X-ray Crystal Structure Analysis Research Articles

Synthesis of an Organometallic Alkyl-Co(III) Complex with Amidoquinoline Directing Groups via C(sp3)–H Activation and Its UV–vis/NMR Spectroscopic, Crystallographic, DFT, and Electrochemical Studies

Abstract The use of earth-abundant and inexpensive Co catalysts for carbon-hydrogen (C–H) bond activation has received increasing attention because of the advantages including air stability. Although directing groups have been effectively introduced in substrates to promote C(sp3)–H activation through chelation assistance, there is a lack of basic information about the isolated alkyl-Co complexes containing directing groups as polydentate ligands. In this study, we report the synthesis and characterization of an alkyl-Co(III) complex 2Co, prepared from a N,N′-bis(8-quinolyl)malonamide derivative, the malonyl fragment of which was disubstituted by two ethyl groups. 2Co was straightforwardly obtained from a Co(II) salt without any use of chemical oxidants but in the presence of air, through selective β-C(sp3)–H activation. The combined NMR spectroscopic and X-ray crystal structural analyses revealed that the malonamide substrate was converted into a pentadentate ligand with an N4C set, acquiring a helical configuration around the Co(III) center. The non-innocent ligand properties of 2Co were unambiguously confirmed by UV–vis spectroscopic, electrochemical, and DFT studies. Thermolysis of 2Co enabled C(sp3)–N reductive elimination in the absence of chemical oxidants. The present study provides important insights into the reactivity of alkyl-Co(III) complexes with a defined coordination geometry around the Co center toward designing elaborate C(sp3)–H functionalization systems.

Synthesis of tropane-based σ1 receptor antagonists with antiallodynic activity

Following the concept of conformational restriction to obtain high affinity σ1 ligands, the piperidine ring of eliprodil was replaced by the bicyclic tropane system and an exocyclic double bond was introduced. The envisaged benzylidenetropanes 9 were prepared by conversion of tropanone 10 into the racemic mixture of (Z)-14 and (E)-14. Reaction of racemate (Z)-14/(E)-14 with enantiomerically pure (R)- or (S)-configured 2-phenyloxirane provided mixtures of diastereomeric β-aminoalcohols (R,Z)-9 and (R,E)-9 as well as (S,Z)-9 and (S,E)-9, which were separated by chiral HPLC, respectively. X-ray crystal structure analysis of (S,Z)-9 allowed the unequivocal assignment of the configuration of all four stereoisomers. In receptor binding studies with radioligands, (R,E)-9 and (S,Z)-9 showed subnanomolar σ1 affinity with eudismic ratios of 8.3 and 40. In both compounds the 4-fluorophenyl moiety is oriented towards (S)-configured C-5 of the tropane system. Both compounds display high selectivity for the σ1 receptor over the σ2 subtype but moderate selectivity over GluN2B NMDA receptors. In vivo, (R,E)-9 (Ki(σ1) = 0.80 nM) showed high antiallodynic activity in the capsaicin assay. The effect of (R,E)-9 could be reversed by pre-administration of the σ1 agonist PRE-084 confirming the σ1 antagonistic activity of (R,E)-9.

Discovery, X-ray Crystallography, and Anti-inflammatory Activity of Bromodomain-containing Protein 4 (BRD4) BD1 Inhibitors Targeting a Distinct New Binding Site.

Bromodomain-containing protein 4 (BRD4) is an emerging epigenetic drug target for intractable inflammatory disorders. The lack of highly selective inhibitors among BRD4 family members has stalled the collective understanding of this critical system and the progress toward clinical development of effective therapeutics. Here we report the discovery of a potent BRD4 bromodomain 1 (BD1)-selective inhibitor ZL0590 (52) targeting a unique, previously unreported binding site, while exhibiting significant anti-inflammatory activities in vitro and in vivo. The X-ray crystal structural analysis of ZL0590 in complex with human BRD4 BD1 and the associated mutagenesis study illustrate a first-in-class nonacetylated lysine (KAc) binding site located at the helix αB and αC interface that contains important BRD4 residues (e.g., Glu151) not commonly shared among other family members and is spatially distinct from the classic KAc recognition pocket. This new finding facilitates further elucidation of the complex biology underpinning bromodomain specificity among BRD4 and its protein-protein interaction partners.

Substitution of Hyp (Hyp = Si(SiMe3)3) at metalloid [Ge9(Hyp)3]- clusters using phosphine stabilized Au(I)Cl.

We present two new intermetalloid cluster compounds [(nBu3P)AuGe9(Hyp)2Au(PnBu3)]2 (1) and [Au(iPr2POC6H4OPiPr2)AuGe9(Hyp)2]2 (2) which are obtained from the reaction of KGe9(Hyp)3 (Hyp = Si(SiMe3)3) with the respective Au(I) phosphine precursors. The products are characterized via X-ray crystal structure analysis and the reaction course is analysed via NMR spectroscopy. We also show that in the resulting compound 1 the hypersilyl substituents can be reintroduced via the reaction with Hyp-Cl to obtain nBu3PAuGe9(Hyp)3.

Effect of chalcogen bonding interactions on molecular structures; theoretical and crystallographic studies on two palladium(ii) acetate complexes

New palladium complexes, [Pd(L)(OAc))], have been synthesized. The complexes and their ligand have been characterized by X-ray crystal structure analysis. Interestingly, the molecular structures of the two complexes are stabilized by S⋯O chalcogen bonds.

Nucleophilic ability of 5-aminopyrazoles in the multicomponent synthesis of pyrazolodihydropyridines and pyrazolodihydropyrimidines

The nucleophilic ability of substituted 5-aminopyrazoles and the type of dicarbonyl component were investigated to synthesise various pyrazolodihydropyridines and pyrazolodihydropyrimidines. In this multicomponent reaction, two possible reaction mechanisms are proposed to elucidate the importance of the nucleophilic positions in the 5-aminopyrazole molecule leading to the different cyclocondensation products. The extent of the nucleophilicity of the C4-position (β-position of the enamine moiety), the lone pairs of the N1-atom and the NH2 group in the pyrazole molecule affect the reaction time and type of product formed. The acidity of the CH2 moiety of the β-dicarbonyl compound may affect the type of product formed. 1H and 13C NMR data and the X-ray crystal structure analysis support the experimental work and the formed product type.

Selective and rapid water transportation across a self-assembled peptide-diol channel via the formation of a dual water array.

Achieving superfast water transport by using synthetically designed molecular artifacts, which exclude salts and protons, is a challenging task in separation science today, as it requires the concomitant presence of a proper water-binding site and necessary selectivity filter for transporting water. Here, we demonstrate the water channel behavior of two configurationally different peptide diol isomers that mimic the natural water channel system, i.e., aquaporins. The solid-state morphology studies showed the formation of a self-assembled aggregated structure, and X-ray crystal structure analysis confirmed the formation of a nanotubular assembly that comprises two distinct water channels. The water permeabilities of all six compounds were evaluated and are found to transport water by excluding salts and protons with a water permeability rate of 5.05 × 108 water molecules per s per channel, which is around one order of magnitude less than the water permeability rate of aquaporins. MD simulation studies showed that the system forms a stable water channel inside the bilayer membrane under ambient conditions, with a 2 × 8 layered assembly, and efficiently transports water molecules by forming two distinct water arrays within the channel.

Hierarchical supramolecular co-assembly formation employing multi-component light-harvesting charge transfer interactions giving rise to long-wavelength emitting luminescent microspheres.

Charge transfer (CT) interaction induced formation of a hierarchical supramolecular assembly has attracted attention due to its wide diversity of structural and functional characteristics. In the present work, we report the generation of green luminescent microspheres from the charge transfer interaction induced co-assembly of a bis-naphthyl dipicolinic amide (DPA) derivative with tetracyanobenzene (TCNB) for the first time. The properties of these self-assemblies were studied both in solution and the solid-state using spectroscopic and a variety of microscopy techniques. The X-ray crystal structure analysis showed a mixed stack arrangement of DPA and TCNB. The molecular orbital and energy level calculations confirm the charge transfer complex formation between DPA and TCNB. Furthermore, energy transfer was observed from the green luminescent CT complex to a red-emitting dye, pyronin Y, in the microsphere matrix, leading to the formation of a light-harvesting tri-component self-assembly.

An investigation into the impact of introduced thiocyanate anions on the trinuclear Co(II) salamo-based complex

The reaction of Co(OAc)2·4H2O with multisite coordinated salamo-based ligand H2L containing six coordinating sites in presence of co-ligand NCS- anions afforded successfully a trinuclear Co(II) complex [Co3(L)2(NCS)2]. The trinuclear Co(II) complex has been characterized by elemental analyses, UV-visible, Fourier transform infrared spectroscopic methods and DFT calculation. In addition, the structure of the Co(II) complex has been confirmed by single crystal X-ray crystallography. X-ray crystal structure analysis of the Co(II) complex revealed that the Co(II) complex consists of three Co(II) atoms coordinated by two fully deprotonated ligand (L)2- units and co-ligand NCS- anions. The close surveillance of the crystal structure of the Co(II) complex discloses some notable non-covalent interactions like H-bonding, C-H···π and π···π. The luminescent property of the Co(II) complex has been studied in methanol solution. Apart from, as a complementary revelation, intermolecular interactions with respect to percentages of hydrogen bondings in the X-ray crystal structure of the trinuclear Co(II) complex was quantified by analyses of Hirshfeld surfaces and fingerprint plots.

Synthesis and structure of a pyridine-stabilized silanone molybdenum complex and its reactions with PMe3 and acetone.

Silanones (OSiR2) are highly reactive species that readily convert to oligomeric siloxane (O-SiR2)n. The coordination of silanones to transition metal fragments to afford silanone-coordinated complexes is a reliable silanone stabilization method. Herein, a pyridine-stabilized silanone molybdenum complex Cp*(OC)2Mo{OSiMes2(py)}(SiMe3) (2b, Cp*: η5-C5Me5, Mes: 2,4,6-Me3C6H2, and py: pyridine) was synthesized by reacting the silyl(silylene) complex Cp*(OC)2Mo(SiMes2)(SiMe3) (4b) with pyridine-N-oxide in pyridine. X-ray crystal structure analysis revealed that the geometry of complex 2b is similar to those of the previously synthesized DMAP-stabilized analogue Cp*(OC)2Mo{OSiMes2(DMAP)}(SiMe3) (2a, DMAP: 4-(dimethylamino)pyridine). The SiO and Mo-O bond distances in 2b are similar to those observed in 2a, but the N-Si coordination bond of 2b is slightly longer (approximately 0.05 Å) than that of 2a, indicating weaker pyridine coordination than that of DMAP. The reaction of 2a with excess PMe3 in C6D6 at room temperature for 28 h afforded Cp*(OC)2Mo(PMe3)(SiMe3) (5c) in a 43% NMR yield. In contrast, reacting 2b with excess PMe3 in C6D6 at room temperature for 9 h afforded 5c and the five-membered metallacyclic carbene complex Cp*(OC)Mo(C(SiMe3)OSiMes2O)(PMe3) (6) in 10% and 41% NMR yields, respectively. The reactions of pyridine-stabilized silanone complexes Cp*(OC)2M(OSiMes2(py))(SiMe3) (M = Mo (2b) and W (1b)) with acetone proceeded via pyridine elimination, coordination of acetone to the Si center in the silanone ligand, and elimination of HSiMe3 to give Cp*(OC)2M{OSiMes2OC(Me)CH2} (M = Mo (8) and W (9)) in high yields.

Zn/Al-centered tetrahedral framework oxide Ba4Zn2Al2O9

Single crystals of Ba4Zn2Al2O9 were obtained by heating a mixture of BaCO3, ZnO, and Al2O3 at 1413 ​K in a dry air atmosphere. X-ray crystal structure analysis revealed that the compound crystalizes in a monoclinic cell (a ​= ​6.9444(2) Å, b ​= ​5.91650(10) Å, c ​= ​13.5842(3) Å, β ​= ​103.955(1)°) with the space group P21/n. The crystal structure can be characterized as a substitution of Zn/AlO4 tetrahedra for B-cation-centered O octahedra of a perovskite-type structure (ABO3). The vacant spaces surrounded by planes of the tetrahedra with eight- and ten-fold coordinations of O atoms are occupied by Ba atoms. The melting temperature (1444 ​K), electrical conductivity (1.5 ​× ​10–6 ​S ​cm–1 at 1073 ​K), relative permittivity (24 ​at 298 ​K and 1 ​MHz), and linear thermal expansion coefficient (9.72 ​× ​10–6 ​K–1 ​at 298–873 ​K) of a polycrystalline bulk sample were measured.

Ruthenium Complexes Bearing Axially Chiral Bipyridyls: The Mismatched Diastereomer Showed Red Circularly Polarized Phosphorescence.

RutheniumII complexes bearing three axially chiral bipyridyl ligands were synthesized as a new family of chiral complex dyes, and Δ-(S)- and Λ-(S)-diastereomers were obtained. The X-ray crystal structure analyses, spectroscopy, and DFT calculations suggested that all the bipyridyls maintained chirality in both the ground and excited states, and the Δ-(S)- and Λ-(S)-isomers are the matched (more relaxed) and mismatched (more constrained) pairs, respectively. The mismatched Λ-(S)-isomer exhibited red circularly polarized phosphorescence (CPP) both in solution and in the solid state. The solution state CPP is the most intense of ruthenium complexes, while the solid state CPP is the first example of them. It is supposed that, for the Λ-(S)-isomer, the six cumulative CH/π interactions suppress further distortion in the T1 state.

Synthesis, Structures, and Properties of Triskelion-Shaped Fluorophores Bearing Coumarins with Nitrogen-Containing Donor Groups

Abstract Triskelion-shaped π-fluorophores bearing coumarins with nitrogen-containing donor groups (1a, 1b, and 1c) were successfully synthesized via intramolecular Ullmann coupling. X-ray crystal structure analysis revealed that 1a and 1b adopt curved propeller-shaped structures similar to that of parent compound 1-H. A theoretical study suggested that compounds 1a–1c possess two different molecular surfaces, as do Janus-type molecules. The emission spectra of 1a–1c in toluene showed broad emission bands at 570, 599, and 600 nm with a large Stokes shift at 4430–5930 cm−1. Although compounds 1a and 1b exhibited more intense fluorescence emission compared with that of parent compound, the emission intensity decreases in high-polarity solvents due to broken symmetry resulting from the twisting of the donor groups. Conversely, compound 1c showed weak emission in all tested solvents. These curved and triskelion-shaped fluorophores were found to form nanoaggregates in THF/H2O mixtures and demonstrated outstanding aggregation-induced emission enhancement (AIEE) properties.

Influence of different solvents on structures and electronic properties of new Fe2S2 complexes containing bis(2-diphenylphosphinophenyl)ether

In order to observe solvent effects on structures and properties of [FeFe]-hydrogenase, two Fe2S2 complexes, [Fe2(μ-pdt)(CO)4(DPEphos)] • CH2Cl2 (1) and [Fe2(μ-pdt)(CO)4 (DPEphos)] •[Fe2 (μ-pdt)(CO)4 (DPEphos)] (2) (DPEphos =bis(2-diphenyl phosphinophenyl)ether), have been prepared and characterized by IR, 1H NMR, 31P NMR, TG and X-ray crystal structure analysis. Structural analysis shows that the [Fe2(μ-pdt)(CO)4(DPEphos)] unit in 1 and 2 includes a butterfly Fe2S2 core, in which each iron atom is five-coordinated with a pseudo-square pyramidal geometry, and the change of the crystallization solvent from CH2Cl2 to toluene leads to the variation of crystallographic system, space group and the weak interactions. DFT studies indicate that the component of the HOMOs and LUMOs at different solvents for [Fe2(μ-pdt)(CO)4(DPEphos)] are nearly identical, which are primarily composed of CO, μ-pdt, Fe atoms and -Ph2P groups, coinciding with the change of DOS and PDOS at different solvents. Meanwhile, the HOMO and LUMO energies, HOMO → LUMO energy gap and Mülliken atomic charges at methanol, ethanol, dichloromethane and nitrobenzene are only a little change, which have much more changes than the relevant values at solvent-free model. All these show that the solvent has an important influence on structures and electronic properties of Fe2S2 complexes.

Structural characterization, DFT studies and luminescent properties of dinuclear copper(I)-diimine complexes with the S-shape configurations

Three dinuclear Cu(I) complexes, [Cu2(pnd)(PPh3)4](BF4)2(1), [Cu2(pnd)(dppp)2] (BF4)2(2), and [Cu2(pnd)(DPEphos)2](BF4)2(3) (PPh3 = triphenylphosphine, dppp = 1, 3-bis (diphenylphosphino)propane, DPEphos = bis(2-diphenylphosphinophenyl)ether, pnd = N, N’-bis (pyridin-2-ylmethylene)naphthyl-1, 5-diimine), have been prepared and characterized by IR, 1H NMR, 31P NMR, 13C NMR, XRD, elemental analysis and X-ray crystal structure analysis. The structural analysis reveals that the flexible pnd in 1–3 acts in a trans bridging coordination mode to connect two Cu+ ions, forming a S-shape conformation, while each of Cu (I) ion is four-coordinate N2P2, adopting a distorted-tetrahedral geometry. DFT calculations show that the HOMOs of complexes 1–3 are primarily located on the copper d-orbital and the phosphine ligand, together with a specific contribution of pnd, while LUMOs are mostly composed of pnd with admixed Cu(I) d-orbital character. Corresponding calculations of atomic charges indicate that the charge of the copper atom in complexes 1–3 is below + 1, while the total charges of the coordinated atoms are 0.743–0.786. Moreover, the solid-state emission spectra of complexes 1–3 show the existence of broad emission bands at 350–550 nm.

Synthesis and Conformational Characteristics of Calix[4]arene Oligomers

Abstract Lower- and/or upper-rim functionalization of calix[4]arene realized a variety of calix[4]arene systems. Compared to these monomeric calix[4]arenes, covalently linked calix[4]arene oligomers have not been studied well. Calix[4]arene oligomers can be utilized as building blocks of supramolecular complexes as well as for the synthesis of calix[4]arene polymers. This background motivated us to develop synthetic procedures for calix[4]arene oligomers and to conduct conformational analysis of these oligomers. We produce oligomers ranging from the monomer to the pentamer. The coupling of the pentamer with 2,3-dibenzyloxy-1,4-benzenedicarboxylic acid can access a decamer and oligomers. NMR measurements, X-ray crystal structure analysis, and computational studies demonstrate that calix[4]arene oligomers can regulate their length by changing the conformations of the calix[4]arene cores.

Hirshfeld surfaces analysis and DFT study of the structure and IR spectrum of N-ethyl-2-amino-1-(4-chlorophenyl)propan-1-one (4-CEC) hydrochloride

This paper represents a Hirshfeld surfaces analysis of crystalline 4-chloroethylcathinone (4-CEC) hydrochloride and a quantum chemical study of the IR spectrum of 4-CEC dimer, which models the crystalline structure of 4-CEC within the framework of density functional theory (DFT) with B3LYP functional and 6-31G(d,p) basis set. The Hirshfeld surfaces analysis of 4-CEC X-ray crystal structure reveals that NH∙∙∙Cl, CH∙∙∙Cl and π∙∙∙π interactions play a major role in the cooperative way of crystal architecture securing and approves the formation of the NH2+–Cl– salt fragment in the 4-CEC crystal. The same structural trends are supported by the Bader’s QTAIM analysis of density gradients and critical points. The DFT calculated infrared spectrum of the investigated psychotropic substance contains absorption features, which correspond to the frequency and relative intensity of the experimental IR bands of the 4-CEC standard sample. All IR bands being assigned and interpreted in the experimental spectrum of the 4-CEC standard crystal sample represent an important aspect of analytical chemistry in the forensic problems. It is shown that the presence of the ionized form of the 4-CEC compound, which contains the NH2+Cl– fragment, is a key condition for the correct reproduction of the IR spectrum when calculating the dimer structure as a model of a crystalline sample. The unravel of the complicated nature of the IR bands associated with vibration of the NH2+Cl– fragment is an important achievement of the present study.

A new halogen bonding 1,2-iodo-triazolium-triazole benzene motif for anion recognition

The synthesis of a series of halogen bonding (XB) acyclic anion receptors based on a novel 1,2-iodo-triazolium-triazole benzene motif is reported. A combination of one- and two-dimensional 1H and 19F NMR spectroscopic techniques elucidate key conformational effects associated with the incorporation of ortho-substituted iodo-triazole based XB donors. 1H NMR anion titration experiments highlight the anion recognition potency of a mono-cationic XB iodo-triazolium-triazole benzene receptor, remarkably forming stronger halide complexes in comparison to a dicationic hydrogen bonding (HB) bis-proto-triazolium receptor analogue. X-ray crystal structure analysis provide insights into halide binding induced conformational changes and coordination modes, revealing the unique electronic and steric consequences associated with multidentate XB donor arrays.

Noncovalent Interactions at Lanthanide Complexes.

Lanthanide complexes have attracted a widespread attention due to their structural diversity, as well as multifunctional and tunable properties. The development of lanthanide based functional materials has often relied on the design of the secondary coordination sphere of the corresponding lanthanide complexes. For instance, usually simple lanthanide salts (solvento complexes) do not catalyze effectively organic reactions or provide low yield of the expected product, whereas the presence of a suitable organic ligand with a noncovalent bond donor or acceptor centre (secondary coordination sphere) modifies the symmetry around the metal centre in lanthanide complexes which then successfully can act as catalysts in both homogenous and heterogenous catalysis. In this minireview, we discuss several relevant examples, based on X-ray crystal structure analyses, in which the hydrogen, halogen, chalcogen, pnictogen, tetrel and rare-earth bonds, as well as cation-π, anion-π, lone pair-π, π-π and pancake interactions, are used as a synthon in the decoration of the secondary coordination sphere of lanthanide complexes.

Abstract P362: Gata4 Dimerization May Be A Target For Heart Failure Therapy

Introduction: Cardiac hypertrophy is regulated by activation of GATA4. Although GATA4 post-translational modification such as acetylation by p300 is well examined, the details of the activation mechanism of GATA4 are still unclear. The purpose of this study is to investigate whether GATA4 dimerization involved in transcriptional activation and cardiomyocyte hypertrophic responses. Methods and Results: A GST pull-down assay using GST fusion GATA4 full-length and deletion mutants demonstrated that GATA4 308-326, including the acetylation site, was required for the dimerization of GATA4. A DNA pull down assay showed that the C-zinc finger motif (256-295) and the acetylation site were required for the DNA binding capacity of GATA4. IP-WB using nuclear extract from HEK293T cells expressing FLAG- or HA-tagged GATA4 showed that co-expression of p300 increased the formation of the homo-dimer as well as acetylation of GATA4. The GATA4 homo-dimer was disrupted by both acetyl-deficient GATA4 and HAT-deficient p300. This result indicates that acetylation of GATA4 is important for dimerization of GATA4. Overexpression of the deletion mutant containing a GATA4 308-326 (G4D) prevented p300-induced GATA4 dimerization but not the p300 binding nor acetylation of GATA4. ChIP assay and DNA pulldown assay showed that G4D did not inhibit the p300-induced DNA binding of GATA4. In cardiomyocytes, the G4D inhibited phenylephrine-induced ANF and ET-1 promoter activities and cardiomyocyte hypertrophy. To perform the X-ray crystal structure analysis, recombinant GATA4 fragment including GATA4 308-326 was highly purified. The X-ray diffraction data of obtained crystals was collected. Resolution of the crystal was 3.1Å, which was insufficient for phase determine. To obtain a high-quality crystal, GATA4 fragment was crystallized in international space station, in collaboration with JAXA. Resolution of the crystal was 3.16Å, which was similar to the best data before obtained. Conclusions: These results suggest that GATA4 dimerization may play an important role in hypertrophy-response gene transcription. It is expected to elucidate the GATA4 dimerization mechanism and targeted this dimerization will lead to the development of a noble heart failure therapy.