TLR2 ligand exposure (transient and continuous) impacts the inflammatory function of GM-CSF-derived macrophages, because Pam3CSK4-exposed HSPCs generate macrophages with a diminished ability to produce inflammatory cytokines. Interestingly, the Pam3CSK4-induced tolerance of macrophages (by transient exposure of HSPCs) is reinforced by subsequent exposure to C.albicans cells in GM-CSF-derived macrophages; however, the induced tolerance is partially reversed in M-CSF-derived macrophages. Therefore, the ability of macrophages to produce inflammatory cytokines is extremely dependent on how the HSPCs from which they are derived receive and integrate multiple microenvironmental signals (PRR ligands and/or CSFs).