NHC-Stabilized 1,2-Dihalodiborenes: Synthesis, Characterization, and Reactivity Toward Elemental Chalcogens.

The 2-fold reduction of B2X4(NHC)2 (X = Cl, Br, I; NHC = (un)saturated N-heterocyclic carbene) yields the corresponding green-colored 1,2-dihalodiborenes B2X2(NHC)2, the 11B NMR resonances of which are strongly upfield-shifted upon descending the halide group. The diborenes crystallize as the trans isomers, with relatively short B═B double bonds (1.513(9) to 1.568(4) Å). Cyclic voltammetric experiments with these diborenes reveal reversible one-electron oxidation processes to the corresponding diboron radical cation (E1/2 = -1.16 to -1.50 V); the reducing power of B2X2(NHC)2 increasing with the electronegativity of the halide and for the less π-accepting unsaturated NHCs. The main UV-vis absorption (393-463 nm), which corresponds mainly to a highest occupied molecular orbital (HOMO) → lowest unoccupied molecular orbital (LUMO) transition, undergoes a blueshift upon descending the halide group and shows some dependence on the stereoelectronics of the NHC ligands. Computational analyses show that the HOMO of B2X2(NHC)2 is mostly localized on the B═B π bond, with the contribution from halide p orbitals decreasing down the group, and the saturated NHCs affording some π-bonding delocalization over the B-CNHC bonds. The calculated HOMO and LUMO energies decrease upon descending the halide group, while the HOMO-LUMO gap also decreases, correlating well with the cyclovoltammetry and UV-vis data. The reactions of B2Br2(NHC)2 with elemental sulfur and red selenium lead to the formation of the corresponding diborathiiranes and seleniranes, respectively, which were characterized by NMR and UV-vis spectroscopy, cyclic voltammetry, and X-ray diffraction analyses. In one case, an additional one-electron oxidation yields a unique cyclic B2Se radical cation. Computational analyses show that the localization of the HOMO and HOMO - 1 of the diboraseleniranes is inverted compared to the diborathiiranes.

Stable Lewis Base Adducts of Tetrahalodiboranes: Synthetic Methods and Structural Diversity.

A series of 22 new bis(phosphine), bis(carbene), and bis(isonitrile) tetrahalodiborane adducts has been synthesized, either by direct adduct formation with highly sensitive B2 X4 precursors (X=Cl, Br, I) or by ligand exchange at stable B2 X4 (SMe2 )2 precursors (X=Cl, Br) with labile dimethylsulfide ligands. The isolated compounds have been fully characterized using NMR spectroscopy, elemental analysis, and, for 20 of these compounds, single-crystal X-ray diffraction, revealing an unexpected variation in the bonding motifs. In addition to the classical B2 X4 L2 diborane(4) bis-adducts, certain more sterically demanding carbene ligands induce a halide displacement which led to the first halide-bridged monocationic diboron species, [B2 X3 L2 ]A (A=BCl4 , Br, I). Furthermore, low-temperature 1:1 reactions of B2 Cl4 with sterically demanding N-heterocyclic carbenes led to the formation of kinetically unstable mono-adducts, one of which was structurally characterized. A comparison of the NMR spectra and structural data of new and literature-known bis-adducts shows several trends pertaining to the nature of the halides and the stereoelectronic properties of the Lewis bases employed.

New Outcomes of Beryllium Chemistry: Lewis Base Adducts for Salt Elimination Reactions.

A range of mono- and bis-adducts of beryllium dichloride with cyclic (alkyl)(amino)carbenes (CAAC), cyclic diamidocarbene (DAC), and carbodiphosphorane (CDP) are prepared, and their reactions with nucleophiles are studied. Salt elimination with Yamashita and Nozaki's lithium diazaborolide reagent led to the isolation of an unsymmetrical beryllium diazaborolyl complex and a base-stabilized diazaborolyl beryllium chloride. From structural and spectroscopic analyses, the Be-B bonding in these compounds was determined to be polar covalent in character. In addition, the nucleophilic addition of magnesium anthracenediyl to one of the adducts resulted in the isolation of an interesting tetracyclic beryllium-bridged molecule.

Simple solution-phase syntheses of tetrahalodiboranes(4) and their labile dimethylsulfide adducts.

Convenient solution-phase syntheses of tetrahalodiboranes(4) B2F4, B2Cl4 and B2I4 are presented herein from common precursor B2Br4. In addition, the dimethylsulfide adducts B2Cl4(SMe2)2 and B2Br4(SMe2)2 are conveniently prepared in one-step gram and multigram scale syntheses from the commercially-available starting material B2(NMe2)4. The results provide simple access to the full range of tetrahalodiboranes(4) for the exploration of their untapped synthetic potential.

Strongly Phosphorescent Transition Metal π-Complexes of Boron-Boron Triple Bonds.

Herein are reported the first π-complexes of compounds with boron-boron triple bonds with transition metals, in this case CuI. Three different compounds were isolated that differ in the number of copper atoms bound to the BB unit. Metalation of the B-B triple bonds causes lengthening of the B-B and B-CNHC bonds, as well as large upfield shifts of the 11B NMR signals, suggesting greater orbital interactions between the boron and transition metal atoms than those observed with recently published diboryne/alkali metal cation complexes. In contrast to previously reported fluorescent copper(I) π-complexes of boron-boron double bonds, the Cun-π-diboryne compounds (n = 2, 3) show intense phosphorescence in the red to near-IR region from their triplet excited states, according to their microsecond lifetimes, with quantum yields of up to 58%. While the Cu diborene bond is dominated by electrostatic interactions, giving rise to S1 and T1 states of pure IL(π-π*) nature, DFT studies show that the CuI π-complexes of diborynes reported herein exhibit enhanced metal d orbital contributions to HOMO and HOMO-1, which results in S1 and T1 having significant MLCT character, enabling strong spin-orbit coupling for highly efficient intersystem-crossing S1 → Tn and phosphorescence T1 → S0.

Neutral zero-valent s-block complexes with strong multiple bonding.

The metals of the s block of the periodic table are well known to be exceptional electron donors, and the vast majority of their molecular complexes therefore contain these metals in their fully oxidized form. Low-valent main-group compounds have recently become desirable synthetic targets owing to their interesting reactivities, sometimes on a par with those of transition-metal complexes. In this work, we used stabilizing cyclic (alkyl)(amino)carbene ligands to isolate and characterize the first neutral compounds that contain a zero-valent s-block metal, beryllium. These brightly coloured complexes display very short beryllium-carbon bond lengths and linear beryllium coordination geometries, indicative of strong multiple Be-C bonding. Structural, spectroscopic and theoretical results show that the complexes adopt a closed-shell singlet configuration with a Be(0) metal centre. The surprising stability of the molecule can be ascribed to an unusually strong three-centre two-electron π bond across the C-Be-C unit.

A Binuclear 1,1'-Bis(boratabenzene) Complex: Unprecedented Intramolecular Metal-Metal Communication through a B-B Bond.

We report the synthesis of the first 1,1'-bis(boratabenzene) species by tetrabromodiborane(4)-induced ring-expansion reactions of cobaltocene. Six equivalents of cobaltocene are required as the species plays the dual role of reagent and reductant to yield [{(η(5) -C5 H5 )Co}2 {µ:η(6) ,η(6) -(BC5 H5 )2 }]. The formally dianionic bis(boratabenzene) moiety with a boron-boron single bond can be viewed as a symmetric dimer of the parent boratabenzene anion as well as the first example of a diboron analogue of biphenyl. The solution electrochemistry of the bimetallic complex shows four stepwise redox events, indicating significant intramolecular interaction between the cobalt ions across the 1,1'-bis(boratabenzene) unit. The magnetic properties, as investigated by variable-temperature SQUID magnetometry, reveal weak intramolecular antiferromagnetic interactions. Density functional theory calculations support the experimental results and add insight into the various electronic states of the complex.

The Synthesis of B2(SIDip)2 and its Reactivity Between the Diboracumulenic and Diborynic Extremes.

A new compound with the formula L-B2-L wherein the stabilizing ligand (L) is 1,3-bis[diisopropylphenyl]-4,5-dihydroimidazol-2-ylidene (SIDip) has been synthesized, isolated, and characterized. The π-acidity of the SIDip ligand, intermediate between the relatively non-acidic IDip (1,3-bis[diisopropylphenyl]imidazol-2-ylidene) ligand and the much more highly acidic CAAC (1-[2,6-diisopropylphenyl]-3,3,5,5-tetramethylpyrrolidin-2-ylidene) ligand, gives rise to a compound with spectroscopic, electrochemical, and structural properties between those of L-B2-L compounds stabilized by CAAC and IDip. Reactions of all three L-B2-L compounds with CO demonstrate the differences caused by their respective ligands, as the π-acidities of the CAAC and SIDip carbenes enabled the isolation of bis(boraketene) compounds (L(OC)B-B(CO)L), which could not be isolated from reactions with B2(IDip)2. However, only B2(IDip)2 and B2(SIDip)2 could be converted into bicyclic bis(boralactone) compounds.

Exclusive π Encapsulation of Light Alkali Metal Cations by a Neutral Molecule.

Cation-π interactions are one of the most important classes of noncovalent bonding, and are seen throughout biology, chemistry, and materials science. However, in almost every documented case, these interactions play only a supporting role to much stronger covalent or dative bonds, thus making examples of exclusive cation-π bonding exceedingly rare. In this study, a neutral diboryne molecule is found to encapsulate the light alkali metal cations Li(+) and Na(+) in the absence of a net charge, covalent bonds, or lone-pair donor groups. The resulting encapsulation complexes are, to our knowledge, the first structurally authenticated species in which a neutral molecule binds the light alkali metals exclusively through cation-π interactions.

Experimental assessment of the strengths of B-B triple bonds.

Diborynes, molecules containing homoatomic boron-boron triple bonds, have been investigated by Raman spectroscopy in order to determine the stretching frequencies of their central B≡B units as an experimental measure of homoatomic bond strengths. The observed frequencies between 1600 and 1750 cm(-1) were assigned on the basis of DFT modeling and the characteristic pattern produced by the isotopic distribution of boron. This frequency completes the series of known stretches of homoatomic triple bonds, fitting into the trend established by the long-known stretching frequencies of C≡C and N≡N triple bonds in alkynes and dinitrogen, respectively. A quantitative analysis was carried out using the concept of relaxed force constants. The results support the classification of the diboryne as a true triple bond and speak to the similarities of molecules constructed from first-row elements of the p block. Also reported are the relaxed force constants of a recently reported diborabutatriene, which again fit into the trend established by the vibrational spectroscopy of organic cumulenes. As part of these studies, a new diboryne with decreased steric bulk was synthesized, and a computational study of the rotation of the stabilizing ligands indicated alkyne-like electronic isolation of the central B2 unit.

Diborabutatriene: an electron-deficient cumulene.

The complexation of two equivalents of a cyclic (alkyl)(amino)carbene (CAAC) to tetrabromodiborane, followed by reduction with four equivalents of sodium naphthalide, led to the formation of the CAAC-stabilized linear diboracumulene (CAAC)2B2. The capacity of the CAAC ligand to facilitate B2 →CAAC donation of π-electron density resulted in important differences between this species and a previously reported complex featuring a B≡B triple bond stabilized by cyclic di(amino)carbenes, including a longer B-B bond and shorter B-C bonds. Frontier orbital analysis indicated sharing of valence electrons across the entire linear C-B-B-C unit in (CAAC)2B2, which is supported by natural population analysis and cyclic voltammetry.

Metal-free binding and coupling of carbon monoxide at a boron-boron triple bond.

Many metal-containing compounds, and some metal-free compounds, will bind carbon monoxide. However, only a handful of metal-containing compounds have been shown to induce the coupling of two or more CO molecules, potentially a method for the use of CO as a one-carbon-atom building block for the synthesis of organic molecules. In this work, CO was added to a boron-boron triple bond at room temperature and atmospheric pressure, resulting in a compound into which four equivalents of CO are incorporated: a flat, bicyclic, bis(boralactone). By the controlled addition of one CO to the diboryne compound, an intermediate in the CO coupling reaction was isolated and structurally characterized. Electrochemical measurements confirm the strongly reducing nature of the diboryne compound.

Ambient-temperature isolation of a compound with a boron-boron triple bond.

Homoatomic triple bonds between main-group elements have been restricted to alkynes, dinitrogen, and a handful of reactive compounds featuring trans-bent heavier elements of groups 13 and 14. Previous attempts to prepare a compound with a boron-boron triple bond that is stable at ambient temperature have been unsuccessful, despite numerous computational studies predicting their viability. We found that reduction of a bis(N-heterocyclic carbene)-stabilized tetrabromodiborane with either two or four equivalents of sodium naphthalenide, a one-electron reducing agent, yields isolable diborene and diboryne compounds. Crystallographic and spectroscopic characterization confirm that the latter is a halide-free linear system containing a boron-boron triple bond.

Synthesis and structure of distanna and tristanna ansa half-sandwich complexes of ruthenium and nickel.

The synthesis and structural characterization of the first tin-bridged ansa half-sandwich complexes via a two-step protocol from Na[η(5)-C(5)H(5)Ru(CO)(2)] and in situ generated Na[η(5)-C(5)H(5)Ni(CO)] are presented. Both compounds are characterized by multinuclear NMR spectroscopy and single-crystal diffraction.

Sterically demanding hetero-substituted [2]borametallocenophanes of group IV metals: synthesis, structure and reactivity.

We report the synthesis and characterisation of unprecedented unstrained [2]diborametallocenophanes of zirconium and hafnium that bear the bulky octamethylfluorenyl (η(5)-C(29)H(36)) system, the proligands of which were pre-constructed by a two-step synthesis. The compounds were fully characterised by NMR spectroscopy, MALDI-TOF mass spectrometry and X-ray diffraction analysis. Typical reactivities relevant to olefin polymerisation such as methylation and chloride abstraction were also investigated. Finally, a sterically demanding bis(octamethylfluorenyl) metallocene was prepared.

A novel class of potent NF-kappaB signaling inhibitors.

A novel class of NF-kappaB pathway signaling inhibitors was discovered by virtual screening, medicinal chemistry, and QSAR analysis. An initial set of compounds inhibited NF-kappaB signaling in a whole cell reporter gene assay in the micro-molar range. Activity was improved step by step by medicinal chemistry to yield nano-molar signaling inhibitors.

Dual binding mode of a novel series of DHODH inhibitors.

Human dihydroorotate dehydrogenase (DHODH) represents an important target for the treatment of hyperproliferative and inflammatory diseases. In the cell DHODH catalyzes the rate-limiting step of the de novo pyrimidine biosynthesis. DHODH inhibition results in beneficial immunosuppressant and antiproliferative effects in diseases such as rheumatoid arthritis. Here, we present high-resolution X-ray structures of human DHODH in complex with a novel class of low molecular weight compounds that inhibit the enzyme in the nanomolar range. Some compounds showed an interesting dual binding mode within the same cocrystal strongly depending on the nature of chemical substitution. Measured in vitro activity data correlated with the prevailing mode of binding and explained the observed structure-activity relationship. Additionally, the X-ray data confirmed the competitive nature of the inhibitors toward the putative ubiquinone binding site and will guide structure-based design and synthesis of molecules with higher activity.

Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH inhibitors.

A previously discovered DHODH inhibitor series was further improved by replacing the cyclopentene ring by aromatic heterocycles. Different isomers of these compounds were prepared by the directed ortho-metallation procedure. The compounds are more active than the corresponding cyclopentene analogs and show potent effects on PBMC's proliferation.

SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors.

Novel DHODH inhibitors were developed based on a previously described series by introduction of heteroatoms into the cyclopentene ring and hydroxyl groups attached to it. Also, the hydrophobic biphenyl side chain was replaced with benzyloxy phenyl groups. Activities on human, rat, and mouse enzymes indicate a species specificity of these inhibitors.

Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis.

In an approach to discover new inhibitors of trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas' disease, a virtual high-throughput screening was performed. Two structurally new types of inhibitors emerged, the antimicrobial chlorhexidine {1,1'-hexamethylenebis[5-(4-chlorophenyl)biguanide]}, a linear competitive inhibitor (K(i) = 2 +/- 1 microM), and a piperidine derivative acting as mixed inhibitor (K(i) = 6.2 +/- 2 microM and K(i)' = 8.5 +/- 2 microM). Neither compound interferes with human glutathione reductase. Based on chlorhexidine, different series of compounds were synthesized and studied as inhibitors of T. cruzi trypanothione reductase. Most efficient derivatives were three bis(amidines) showing mixed type inhibition with K(i,slope) and K(i,int) values of 2-5 microM and 16-47 microM, respectively. Although these compounds did not exert an improved inhibitory potency compared to chlorhexidine, the change from competitive to mixed-type inhibition is advantageous, since substrate accumulation does not overcome inhibition. Remarkably, all three derivatives carried two copies of an identical 2-methoxy-4-methyl-1-(phenylmethoxy)benzene substituent.