A New Class of Remote N‐Heterocyclic Carbenes with Exceptionally Strong σ‐Donor Properties: Introducing Benzo[c]quinolin‐6‐ylidene

We make the case for benzo[c]quinolin‐6‐ylidene ( 1 ) as a strongly electron‐donating carbene ligand. The facile synthesis of 6‐trifluoromethanesulfonylbenzo[c]quinolizinium trifluoromethanesulfonate ( 2 ) gives straightforward access to a useful precursor for oxidative addition to low‐valent metals, to yield the desired carbene complexes. This concept has been achieved in the case of [Mn(benzo[c]quinolin‐6‐ylidene)(CO)₅]⁺ ( 15 ) and [Pd(benzo[c]quinolin‐6‐ylidene)(PPh₃)₂(L)]²⁺ L=THF ( 21 ), OTf ( 22 ) or pyridine ( 23 ). Attempts to coordinate to nickel result in coupling products from two carbene precursor fragments. The CO IR‐stretching‐frequency data for the manganese compound suggests benzo[c]quinolin‐6‐ylidene is at least as strong a donor as any heteroatom‐stabilised carbene ligand reported.     

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results

PURPOSE: The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K(trans) (volume transfer constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes post-treatment. RESULTS: Significant (P < .05) changes or trends towards significance (P < .10) were seen in all parameters except tau(i), although there was qualitative reduction in tau(i) values post-treatment. In particular, there was reduction (P < .035) in voxels with K(trans) values in the range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively correlated (r = -.60, P < .02). Parameters sensitive to water distribution and geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear regression model. CONCLUSION: The analysis presented here is sensitive to longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.     

Cycloadditions of 1H-1,3-Benzazaphospholes with o-Chloranil

NH-Functional 1H-1,3-benzazaphospholes 1a–1c and o-chloranil (tetrachloro-o-benzoquinone - TCBQ) undergo rapid [1+4]-cycloaddition in a 1:2 molar ratio to give 2a – 2c as high-melting zwitterionic σ⁶λ⁵-phosphorus compounds. In the case of 2a the yield is high (rel. to TCBQ) even if the reactants were used in a 1:0.5 molar ratio. For the 2-tert-butyl-substituted compounds 2b and 2c the yields were significantly lower, in part by unidentified byproducts. Addition of excess TCBQ to crude 2c containing unconverted 1c did not increase but strongly decrease the amount of 2c . Crystallization and XRD analysis led to detection of a minor side or consecutive product 3c , formally corresponding to P=C bond cleavage and [1+4] cycloaddition of three equivalents TCBQ, two at the phosphinidene and one at the carbene end. NMR spectroscopic data of 2a – 2c including conclusive ¹³C data for 2a give evidence of the structures of the new compounds.     

Enantioselective Synthesis of a Tricyclic,sp3-Rich Diazatetradecanedione: an Amino Acid-Based Natural Product-Like Scaffold

6-, 7-, and 8-membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.0^{4, 9}]-tetradecanedione scaffold. Advanced building blocks based on d -aspartic acid and l -pyroglutamic acid were combined by a sp³−sp² Negishi coupling. A carbamate-guided syn-diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one-pot hydroxyl-group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp³-rich tricycle. The final compound is a substrate mimic of peptidyl-prolyl cis-trans isomerases featuring a locked trans-amide bond. Cheminformatic analysis of 179 virtual derivatives indicates favourable physicochemical properties and drug-like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506-binding protein 12.     

The Diversity of a Polyclonal FluCell-SELEX Library Outperforms Individual Aptamers as Emerging Diagnostic Tools for the Identification of Carbapenem Resistant Pseudomonas aeruginosa

Textbook procedures require the use of individual aptamers enriched in SELEX libraries which are subsequently chemically synthesized after their biochemical characterization. Here we show that this reduction of the available sequence space of large libraries and thus the diversity of binding molecules reduces the labelling efficiency and fidelity of selected single aptamers towards different strains of the human pathogen Pseudomonas aeruginosa compared to a polyclonal aptamer library enriched by a whole-cell-SELEX involving fluorescent aptamers. The library outperformed single aptamers in reliable and specific targeting of different clinically relevant strains, allowed to inhibit virulence associated cellular functions and identification of bound cell surface targets by aptamer based affinity purification and mass spectrometry. The stunning ease of this FluCell-SELEX and the convincing performance of the P. aeruginosa specific library may pave the way towards generally new and efficient diagnostic techniques based on polyclonal aptamer libraries not only in clinical microbiology.     

Oxidized Hemithioindigo Photoswitches—Influence of Oxidation State on (Photo)physical and Photochemical Properties

The photophysical and photochemical properties of sulfoxide and sulfone derivatives of hemithioindigo photoswitches are scrutinized and compared to the unoxidized parent chromophores. Oxidation results in significantly blue-shifted absorptions and mostly reduction of photochromism while thermal stabilities of individual isomers remain largely unaltered. Effective photoswitching takes place at shorter wavelengths compared to parent hemithioindigos and high isomeric yields can be obtained reversibly in the respective photostationary states. Reversible solid-state photoswitching is observed for a twisted sulfone derivative accompanied by visible color changes. These results establish oxidized hemithioindigo photoswitches as promising and versatile tools for robust light-control of molecular behavior for a wide range of applications.     

Active and Unidirectional Acceleration of Biaryl Rotation by a Molecular Motor

Light‐driven molecular motors possess immense potential as central driving units for future nanotechnology. Integration into larger molecular setups and transduction of their mechanical motions represents the current frontier of research. Herein we report on an integrated molecular machine setup allowing the transmission of potential energy from a motor unit onto a remote receiving entity. The setup consists of a motor unit connected covalently to a distant and sterically encumbered biaryl receiver. By action of the motor unit, single‐bond rotation of the receiver is strongly accelerated and forced to proceed unidirectionally. The transmitted potential energy is directly measured as the extent to which energy degeneration is lifted in the thermal atropisomerization of this biaryl. Energy degeneracy is reduced by more than 1.5 kcal mol^?1, and rate accelerations of several orders of magnitude in terms of the rate constants are achieved.     

A Flexible Photoactive Titanium Metal–Organic Framework Based on a [TiIV3(μ3‐O)(O)2(COO)6] Cluster

The synthesis of titanium–carboxylate metal–organic frameworks (MOFs) is hampered by the high reactivity of the commonly employed alkoxide precursors. Herein, we present an innovative approach to titanium‐based MOFs by the use of titanocene dichloride to synthesize COK‐69, the first breathing Ti MOF, which is built up from trans‐1,4‐cyclohexanedicarboxylate linkers and an unprecedented [Ti^IV₃(μ₃‐O)(O)₂(COO)₆] cluster. The photoactive properties of COK‐69 were investigated in depth by proton‐coupled electron‐transfer experiments, which revealed that up to one Ti^IV center per cluster can be photoreduced to Ti^III while preserving the structural integrity of the framework. The electronic structure of COK‐69 was determined by molecular modeling, and a band gap of 3.77 eV was found.     

Coinage Metal Complexes of Bis(quinoline-2-ylmethyl)phenylphosphine-Simple Reactions Can Lead to Unprecedented Results

The different coordination behavior of the flexible yet sterically demanding, hemilabile P,N ligand bis(quinoline-2-ylmethyl)phenylphosphine ( bqmpp ) towards selected Cu^I, Ag^I and Au^I species is described. The resulting X-ray crystal structures reveal interesting coordination geometries. With [Cu(MeCN)₄]BF₄, compound 1 [Cu₂(bqmpp)₂](BF₄)₂ is obtained, wherein the copper(I) atoms display a distorted square planar and square pyramidal geometry. The steric demand and π-stacking of the ligand allow for a short Cu⋅⋅⋅Cu distance (2.588(9) Å). Cu^I complex 2 [Cu₄Cl₃(bqmpp)₂]BF₄ contains a rarely observed Cu₄Cl₃ cluster, probably enabled by dichloromethane as the chloride source. In the cluster, even shorter Cu⋅⋅⋅Cu distances (2.447(1) Å) are present. The reaction of Ag[SbF₆] with the ligand leads to a dinuclear compound ( 3 ) in solution as confirmed by ³¹P{¹H} NMR spectroscopy. During crystallization, instead of the expected phosphine complex 3 , a tris(quinoline-2-ylmethyl)bisphenyl-phosphine ( tqmbp ) compound [Ag₂(tqmbp)₂](SbF₆)₂ 4 is formed by elimination of quinaldine. The Au(I) compound [Au₂(bqmpp)₂]PF₆ ( 5 ) is prepared as expected and shows a linear arrangement of two phosphine ligands around Au^I.