Phenoxythiazoline (FTz)-Cobalt(II) Precatalysts Enable C(sp2 )-C(sp3 ) Bond-Formation for Key Intermediates in the Synthesis of Toll-like Receptor 7/8 Antagonists.

Evaluation of the relative rates of the cobalt-catalyzed C(sp2 )-C(sp3 ) Suzuki-Miyaura cross-coupling between the neopentylglycol ester of 4-fluorophenylboronic acid and N-Boc-4-bromopiperidine established that smaller N-alkyl substituents on the phenoxyimine (FI) supporting ligand accelerated the overall rate of the reaction. This trend inspired the design of optimal cobalt catalysts with phenoxyoxazoline (FOx) and phenoxythiazoline (FTz) ligands. An air-stable cobalt(II) precatalyst, (FTz)CoBr(py)3 was synthesized and applied to the cross-coupling of an indole-5-boronic ester nucleophile with a piperidine-4-bromide electrophile that is relevant to the synthesis of reported toll-like receptor (TLR) 7/8 antagonist molecules including afimetoran. Addition of excess KOMe⋅B(Oi Pr)3 improved catalyst lifetime due to attenuation of alkoxide basicity that otherwise resulted in demetallation of the FI chelate. A first-order dependence on the cobalt precatalyst and a saturation regime in nucleophile were observed, supporting turnover-limiting transmetalation and the origin of the observed trends in N-imine substitution.

Polydentate N,O-Ligands Possessing Unsymmetrical Urea Fragments Attached to a p-Cresol Scaffold.

In this study, three series of polydentate N,O-ligands possessing unsymmetrical urea fragments attached to a p-cresol scaffold are obtained, namely mono- and bi-substituted open-chain aromatics, synthesised using a common experiment, as well as fused aryloxazinones. Separate protocols for the preparation of each series are developed. It is found that in the case of open-chain compounds, the reaction output is strongly dependent on both bis-amine and carbamoyl chloride substituents, while oxazinones can be effectively obtained via a common protocol. The products are characterized via 1D and 2D NMR spectra in solution and using single-crystal XRD. A preliminary study on the coordination abilities of the products performed via ITC shows that there are no substantial interactions in the pH range of 5.0-8.5 in general.

Radionuclide Cisternography with [64Cu]Cu-DOTA.

Radionuclide cisternography (RNC) is a method for conducting imaging of the cerebrospinal system and can be used to identify cerebrospinal fluid leaks. So far, RNC has commonly employed radiopharmaceutical agents suitable only for single-photon emission tomography techniques, which are thus lacking in terms of image resolution and can potentially lead to false-negative results. Therefore, [64Cu]Cu-DOTA was investigated as an alternative radiopharmaceutical for RNC, employing positron emission tomography (PET) instead of single-photon emission tomography. A formulation of [64Cu]Cu-DOTA was produced according to the guidelines for good manufacturing practice. The product met the requirements of agents suitable for intrathecal application. [64Cu]Cu-DOTA was administered to a patient and compared to the approved scintigraphic RNC agent, [111In]In-DTPA. While no cerebrospinal fluid leak was detected with [111In]In-DTPA, [64Cu]Cu-DOTA RNC exhibited a posterolateral leak between the vertebral bodies C1 and C2. Thus, in this patient, PET RNC with [64Cu]Cu-DOTA was superior to RNC with [111In]In-DTPA. Since radiopharmaceuticals have a very good safety profile regarding the occurrence of adverse events, PET RNC with [64Cu]Cu-DOTA may become an attractive alternative to scintigraphic methods, and also to computed tomography or magnetic resonance imaging, which often require contrast agents, causing adverse events to occur much more frequently.

Chiral-at-Metal Racemization Unraveled for MX2 (a-chel)2 by means of a Computational Analysis of MoO2 (acnac)2.

Octahedral chiral-at-metal complexes MX2 (a-chel)2 (a-chel=asymmetric chelate) can rearrange their ligands by four mechanisms known as the Bailar (B), Ray-Dutt (RD), Conte-Hippler (CH), and Dhimba-Muller-Lammertsma (DML) twists. Racemization involves their interconnections, which were computed for MoO2 (acnac)2 (acnac=ß-ketoiminate) using density functional theory at ωB97x-D with the 6-31G(d,p) and 6-311G(2d,p) basis sets and LANL2DZ for molybdenum. Racemizing the cis(NN) isomer, being the global energy minimum with trans oriented imine groups, is a three step process (DML-CH-DML) that requires 17.4 kcal/mol, while all three cis isomers (cis(NN), cis(NO), and cis(OO)) interconvert at ≤17.9 kcal/mol. The B and RD twists are energetically not competitive and neither are the trans isomers. The interconnection of all enantiomeric minima and transition structures is summarized in a graph that also visualizes valley ridge inflection points for two of the three CH twists. Geometrical features of the minima and twists are given. Lastly, the influence of N-substitution on the favored racemization pathway is evaluated. The present comprehensive study serves as a template for designing chiral-at-metal MX2 (a-chel)2 catalysts that may retain their chiral integrity.

Exploring the in vitro anticancer activities of Re(I) picolinic acid and its fluorinated complex derivatives on lung cancer cells: a structural study.

Fifteen rhenium(I) tricarbonyl complexes of the form fac-[Re(N,O')(CO)3(X)], where N,O'-bidentate ligand = 2-picolinic acid (Pico); 3,5-difluoropyridine-2-carboxylic acid (Dfpc); 3-trifluoromethyl-pyridine-2-carboxylic acid (Tfpc) and X = H2O; pyrazole (Pz); pyridine (Py); imidazole (Im); and methanol (CH3OH) were synthesized using the '2 + 1' mixed ligand approach with an average yield of 84%. The complexes were characterized using the following spectroscopic techniques: IR, 1H and 13C NMR, UV/Vis, and single-crystal X-ray diffraction. The effect of the fluorine atoms on the backbone of the N,O'-bidentate ligand was investigated and a trend was noticed in the carbonyl stretching frequencies: with Pico < Tfpc < Dfpc. The in vitro biological screening on Vero (healthy mammalian), HeLa (cervical carcinoma) and A549 (lung cancer) cells revealed one toxic complex, fac-[Re(Pico)(CO)3(H2O)], with respective LC50 values of 9.0 ± 0.9, 15.8 ± 4.9 (SI = 0.570) and 20.9 ± 0.8 (SI = 0.430) µg/mL. As a result, it can be used as a positive control drug of toxicity.

Automated GMP Production and Preclinical Evaluation of [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA.

[68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model. After low radiolabeling yields were attributed to precursor instability at high temperatures, an optimized radiolabeling procedure was established. Quality controls were in accordance with Ph. Eur. requirements and gave compliant results, although the method for the determination of the 68Ga colloid is partially inhibited due to the presence of a radioactive by-product. The determination of logP revealed [68Ga]Ga-TEoS-DAZA (ethoxy bearing) to be more lipophilic than [68Ga]Ga-TMoS-DAZA (methoxy bearing). Accordingly, biodistribution studies in an in ovo model showed a higher liver uptake for [68Ga]Ga-TEoS-DAZA. In dynamic in ovo PET imaging, rapid tracer accumulation in the liver was observed. Similarly, the activity in the intestines rose steadily within the first hour p.i., indicating biliary excretion. As [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA can be prepared according to GMP guidelines, transition into the early clinical phase is now possible.

Copper(II) Compounds of 4-Nitrobenzohydrazide with Different Anions (ClO4 - , NO3 - and Br- ): Synthesis, Characterization, DFT Calculations, DNA Interactions and Cytotoxic Properties.

Copper complexes containing 4-nitrobenzohydrazide (4-NH), [Cu(4-NH)2 (ClO4 )2 ] (1), [Cu(4-NH)2 (NO3 )2 ] (2) and [Cu(4-NH)2 Br2 ] (3), were synthesized and characterized by various spectroscopy. DFT calculations have revealed a distorted octahedral for 1, 2 and 3. DNA interactions of 1-3 toward calf-thymus DNA were investigated by absorption titration, viscosity, fluorescence spectroscopy and gel electrophoresis. All complexes bind to DNA via intercalation mode. The Kb values have shown the binding ability in the order of 3>2>1. The in vitro cytotoxicity of 1-3 was tested against two human cancer cells (HeLa and MCF-7) and normal Vero cells by MTT assay. All complexes show anticancer ability upon increasing time, but the ligand is inactive. Complex 3 with the Br- anion gives the lowest IC50 values of 19.26±2.43 µg/mL toward MCF-7. Moreover, all complexes were not arrested at any cell cycle phases. However, the sub-G1 populations were enhanced upon increasing the complex concentration. Therefore, they may induce apoptotic cell death for both cancer cells. The antibacterial activity of 1-3 was tested against E. coli, Salmonella and Campylobacter. Complex 3 gives the best activity toward Campylobacter (0.156×103  µg/mL).

Tunable Synchronicity of Molecular Valence Tautomerism with Macroscopic Solid-Liquid Transition by Molecular Lattice Engineering.

The combination of a cobalt-dioxolene core that exhibits valence tautomerism (VT) with pyridine-3,5-dicarboxylic acid functionalized with chains bearing two, four, or six oxyethylene units led to new complexes ConEGEspy (n = 2, 4, and 6). These complexes commonly form violet crystals of the low-spin (ls)-[CoIII (nEGEspy)2 (3,6-DTBSQ)(3,6-DTBCat)] (ls-[CoIII ], 3,6-DTBSQ = 3,6-di-tert-butyl semiquinonato, 3,6-DTBCat = 3,6-di-tert-butyl catecholato). Interestingly, violet crystals of Co2EGEspy in the ls-[CoIII ] transitioned into a green liquid, accompanied by an almost complete VT shift (94 %) to the high-spin (hs)-[CoII (nEGEspy)2 (3,6-DTBSQ)2 ] (hs-[CoII ]) upon melting. In contrast, violet crystals of Co4EGEspy and Co6EGEspy in the ls-[CoIII ] exhibited partial VT (33 %) and only a 9.3 % VT shift after melting, respectively. These data demonstrate the tunability of the synchronicity of the molecular VT and macroscopic solid-liquid transitions by optimizing the tethered chains, thus establishing a new strategy for coupling bistable molecules with the macroscopic world.

Neutral Unsymmetrical Coordinated Cyclophane Polymerization Catalysts.

Cyclophane structures can control steric pressure in the otherwise open spaces of square-planar d8 -metal catalysts. This elegant concept was so far limited to symmetrical coordinated metals. We report how a cyclophane motif can be generated in ligands that chelate via two different donors. An ancillary second imine in the versatile κ2 -N,O-salicylaldiminato catalyst type enables ring closure via olefin metathesis and selective double bond hydrogenation to yield a 30-membered ring efficiently. Experimental and theoretical analyses show the ancillary imine is directed away from the active site and inert for catalysis. In ethylene polymerization the cyclophane catalyst is more active and temperature stable vs. an open structure reference, notably also in polar solvents. Increased molecular weights and decreased degrees of branching can be traced to an increased energy of sterically demanding transition states by the encircling cyclophane while chain propagation remains highly efficient.

Short Radiative Lifetime and Non-Triplet Sensitization in Near-Infrared-Luminescent Yb(III) Complex with Tripodal Schiff Base.

We prepared Ln(III) (Ln=Eu, Gd, and Yb) complexes with a tripodal Schiff base, tris[2-(5-methylsalicylideneimino)ethyl]amine (H3 L) and studied their photophysical properties. Upon ligand excitation, YbL showed Yb(III)-centered luminescence in the near-infrared region. While the overall quantum yield (0.60(1)%) of YbL in acetonitrile was moderate among the reported values for Yb(III) complexes, its radiative lifetime (0.33(2) ms) was significantly shorter than those reported previously. We propose that the ligand-to-metal charge-transfer (LMCT) state mediated the sensitization in YbL. The emission and excitation spectra of EuL indicated the participation of the LMCT state in the sensitization. The radiative lifetime (0.84(7) ms) for EuL in the solid state was rather short compared to those of reported Eu(III) complexes. Our results show that the Yb(III) complex with the Schiff base ligand has two features: the short radiative lifetime and the non-triplet sensitization path.

FeIII and FeII Phosphasalen Complexes: Synthesis, Characterization, and Catalytic Application for 2-Naphthol Oxidative Coupling.

We report on the synthesis and characterization of three iron(III) phosphasalen complexes, [FeIII (Psalen)(X)] differing in the nature of the counter-anion/exogenous ligand (X- =Cl- , NO3 - , OTf- ), as well as the neutral iron(II) analogue, [FeII (Psalen)]. Phosphasalen (Psalen) differs from salen by the presence of iminophosphorane (P=N) functions in place of the imines. All the complexes were characterized by single-crystal X-ray diffraction, UV/Vis, EPR, and cyclic voltammetry. The [FeII (Psalen)] complex was shown to remain tetracoordinated even in coordinating solvent but surprisingly exhibits a magnetic moment in line with a FeII high-spin ground state. For the FeIII complexes, the higher lability of triflate anion compared to nitrate was demonstrated. As they exhibit lower reduction potentials compared to their salen analogues, these complexes were tested for the coupling of 2-naphthol using O2 from air as oxidant. In order to shed light on this reaction, the interaction between 2-naphthol and the FeIII (Psalen) complexes was studied by cyclic voltammetry as well as UV/Vis spectroscopy.

Crystal structure, characterization and Hirshfeld analysis of bis-{(E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naphthalen-2-olato}copper(II) dimethyl sulfoxide monosolvate.

In the title compound, [Cu(C16H8Br3N2O)2]·C2H6OS, the CuII atom is tetra-coordinated in a square-planar coordination, being surrounded by two N atoms and two O atoms from two N,O-bidentate (E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naphthalen-2-olate ligands. The two N atoms and two O atoms around the metal center are trans to each other, with an O-Cu-O bond angle of 177.90 (16)° and a N-Cu-N bond angle of 177.8 (2)°. The average distances between the CuII atom and the coordinated O and N atoms are 1.892 (4) and 1.976 (4) Å, respectively. In the crystal, complexes are linked by C-H⋯O hydrogen bonds and by π-π inter-actions involving adjacent naphthalene ring systems [centroid-centroid distance = 3.679 (4) Å]. The disordered DMSO mol-ecules inter-act weakly with the complex mol-ecules, being positioned in the voids left by the packing arrangement of the square-planar complexes. The DMSO solvent mol-ecule is disordered over two positions with occupancies of 0.70 and 0.30.

Dinuclear ZnII Complexes Exhibiting Thermally Activated Delayed Fluorescence and Luminescence Polymorphism.

ZnII complexes exhibiting strong emission in the solid state remain scarce, and most of them exhibit only prompt fluorescence. Herein the synthesis, structures, and photoluminescence properties of two ZnII complexes containing new donor-acceptor ligands is reported. The new ZnII complexes have dinuclear structures in which each metal ion adopts a distorted square-pyramidal geometry. The ZnII complexes show strong emission in the solid state with quantum yields up to 50 %. Variable-temperature transient photoluminescence studies revealed an emission mechanism involving prompt and thermally activated delayed fluorescence (TADF). DFT calculations showed well-separated HOMO and LUMO in the ground state and small excited singlet-triplet energy splitting, accounting for the TADF. The complexes also exhibit different emission colors in the as-synthesized powder state and in single crystals, that is, they exhibit luminescence polymorphism. The single-crystal emission is responsive to mechanical grinding and was characterized by powder XRD.

In Situ Metal-Assisted Ligand Modification Induces Mn4 Cluster-to-Cluster Transformation: A Crystallography, Mass Spectrometry, and DFT Study.

Dehydration of (S,S)-1,2-bis(1H-benzo[d]imidazol-2-yl)ethane-1,2-diol (H4 L) to (Z)-1,2-bis(1H-benzo[d]imidazol-2-yl)ethenol) (H3 L') was found to be metal-assisted, occurs under solvothermal conditions (H2 O/CH3 OH), and leads to [MnII 4 (H3 L)4 Cl2 ]Cl2 ⋅5 H2 O⋅5 CH3 OH (Mn4 L4 ) and [MnII 4 (H2 L')6 (µ3 -OH)]Cl⋅4 CH3 OH⋅H2 O (Mn4 L'6 ), respectively. Their structures were determined by single-crystal XRD. Extensive ESI-MS studies on solutions and solids of the reaction led to the proposal consisting of an initial stepwise assembly of Mn4 L4 from the reactants via [MnL] and [Mn2 L2 ] below 80 °C, and then disassembly to [MnL] and [MnL2 ] followed by ligand modification before reassembly to Mn4 L'6 via [MnL'], [MnL'2 ], and [Mn2 L'3 ] with increasing solvothermal temperature up to 140 °C. Identification of intermediates [Mn4 Lx L'6-x ] (x=5, 4, 3, 2, 1) in the process further suggested an assembly/disassembly/in situ reaction/reassembly transformation mechanism. These results not only reveal that multiple phase transformations are possible even though they were not realized in the crystalline state, but also help to better understand the complex transformation process between coordination clusters during "black-box" reactions.

Tris(ß-ketoiminato)ruthenium(III) - Structural and electronic data of the neutral, oxidized and reduced forms.

In this data article, density functional theory (DFT) calculated data for the optimized geometries and electronic structure data of the neutral, oxidized and reduced forms of the fac and mer isomers of tris(amino-pent-3-en-2-onato-N,O)ruthenium(III) as representative example of tris(ß-ketoiminato)ruthenium(III) complexes is provided. Energy-level diagrams of the neutral, oxidized and reduced molecules, show the effect on the molecular energy levels and the electron occupation of the frontier orbitals, when the neutral complex is oxidized or reduced. The DFT calculated data also confirms the spin state of the molecules and show that the fac and mer isomers of tris(amino-pent-3-en-2-onato-N,O)ruthenium(III) are equi-energetic.

Synthesis, Structural Characterization and Antimicrobial Evaluation of Ruthenium Complexes with Heteroaromatic Carboxylic Acids.

The antibacterial and antibiofilm activities of two new ruthenium complexes against E. coli, S. aureus, P. aeruginosa PAO1 (laboratory strain) and P. aeruginosa LES B58 (clinical strain) were evaluated. Complexes, mer-[RuIII (2-bimc)3 ] ⋅ H2 O (1) and cis-[RuIV Cl2 (2,3-pydcH)2 ] ⋅ 4H2 O (2), were obtained using aromatic carboxylic acid ligands, namely, 1H-benzimidazole-2-carboxylic acid (2-bimcH) and pyridine-2,3-dicarboxylic acid (2,3-pydcH2 ). Compounds were physicochemically characterized using X-ray diffraction, Hirshfeld surface analysis, IR and UV/VIS spectroscopies, as well as magnetic and electrochemical measurements. Structural characterization revealed that Ru(III) and Ru(IV) ions in the complexes adopt a distorted octahedral geometry. The intermolecular classical and weak hydrogen bonds, and π⋅⋅⋅π contacts significantly contribute to structure stabilization, leading to the formation of a supramolecular assembly. Biological studies have shown that the Ru complexes inhibit the growth of bacteria and biofilm formation by the tested strains and the complexes seem to be a potential as antimicrobial agents.

A Hybrid Anion for Ionic Liquid and Battery Electrolyte Applications: Half Triflamide, Half Carbonate.

The synthesis of a new imide type anion, methylcarbonate(trifluoromethylsulfonyl)imide (MCTFSI) is described and the physicochemical properties of its sodium and N-butyl-N-methyl pyrrolidinium salts as well as structural information obtained by X-ray diffraction studies of the sodium salt are discussed in terms of charge delocalisation, coordination chemistry and electrochemical behaviour with respect to the analogous imdides bis(trifluoromethanesulfonyl)imide (TFSI) and bis(fluorosulfonyl)imide (FSI). The insight obtained from studying the new anion informs and reemphasizes the concept of weakly coordinating anions and coordination chemistry in designing electrolyte salts.

Synthesis and Characterization of Oxazaborinin Phosphonate for Blue OLED Emitter Applications.

A blue-light emitting material based on a boron complex containing heteroaromatic phosphonate ligand is synthesized and characterized. The Phospho-Fries rearrangement is used in the synthesis route of the ligand as a convenient method of introducing phosphonate groups into phenols. Structural, thermal and photophysical properties of the resulting oxazaborinin phosphonate compound have been characterized. DFT geometry optimizations were studied as well as the spatial position and symmetry of the HOMO and LUMO. Good thermal stability up to 250 °C enables vacuum deposition methods next to solution processing. Combining the work function with the optical band gap from UV-Vis measurements shows that band alignment is possible with standard contact materials. Photoluminescence reveals an emission peak at 428 nm, which is suitable for a blue light-emitter.

High-Spin Mononuclear Iron(III) Complexes with Pentadentate Schiff Base Ligands: Structural Analysis and Magnetic Properties.

Various substituted 2-hydroxybenzophenones were combined with aliphatic linear triamines to form pentadentate Schiff base ligands. Twelve new iron(III) complexes with the general formula [Fe(Ln )X].mCH3 CN (n=1-10; X=N3- , NCS- or NCSe- ; m=0-2) have been synthesized, and spectrally as well as structurally characterized. The structural analysis revealed a notable dependence of coordination polyhedra deformation as well as the spatial configuration of donor atoms on the length and symmetry of the Schiff base ligands. The magnetic properties of the compounds were investigated and the permanent high-spin state (S=5/2) for all reported compounds was established, and allowed calculation of zero-field-splitting parameters as well as coupling constants, which were further confirmed with DFT calculations. The solid-state EPR spectra were recorded at 293 K and 98 K, and in accordance with the magnetic measurements, showed a high-spin state in the measured temperature range.

Cis versus Trans: The Coordination Environment about the Tin(IV) Atom in Spirocyclic Amino Alcohol Derivatives.

The syntheses of amino alcohols MeN(CH2 CH2 CMe2 OH)2 (1), MeN(CMe2 CH2 OH)(CH2 CMe2 OH) (2), MeN(CH2 CH2 CH2 OH)(CH2 CMe2 OH) (3), MeN(CH2 CH2 CMe2 OH)(CH2 CMe2 OH) (4), MeN(CH2 CH2 CMe2 OH)(CH2 CH2 OH) (5), and MeN(CH2 CH2 OH) (CH2 CH2 CH2 OH) (6) as well as spirocyclic tin(IV) alkoxides spiro-[nBuN(CH2 CMe2 O)2 ]2 Sn (7), spiro-[MeN(CH2 CH2 CMe2 O)2 ]2 Sn (8), spiro-[para-FC6 H4 N (CH2 CMe2 O)2 ]2 Sn (9), spiro-[MeN(CMe2 CH2 O)(CH2 CMe2 O)]2 Sn (10), spiro-[MeN(CH2 CH2 CH2 O)(CH2 CMe2 O)]2 Sn (11), spiro-[MeN(CH2 CH2 CMe2 O)(CH2 CMe2 O)]2 Sn (12), spiro-[MeN(CH2 CH2 CMe2 O)(CH2 CH2 O)]2 Sn (13) and spiro-[MeN(CH2 CH2 O)(CH2 CH2 CH2 O)]2 Sn (14) are reported. The compounds were characterized by 1 H, 13 C (1-14) and 119 Sn (7-14) NMR and IR spectroscopy, EIMS and single-crystal XRD (2, 7-10 and 13, 14). Graph-set analyses were performed for compounds [(MeNH(CMe2 CH2 OH)(CH2 CMe2 OH)][HC(O)O] (2 a) and 2. The coordination environment about the tin(IV) centre of the spirocyclic compounds and their possible stereoisomers were analysed by DFT calculations (spiro-[MeN(CH2 CMe2 O)2 ]2 Sn, 8-10 and 13).