Rigid Ligand Research Articles

Double-Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes.

Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO4 ] (tht=tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a zebrafish model. Their cytotoxicity and their mechanisms of action are different and involve apoptosis, necrosis, and DNA damage. The compounds presented herein are potent metal-based cytostatics displaying LD50 values from 3.5-38 μm in different tumor cell lines and induce double-strand DNA breaks (DSB) as shown by H2AX phosphorylation (γH2AX) at foci of DSBs.

Metal-metal multiple bond in low-valent diuranium porphyrazines and its correlation with metal oxidation state: A relativistic DFT study

To explore the uranium-uranium bonding nature, a ligated diuranium complex that could be experimentally possible would show features with no bridging ligand constraints (i.e. discrete or unsupported ligand), rigid ligand skeleton and suitable U-ligand bond. In this respect, we have designed and examined a series of diuranium diporphyrazines (Um2Pz2, m=II, III and IV) using relativistic density functional theory. Optimizations on all possible electron-spin isomers find that the triplet, quintet and quintet states are energetically lowest for Um2Pz2 (m=II, III and IV), respectively. They possess bond lengths of UU at 2.37, 2.46 and 2.91Å, bond orders of 3.48, 3.33 and 2.11, and stretching vibrational frequencies of 239, 172 and 108cm−1. Associated with the electronic-structure and QTAIM (quantum theory of atoms in molecules) analyses, a weak quadruple bond is suggested for the triplet state of UII2Pz2, and the triple and double bonds for UIII2Pz2, and UIV2Pz2, respectively. It shows that the uranium oxidation state approximately correlates with the number of multiple bonds.

Syntheses and structures of two new coordination polymers generated from a 4-aminotriazole-bridged organic ligand and CoII salts

Organic ligands and counter-anions influence the coordination spheres of metal cations and hence the construction of coordination polymers (CPs). The specific bent geometries of five-membered heterocyclic triazole bridging organic ligands are capable of generating CPs with novel patterns not easily obtained using rigid linear ligands. A multidentate 4-aminotriazole-bridged organic ligand, namely 4-amino-3,5-bis(4,3'-bipyridyl-5'-yl)-4H-1,2,4-triazole (L) has been prepared and used to synthesize two CoII coordination polymers, namely poly[[[μ2-4-amino-3,5-bis(4,3'-bipyridyl-5'-yl)-4H-1,2,4-triazole-κ2N:N']bis(methanol-κO)cobalt(II)] bis(perchlorate)], {[Co(C22H16N8)2(CH3OH)2](ClO4)2}n, (I), and poly[[μ3-4-amino-3,5-bis(4,3'-bipyridyl-5'-yl)-4H-1,2,4-triazole-κ3N:N':N'']dichloridocobalt(II)], [CoCl2(C22H16N8)]n, (II), using CoX2 salts [X = ClO4 for (I) and Cl for (II)] under solvothermal conditions. Single-crystal X-ray structure analysis revealed that they both feature two-dimensional networks. Cobalt is located on an inversion centre in (I) and in a general position in (II). In (I), L functions as a bidentate cis-conformation ligand linking CoII ions, while it functions as a tridentate trans-conformation linker binding CoII ions in (II). In addition, O-H...N and N-H...O hydrogen bonds and C-H...π interactions exist in (I), while N-H...Cl and π-π interactions exist in (II), and these weak interactions play an important role in aligning the two-dimensional nets of (I) and (II) in the solid state. As the compounds were synthesized under the same conditions, the significant structural variations between (I) and (II) are believed to be determined by the different sizes and coordination abilities of the counter-anions. IR spectroscopy and diffuse reflectance UV-Vis spectra were also used to investigate the title compounds.

N-Decyl-S-trityl-(R)-cysteine, a new chiral selector for “green” ligand-exchange chromatography applications

In search for new enantioselectivity profiles, the N-decyl-S-trityl-(R)-cysteine [C10-(R)-STC] was synthesized through a one-step procedure and then hydrophobically adsorbed onto an octadecylsilica surface to generate a stable chiral stationary phase for ligand-exchange chromatography (CLEC-CSP) applications. The CLEC analysis was carried out on underivatized amino acids, by using a Cu(II) sulphate (1.0mM) containing aqueous eluent system. Most of the analysed compounds (34 out of 45) were enantiodiscriminated by the C10-(R)-STC-based CSP, with resolution factor (RS) values up to 8.86. Conformationally rigid and hydrophobic ligands often experienced the largest enantioselectivity effects. A high loadability emerged from the analysis of rac-NorVal (selected as prototype test compound): up to 20mg/mL were efficiently enantioseparated with the CLEC-CSP. Two in-line hand-made cartridges filled with a strong cation-exchange resin allowed the effective catching of Cu(II) ions after the semi-preparative enantioseparation. The quantitative recovery of the rac-NorVal enantiomers was made possible by flowing through the cartridge a 5% (v) ammonia solution. The CLEC phase proved successful in the enantioselective analysis of a commercially available (S)-Leu containing tablet. Furthermore, in order to understand the molecular basis for a successful use of the C10-(R)-STC-based CLEC system, a descriptive structure-separation relationship study was performed. As a result, all compounds with a MEAN-QPlogS (a hydrophilicity descriptor) value lower than 0.373 can be most likely enantioseparated with the CLEC system under investigation. In the work, the numerous aspects complying with the principles of green chromatography are highlighted and discussed.

Synthesis and structural characterization of two copper complexes with long rigid ligands

Two copper complexes with long rigid ligands, Cu(Tta)2(L1) (I), and Cu(Tta)2(L2) (II), where L1 = (E)-3-(4-(1H-benzo[d]imidazol-1-yl)-(4-phenyl)phenyl)-1-phenylprop-2-en-1-one, L2 = (E)-3-(4-(1H-imidazol-1-yl)phenyl)-1-(4-phenyl)phenyl)prop-2-en-1-one), have been synthesized and characterized. The single-crystal X-ray analysis (CIF files CCDC nos. 1409671 (I) and 1409672 (II)) for complexes I and II demonstrates that each copper ion assumes a distorted square-pyramidal MO4N polyhedron in which four oxygen atoms come from the Tta ligands, and one nitrogen atom comes from the N-donor ligand. Both of the complexes are linked into 3D networks through weak intermolecular interactions.

Structure and properties of a new rigid tripodal oxime ligand

Synthesis and properties of a new rigid tripodal oxime ligand are reported. The ligand is a derivative of phloroglucine with three carboxime arms alternate with hydroxyl groups and three intramolecular OH⋯N hydrogen bonds. Intermolecular OH⋯O hydrogen bonds result in formation of a characteristic three-dimensional network. The structure of the compound is further analyzed and confirmed by NMR, IR and MS-techniques. DFT calculations were employed to accomplish the analysis of both the hydrogen bonding and the conformational state of the ligand under study. Additionally, the study addresses the way the conformational state and metal-replacement influence the tautomeric equilibrium OH⋯N ⇆ O−⋯+HN in the studied moieties.

Effective Photo- and Triboluminescent Europium(III) Coordination Polymers with Rigid Triangular Spacer Ligands.

Luminescent EuIII coordination polymers with rigid triangular spacer ligands are reported. The EuIII coordination polymer, [Eu3 (hfa)9 (tppb)2 ]n (hfa: hexafluoroacetylacetonate, tppb: tris(4-diphenylphosphorylphenyl)benzene), shows high thermo-stability (decomposition temperature=354 °C) and photoluminescence quantum yield (Φ4f-4f =82 %, photosensitized energy transfer efficiency=78 %). The triboluminescence efficiency of EuIII coordination polymer with triangular spacers under laser pulse irradiation (Nd:YAG, λ=1064 nm, pulse width=5 ns, pulse energy=0.1 mJ) is calculated to be 49 %. Characteristic triangular structure, high emission quantum yield, effective photosensitized energy transfer, and remarkable triboluminescence properties of EuIII coordination polymers are demonstrated for the first time.

Heteroleptic Chini-Type Platinum Clusters: Synthesis and Characterization of Bis-Phospine Derivatives of [Pt3n(CO)6n]2- (n = 2-4).

The reactions of [Pt3n(CO)6n]2- (n = 2-4) homoleptic Chini-type clusters with stoichiometric amounts of Ph2PCH2CH2PPh2 (dppe) result in the heteroleptic Chini-type clusters [Pt6(CO)10(dppe)]2-, [Pt9(CO)16(dppe)]2-, and [Pt12(CO)20(dppe)2]2-. Their formation is accompanied by slight amounts of neutral species such as Pt4(CO)4(dppe)2, Pt6(CO)6(dppe)3, and Pt(dppe)2. A similar behavior was observed with the chiral ligand R-Ph2PCH(Me)CH2PPh2 (R-dppp), and two isomers of [Pt9(CO)16(R-dppp)]2- were identified. All the new species were spectroscopically characterized by means of IR and 31P NMR, and their structures were determined by single-crystal X-ray diffraction. The results obtained are compared to those previously reported for monodentate phosphines, that is, PPh3, as well as more rigid bidentate ligands, that is, CH2═C(PPh2)2 (P^P), CH2(PPh2)2 (dppm), and o-C6H4(PPh2)2 (dppb). From a structural point of view, functionalization of anionic platinum Chini clusters preserves their triangular Pt3 units, whereas the overall trigonal prismatic structures present in the homoleptic clusters are readily deformed and transformed upon functionalization. Such transformations may be just local deformations, as found in [Pt9(CO)16(dppe)]2-, [Pt9(CO)16(R-dppp)]2-, [Pt12(CO)22(PPh3)2]2-, and [Pt9(CO)16(PPh3)2]2-; an inversion of the cage from trigonal prismatic to octahedral, as observed in [Pt6(CO)10(dppe)]2- and [Pt6(CO)10(PPh3)2]2-; the reciprocal rotation of two trigonal prismatic units with the loss of a Pt-Pt contact as found in [Pt12(CO)20(dppe)2]2-.

Molecular Simulations Identify Binding Poses and Approximate Affinities of Stapled α-Helical Peptides to MDM2 and MDMX.

Traditionally, computing the binding affinities of proteins to even relatively small and rigid ligands by free-energy methods has been challenging due to large computational costs and significant errors. Here, we apply a new molecular simulation acceleration method called MELD (Modeling by Employing Limited Data) to study the binding of stapled α-helical peptides to the MDM2 and MDMX proteins. We employ free-energy-based molecular dynamics simulations (MELD-MD) to identify binding poses and calculate binding affinities. Even though stapled peptides are larger and more complex than most protein ligands, the MELD-MD simulations can identify relevant binding poses and compute relative binding affinities. MELD-MD appears to be a promising method for computing the binding properties of peptide ligands with proteins.

Pursuit of Record Breaking Energy Barriers: A Study of Magnetic Axiality in Diamide Ligated DyIII Single-Molecule Magnets.

DyIII single-ion magnets (SIMs) with strong axial donors and weak equatorial ligands are attractive model systems with which to harness the maximum magnetic anisotropy of DyIII ions. Utilizing a rigid ferrocene diamide ligand (NNTBS), a DyIII SIM, (NNTBS)DyI(THF)2, 1-Dy (NNTBS = fc(NHSitBuMe2)2, fc = 1,1'-ferrocenediyl), composed of a near linear arrangement of donor atoms, exhibits a large energy barrier to spin reversal (770.8 K) and magnetic blocking (14 K). The effects of the transverse ligands on the magnetic and electronic structure of 1-Dy were investigated through ab initio methods, eliciting significant magnetic axiality, even in the fourth Kramers doublet, thus demonstrating the potential of rigid diamide ligands in the design of new SIMs with defined magnetic axiality.

Nature of metal-dependent assemblies of four coordination polymers based on imidazole substitute isophthalate ligand: Syntheses and crystal structures

Four novel coordination polymers with distinct different structures, {[CdL(H2O)]·0.5H2O}n (1), {[ZnL(H2O)]·H2O}n (2), {[CoL(H2O)2]·2H2O}n (3), and {[NiL(H2O)2]·2H2O}n (4) (L=5-(1-H-imidazole-1-yl)isophthalate) have been synthesized by the reaction of different transition metal cations with a rigid bi-functional ligand L. 1 possesses three-dimensional (3D) network framework, in which Cd(II) center is six coordinated by four L ligands and one aqua molecule. In compound 2, Zn(II) center adopts tetrahedral geometry and coordinated by three L ligands and one aqua molecule. 2 displays a [-AB-(H2O)n-AB-(H2O)n-] fashion 3D supramolecular network, in which A and B are two types of 2D covalent coordination layers. 3 and 4 are isostructural, metal center is six coordinated by three L ligands and two aqua molecules, and the 2D coordination layers construct the 3D supramolecular network with 1D rectangular channels via OH⋯O hydrogen bonds. The structural variation depends on the nature of metal cations. Solid-state luminescent for compounds 1–2 and magnetic properties for compounds 3–4 have been investigated.

Rigid NON-donor pincer ligand complexes of lutetium and lanthanum: synthesis and hydroamination catalysis

A rigid NON-donor pincer ligand was employed for the synthesis of neutral lutetium and anionic lanthanum alkyl complexes; the former is highly active for both intra- and inter-molecular hydroamination.

A series of coordination networks constructed from the rigid ligand 4,4′-ethynylenedibenzoate: topological diversity, entanglement, supramolecular interactions and photophysical properties

Four coordination networks (CNs), i.e., [Co(edb)(H2O)(Py)2], 3; [Cd(edb)(DMSO)2]·0.5(DMSO), 4; [Er2(edb)3(DMSO)2(H2O)2], 5; and [Gd2(edb)3(H2O)4], 6 (edb2− = 4,4′-ethynylenedibenzoate), were synthesized and structurally characterized, and the luminescence properties of CNs 4 and 5 were investigated. In CN 3, the ligand adopts a bridging coordination mode that connects one Co(II) ion to another, resulting in a 1D CN. CNs 4 and 5 contain binuclear centers that are linked to four ligands in the chelating and bridging coordination modes. CN 4 has a 2D → 3D inclined polycatenated structure, whereas CN 5 exhibits a 3D network because the voids created by the long ligand are stabilized by the π–π stacking interactions, thereby avoiding the entanglement of the structure. CN 6 has a paddle-wheel structure with a two-fold interpenetrated rob topology. The photophysical properties of the compound H2edb and CNs 4 and 5 were studied in the solid state. Compound 2 (H2edb) displays strong absorption bands at 325 and 350 nm and emission at 385 nm. Upon complexation with Er(III), the emission was quenched. The emissions of CN 4 were due to the intraligand transitions.

Insilco Modeling of Commonly Occurring Genetic Polymorphism of Human CYP3A4 on the Binding Affinity to UR-144

CYP3A4 accounts for about 30% in the human hepatic metabolism of xenobiotics. The defending mechanism of drug or xenobiotic metabolizing enzymes, particularly CYP superfamily has been found to be altered by both genetic polymorphisms and the environmental factors. The aim of this study was to examine UR-144 binding to CYP3A4 wild type and six different natural variants (I118V, R130Q, R162Q, D174H, T185S and L373F). A rigid ligand was docked by AutoDock Vina to flexible amino acid residues selected from the residues forming the binding pocket. The analysis of the docking results showed there is no difference in the binding affinities between the wild type and the natural variants. However, comparing the absolute binding affinity, the wild type (-12.8kcal/mol) has shown, among all, the lowest binding energy. Thus, this study depicts that the SNPs of CYP3A4 do not have any effects on the binding affinity of UR-144 to the active site.

The photocurrent response in the perovskite device based on coordination polymers: structure, topology, band gap and matched energy levels.

Using a rigid ditopic ligand, 4,5-di(4'-carboxylphenyl)benzene (H2L), three coordination polymers (CPs) formulated as MnL(H2O)2 (1), CdL(H2O) (2) and Mn2L2(DMF)3 (3) have been synthesized and structurally characterized by single-crystal X-ray diffraction. These three CPs display 2D architectures but with different topologies. The experimental data and DFT calculation indicate that CP 2 is a semiconductor, and its CB/VB energy levels match with those of the perovskite CH3NH3PbI3. A FTO/TiO2/CH3NH3PbI3/CP 2 device is fabricated and the CP-based device shows much larger photoresponse under visible light illumination (650 nm > λ > 350 nm, 100 mW cm-2) than the individual CP 2. At 0 V vs. AgCl/Ag, the largest photocurrent density yielded by the CP-based perovskite device is ca. 200 times that of CP 2, which is due to the matched energy levels of all the materials in the device, leading the photogenerated electron-hole pairs to be separated effectively. Meanwhile, the coverage of the insoluble CP on the surface of the perovskite CH3NH3PbI3 can improve the stability of the perovskite against water.

A porous metal-organic framework based on an asymmetric angular diisophthalate for selective adsorption of C2H2 and CO2 over CH4.

A new copper-based metal-organic framework [Cu2L(H2O)2]·5DMF·2H2O (ZJNU-56) has been solvothermally synthesized using a custom-designed asymmetric rigid bent diisophthalate ligand, 5,5'-(1-amine-naphthyl-2,4-diyl) diisophthalic acid (H4L), and structurally determined by single-crystal X-ray diffraction. ZJNU-56 features a three-dimensional (3D) open framework incorporating three different types of metal-organic cages and two distinct types of one-dimensional channels. With a moderate BET surface area of 1655 m2 g-1, optimized pore structure, and functional sites (open copper sites and Lewis basic amine groups) on the cage surface, ZJNU-56 after desolvation exhibits highly selectively adsorptive separation of C2H2 and CO2 over CH4 under ambient conditions. At 298 K, the predicted IAST selectivities are 35.7-72.9 for an equimolar C2H2/CH4 gas mixture and 6.8-7.0 for an equimolar CO2/CH4 gas mixture at pressures varying from 1 to 109 kPa, respectively, which are among the highest reported to date for copper-based MOFs.

Construction of molecular rectangles with titanium-oxo clusters and rigid aromatic carboxylate ligands.

Four rectangular molecular architectures have been successfully constructed using {Ti5O7} clusters as inorganic vertical edges and bridging aromatic carboxylates as horizontal edges. The introduced organic ligands show a strong influence on the light absorption behaviors of the obtained hybrid complexes.

Construction of 3D metal–organic frameworks bearing heteropolyoxometalate units and multi-azole molecules and exploration of their photocatalytic activities

Two novel 3D metal–organic frameworks consisting of rigid ligand modified polyoxomolybdates were obtained and both of them have efficient photocatalytic activities in the degradation of several dye molecules.

A comparative study of magnetization dynamics in dinuclear dysprosium complexes featuring bridging chloride or trifluoromethanesulfonate ligands.

We utilized a rigid ligand platform PyCp22- (PyCp22- = [2,6-(CH2C5H3)2C5H3N]2-) to isolate dinuclear Dy3+ complexes [(PyCp2)Dy-(μ-O2SOCF3)]2 (1) and [(PyCp2)Dy-(μ-Cl)]2 (3) as well as the mononuclear complex (PyCp2)Dy(OSO2CF3)(thf) (2). Compounds 1 and 2 are the first examples of organometallic Dy3+ complexes featuring triflate binding. The isolation of compounds 1 and 3 allows us to comparatively evaluate the effects of the bridging anions on the magnetization dynamics of the dinuclear systems. Our investigations show that although the exchange coupling interactions differ for 1 and 3, the dynamic magnetic properties are dominated by relaxation via the first excited state Kramers doublet of the individual Dy sites. Compounds 1 and 3 exhibit barriers to magnetization reversal (Ueff = 49 cm-1) that can be favorably compared to those of the previously reported examples of [Cp2Dy(μ-Cl)]2 (Ueff = 26 cm-1) and [Cp2Dy(thf)(μ-Cl)]2 (Ueff = 34 cm-1).

A luminescent coordination polymer based on a π-conjugated ligand: Syntheses, structure and luminescent property

A new cadmium coordination polymer [Cd(DPFE)(adip)0.5(NO3)]n (1) has been synthesized hydrothermally from the self-assembly of the Cd2+ ion with a new π-conjugated rigid ligand DPFE and the adipic acid, where DPFE = 2,7-di(pyridin-4-yl)-9H-fluorene and H2adip = adipic acid. The structure of 1 was full characterized by elemental analysis, FT-IR spectroscopy and single crystal X-ray diffraction. Structural analysis reveals compound 1 is a dinuclear Cd(II) based two-dimensional (4,4) layer and two kinds of strong intramolecular π-π stacking interactions exist between pyridyl rings and benzene rings. In addition, the thermogravimetric analysis and solid–state luminescent properties have also been investigated.