@unpublished{YinWernerHiguchietal.2018, author = {Yin, Yafu and Werner, Rudolf A. and Higuchi, Takahiro and Lapa, Constantin and Pienta, Kenneth J. and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P.}, title = {Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.118.217653}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167594}, year = {2018}, abstract = {Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa. Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9\%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3\%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy. Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7\%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0\%) PSMA-RADS-3A lesions and 3/14 (21.4\%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @unpublished{WernerIlhanLehneretal.2018, author = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.}, title = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy}, series = {Molecular Imaging and Biology}, journal = {Molecular Imaging and Biology}, issn = {1536-1632}, doi = {https://doi.org/10.1007/s11307-018-1252-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164624}, year = {2018}, abstract = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @unpublished{WernerBundschuhBundschuhetal.2018, author = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Leal, Jeffrey P. and Higuchi, Takahiro and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.}, title = {Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.118.217588}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167788}, year = {2018}, abstract = {Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4\%) instances, three readers in 40/125 (32\%) and two observers in 27/125 (21.6\%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005). Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @unpublished{WernerAndreeJavadietal.2018, author = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.}, title = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging}, series = {Urology - The Gold Journal}, journal = {Urology - The Gold Journal}, issn = {0090-4295}, doi = {10.1016/j.urology.2018.03.030}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161103}, year = {2018}, abstract = {No abstract available.}, subject = {Virchow Node}, language = {en} } @unpublished{TitovHumeniukMitric2018, author = {Titov, Evgenii and Humeniuk, Alexander and Mitric, Roland}, title = {Exciton localization in excited-state dynamics of a tetracene trimer: A surface hopping LC-TDDFTB study}, series = {Physical Chemistry Chemical Physics}, journal = {Physical Chemistry Chemical Physics}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198680}, year = {2018}, abstract = {Excitons in the molecular aggregates of chromophores are key participants in important processes such as photosynthesis or the functioning of organic photovoltaic devices. Therefore, the exploration of exciton dynamics is crucial. Here we report on exciton localization during excited-state dynamics of the recently synthesized tetracene trimer [Liu et al., Org. Lett., 2017, 19, 580]. We employ the surface hopping approach to nonadiabatic molecular dynamics in conjunction with the long-range corrected time-dependent density functional tight binding (LC-TDDFTB) method [Humeniuk and Mitrić, Comput. Phys. Commun., 2017, 221, 174]. Utilizing a set of descriptors based on the transition density matrix, we perform comprehensive analysis of exciton dynamics. The obtained results reveal an ultrafast exciton localization to a single tetracene unit of the trimer during excited-state dynamics, along with exciton transfer between units.}, language = {en} } @unpublished{StoyBoehnkeJiménezHallaetal.2018, author = {Stoy, Andreas and B{\"o}hnke, Julian and Jiménez-Halla, J. Oscar C. and Dewhurst, Rian D. and Thiess, Torsten and Braunschweig, Holger}, title = {CO\(_2\) Binding and Splitting by Boron-Boron Multiple Bonds}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201802117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164265}, year = {2018}, abstract = {CO\(_2\) is found to undergo room-temperature, ambient- pressure reactions with two species containing boron-boron multiple bonds, leading to incorporation of either one or two CO\(_2\) molecules. In one case, a thermally-unstable intermediate was structurally characterized, indicating the operation of an initial 2+2 cycloaddition mechanism in the reaction.}, language = {en} } @unpublished{StennettMattockVollertetal.2018, author = {Stennett, Tom and Mattock, James and Vollert, Ivonne and Vargas, Alfredo and Braunschweig, Holger}, title = {Unsymmetrical, Cyclic Diborenes and Thermal Rearrangement to a Borylborylene}, series = {Angewandte Chemie, International Edition}, volume = {57}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201800671}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-160258}, pages = {4098-4102}, year = {2018}, abstract = {Cyclic diboranes(4) based on a chelating monoanionic, benzylphosphine linker were prepared by boron-silicon exchange between arylsilanes and B\(_2\)Br\(_4\). Coordination of Lewis bases to the remaining sp\(^2\) boron atom yielded unsymmetrical sp\(^3\)-sp\(^3\) diboranes, which were reduced with KC\(_8\) to their corresponding trans-diborenes. These compounds were studied by a combination of spectroscopic methods, X-ray diffraction and DFT calculations. PMe\(_3\)-stabilized diborene 6 was found to undergo thermal rearrangement to gem- diborene 8. DFT calculations on 8 reveal a polar boron-boron bond, and indicate that the compound is best described as a borylborylene.}, language = {en} } @unpublished{StennettMattockPentecostetal.2018, author = {Stennett, Tom and Mattock, James and Pentecost, Leanne and Vargas, Alfredo and Braunschweig, Holger}, title = {Chelated Diborenes and their Inverse-Electron-Demand Diels- Alder Reactions with Dienes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201809217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178268}, year = {2018}, abstract = {A doubly base-stabilized diborane based on a benzylphosphine linker was prepared by a salt elimination reaction between 2-LiC\(_6\)H\(_4\)CH\(_2\)PCy\(_2\).Et\(_2\)O and B\(_2\)Br\(_4\). This compound was reduced with KC8 to its corresponding diborene, with the benzylphosphine forming a five-membered chelate. The diborene reacts with butadiene, 2-trimethylsiloxy-1,3-butadiene and isoprene to form 4,5-diboracyclohexenes, which interconvert between their 1,1- (geminal) and 1,2- (vicinal) chelated isomers. The 1,1-chelated diborene undergoes a halide-catalysed isomerisation into its thermodynamically favoured 1,2-isomer, which undergoes Diels-Alder reactions more slowly than the kinetic product.}, language = {en} } @unpublished{StennettBertermannBraunschweig2018, author = {Stennett, Tom and Bertermann, R{\"u}diger and Braunschweig, Holger}, title = {Construction of Linear and Branched Tetraboranes via 1,1- and 1,2-Diboration of Diborenes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201809976}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178276}, year = {2018}, abstract = {Sterically unencumbered diborenes based on a benzylphosphine chelate undergo diboration reactions with bis(catecholato)diboron in the absence of a catalyst to yield tetraboranes. The symmetrical diborenes studied undergo 1,2- diborations, whereas an unsymmetrical derivative was found to yield a triborylborane-phosphine adduct as the result of a formal 1,1-diboration. A related borylborylene compound also underwent a 1,2-diboration to produce a borylene-borane adduct.}, language = {en} } @unpublished{SednevMykhailiukChoudhuryetal.2018, author = {Sednev, Maksim V. and Mykhailiuk, Volodymyr and Choudhury, Priyanka and Halang, Julia and Sloan, Katherine E. and Bohnsack, Markus T. and H{\"o}bartner, Claudia}, title = {N\(^6\)-methyladenosine-sensitive RNA-cleaving deoxyribozymes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {https://doi.org/10.1002/anie.201808745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171753}, year = {2018}, abstract = {Deoxyribozymes are synthetic enzymes made of DNA that can catalyze the cleavage or formation of phosphodiester bonds and are useful tools for RNA biochemistry. Here we report new RNA-cleaving deoxyribozymes to interrogate the methylation status of target RNAs, thereby providing an alternative method for the biochemical validation of RNA methylation sites containing N\(^6\)-methyladenosine, which is the most wide-spread and extensively investigated natural RNA modification. Using in vitro selection from random DNA, we developed deoxyribozymes that are sensitive to the presence of N\(^6\)-methyladenosine in RNA near the cleavage site. One class of these DNA enzymes shows faster cleavage of methylated RNA, while others are strongly inhibited by the modified nucleotide. The general applicability of the new deoxyribozymes is demonstrated for several examples of natural RNA sequences, including a lncRNA and a set of C/D box snoRNAs, which have been suggested to contain m\(^6\)A as a regulatory element that influences RNA folding and protein binding.}, language = {en} } @unpublished{PetersenLindnerMitric2018, author = {Petersen, Jens and Lindner, Joachim O. and Mitric, Roland}, title = {Ultrafast Photodynamics of Glucose}, series = {Journal of Physical Chemistry B}, journal = {Journal of Physical Chemistry B}, doi = {10.1021/acs.jpcb.7b08602}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159155}, year = {2018}, abstract = {We have investigated the photodynamics of \(\beta\)-D-glucose employing our field-induced surface hopping method (FISH), which allows us to simulate the coupled electron-nuclear dynamics, including explicitly nonadiabatic effects and light-induced excitation. Our results reveal that from the initially populated S\(_{1}\) and S\(_{2}\) states, glucose returns nonradiatively to the ground state within about 200 fs. This takes place mainly via conical intersections (CIs) whose geometries in most cases involve the elongation of a single O-H bond, while in some instances ring-opening due to dissociation of a C-O bond is observed. Experimentally, excitation to a distinct excited electronic state is improbable due to the presence of a dense manifold of states bearing similar oscillator strengths. Our FISH simulations explicitly including a UV laser pulse of 6.43 eV photon energy reveals that after initial excitation the population is almost equally spread over several close-lying electronic states. This is followed by a fast nonradiative decay on the time scale of 100-200 fs, with the final return to the ground state proceeding via the S\(_{1}\) state through the same types of CIs as observed in the field-free simulations.}, language = {en} } @unpublished{NoseWernerUedaetal.2018, author = {Nose, Naoko and Werner, Rudolf A. and Ueda, Yuichiro and G{\"u}nther, Katharina and Lapa, Constantin and Javadi, Mehrbod S. and Fukushima, Kazuhito and Edenhofer, Frank and Higuchi, Takahiro}, title = {Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay}, series = {International Journal of Cardiology}, journal = {International Journal of Cardiology}, issn = {0167-5273}, doi = {10.1016/j.ijcard.2018.06.089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163320}, year = {2018}, abstract = {Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.}, subject = {Stammzelle}, language = {en} } @unpublished{MuellerDraegerMaetal.2018, author = {M{\"u}ller, Stefan and Draeger, Simon and Ma, Kiaonan and Hensen, Matthias and Kenneweg, Tristan and Pfeiffer, Walter and Brixner, Tobias}, title = {Fluorescence-Detected Two-Quantum and One-Quantum-Two-Quantum 2D Electronic Spectroscopy}, series = {Journal of Physical Chemistry Letters}, journal = {Journal of Physical Chemistry Letters}, doi = {10.1021/acs.jpclett.8b00541}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173468}, year = {2018}, abstract = {We demonstrate two-quantum (2Q) coherent two-dimensional (2D)electronic spectroscopy using a shot-to-shot-modulated pulse shaper and fluorescence detection. Broadband collinear excitation is realized with the supercontinuum output of an argon-filled hollow-core fiber, enabling us to excite multiple transitions simultaneously in the visible range. The 2Q contribution is extracted via a three-pulse sequence with 16-fold phase cycling and simulated employing cresyl violet as a model system. Furthermore, we report the first experimental realization of one-quantum-two-quantum (1Q-2Q) 2D spectroscopy, offering less congested spectra as compared with the 2Q implementation. We avoid scattering artifacts and nonresonant solvent contributions by using fluorescence as the observable. This allows us to extract quantitative information about doubly excited states that agree with literature expectations. The high sensitivity and background-free nature of fluorescence detection allow for a general applicability of this method to many other systems.}, subject = {Fluoreszenz}, language = {en} } @unpublished{LoefflerMayerTrujilloVieraetal.2018, author = {L{\"o}ffler, Mona C. and Mayer, Alexander E. and Trujillo Viera, Jonathan and Loza Valdes, Angel and El-Merahib, Rabih and Ade, Carsten P. and Karwen, Till and Schmitz, Werner and Slotta, Anja and Erk, Manuela and Janaki-Raman, Sudha and Matesanz, Nuria and Torres, Jorge L. and Marcos, Miguel and Sabio, Guadalupe and Eilers, Martin and Schulze, Almut and Sumara, Grzegorz}, title = {Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity}, series = {The EMBO Journal}, journal = {The EMBO Journal}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176093}, year = {2018}, abstract = {Nutrient overload in combination with decreased energy dissipation promotes obesity and diabetes. Obesity results in a hormonal imbalance, which among others, activates G-protein coupled receptors utilizing diacylglycerol (DAG) as secondary messenger. Protein kinase D1 (PKD1) is a DAG effector which integrates multiple nutritional and hormonal inputs, but its physiological role in adipocytes is unknown. Here, we show that PKD1 promotes lipogenesis and suppresses mitochondrial fragmentation, biogenesis, respiration, and energy dissipation in an AMP-activated protein kinase (AMPK)-dependent manner. Moreover, mice lacking PKD1 in adipocytes are resistant to diet-induced obesity due to elevated energy expenditure. Beiging of adipocytes promotes energy expenditure and counteracts obesity. Consistently, deletion of PKD1 promotes expression of the β3-adrenergic receptor (ADRB3) in a CCAAT/enhancerbinding protein (C/EBP)-α and δ-dependent manner, which leads to the elevated expression of beige markers in adipocytes and subcutaneous adipose tissue. Finally, deletion of PKD1 in adipocytes improves insulin sensitivity and ameliorates liver steatosis. Thus, loss of PKD1 in adipocytes increases energy dissipation by several complementary mechanisms and might represent an attractive strategy to treat obesity and its related complications.}, language = {en} } @unpublished{HoebartnerSteinmetzgerPalanisamyetal.2018, author = {H{\"o}bartner, Claudia and Steinmetzger, Christian and Palanisamy, Navaneethan and Gore, Kiran R.}, title = {A multicolor large Stokes shift fluorogen-activating RNA aptamer with cationic chromophores}, series = {Chemistry - A European Journal}, journal = {Chemistry - A European Journal}, doi = {https://doi.org/10.1002/chem.201805882}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174197}, year = {2018}, abstract = {Large Stokes shift (LSS) fluorescent proteins (FPs) exploit excited state proton transfer pathways to enable fluorescence emission from the phenolate intermediate of their internal 4 hydroxybenzylidene imidazolone (HBI) chromophore. An RNA aptamer named Chili mimics LSS FPs by inducing highly Stokes-shifted emission from several new green and red HBI analogs that are non-fluorescent when free in solution. The ligands are bound by the RNA in their protonated phenol form and feature a cationic aromatic side chain for increased RNA affinity and reduced magnesium dependence. In combination with oxidative functional-ization at the C2 position of the imidazolone, this strategy yielded DMHBO\(^+\), which binds to the Chili aptamer with a low-nanomolar K\(_D\). Because of its highly red-shifted fluorescence emission at 592 nm, the Chili-DMHBO\(^+\) complex is an ideal fluorescence donor for F{\"o}rster resonance energy transfer (FRET) to the rhodamine dye Atto 590 and will therefore find applications in FRET-based analytical RNA systems.}, language = {en} } @unpublished{HermannCidMattocketal.2018, author = {Hermann, Alexander and Cid, Jessica and Mattock, James D. and Dewhurst, Rian D. and Krummenacher, Ivo and Vargas, Alfredo and Ingleson, Michael J. and Braunschweig, Holger}, title = {Diboryldiborenes: π-Conjugated B\(_4\) Chains Isoelectronic to the Butadiene Dication}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201805394}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167977}, year = {2018}, abstract = {sp\(^2\)-sp\(^3\) diborane species based on bis(catecholato)diboron and N-heterocyclic carbenes (NHCs) are subjected to catechol/bromide exchange selectively at the sp\(^3\) boron atom. The reduction of the resulting 1,1-dibromodiborane adducts led to reductive coupling and isolation of doubly NHC-stabilized 1,2-diboryldiborenes. These compounds are the first examples of molecules exhibiting pelectron delocalization over an all-boron chain.}, language = {en} } @unpublished{CidHermannRadcliffeetal.2018, author = {Cid, Jessica and Hermann, Alexander and Radcliffe, James E. and Curless, Liam D. and Braunschweig, Holger and Ingleson, Michael J.}, title = {Synthesis of Unsymmetrical Diboron(5) Compounds and Their Conversion to Diboron(5) Cations}, series = {Organometallics}, journal = {Organometallics}, doi = {10.1021/acs.organomet.8b00288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164299}, year = {2018}, abstract = {Reaction of bis-catecholatodiboron-NHC adducts, B\(_2\)Cat\(_2\)(NHC), (NHC = IMe (tetramethylimidazol-2-ylidene), IMes (1,3-dimesitylimidazol-2-ylidene) or IDIPP (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)) with BCl3 results in the replacement of the catecholato group bound to the four coordinate boron with two chlorides to yield diboron(5) Lewis acid-base adducts of formula CatB-BCl\(_2\)(NHC). These compounds are precursors to diboron(5) monocations, accessed by adding AlCl\(_3\) or K[B(C\(_6\)F\(_5\))\(_4\)] as halide abstraction agents in the presence of a Lewis base. The substitution of the chlorides of CatB-BCl\(_2\)(NHC) for hydrides is achieved using Bu\(_3\)SnH and a halide abstracting agent to form 1,1-dihydrodiboron(5) compounds, CatB-BH\(_2\)(NHC). Attempts to generate diboron(4) monocations of formula [CatB-B(Y)(NHC)]\(^+\) (Y = Cl or H) led to the rapid formation of CatBY.}, language = {en} } @unpublished{BoehnkeDellermannCeliketal.2018, author = {B{\"o}hnke, Julian and Dellermann, Theresa and Celik, Mehmet Ali and Krummenacher, Ivo and Dewhurst, Rian D. and Demeshko, Serhiy and Ewing, William C. and Hammond, Kai and Heß, Merlin and Bill, Eckhard and Welz, Eileen and R{\"o}hr, Merle I. S. and Mitric, Roland and Engels, Bernd and Meyer, Franc and Braunschweig, Holger}, title = {Isolation of diradical products of twisted double bonds}, series = {Nature Communications}, journal = {Nature Communications}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-160248}, year = {2018}, abstract = {Molecules containing multiple bonds between atoms—most often in the form of olefins—are ubiquitous in nature, commerce, and science, and as such have a huge impact on everyday life. Given their prominence, over the last few decades, frequent attempts have been made to perturb the structure and reactivity of multiply-bound species through bending and twisting. However, only modest success has been achieved in the quest to completely twist double bonds in order to homolytically cleave the associated π bond. Here, we present the isolation of double-bond-containing species based on boron, as well as their fully twisted diradical congeners, by the incorporation of attached groups with different electronic properties. The compounds comprise a structurally authenticated set of diamagnetic multiply-bound and diradical singly-bound congeners of the same class of compound.}, language = {en} } @unpublished{BoehnkeBraunschweigJimenezHallaetal.2018, author = {B{\"o}hnke, Julian and Braunschweig, Holger and Jim{\´e}nez-Halla, Oscar and Krummenacher, Ivo and Stennett, Tom E.}, title = {Half-Sandwich Complexes of an Extremely Electron-Donating, Re-dox-Active η\(^6\)-Diborabenzene Ligand}, series = {Journal of the American Chemical Society}, journal = {Journal of the American Chemical Society}, doi = {10.1021/jacs.7b12394}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156766}, year = {2018}, abstract = {The heteroarene 1,4-bis(CAAC)-1,4-diborabenzene (1; CAAC = cyclic (alkyl)(amino)carbene) reacts with [(MeCN)\(_3\)M(CO)\(_3\)] (M = Cr, Mo, W) to yield half-sandwich complexes of the form [(η\(^6\)-diborabenzene)M(CO)\(_3\)] (M = Cr (2), Mo (3), W (4)). Investigation of the new complexes with a combination of X-ray diffraction, spectroscopic methods and DFT calculations shows that ligand 1 is a remarkably strong electron donor. In particular, [(η\(^6\)-arene)M(CO)\(_3\)] complexes of this ligand display the lowest CO stretching frequencies yet observed for this class of complex. Cyclic voltammetry on complexes 2-4 revealed one reversi- ble oxidation and two reversible reduction events in each case, with no evidence of ring-slippage of the arene to the η\(^4\) binding mode. Treatment of 4 with lithium metal in THF led to identification of the paramagnetic complex [(1)W(CO)\(_3\)]Li·2THF (5). Compound 1 can also be reduced in the absence of a transition metal to its dianion 1\(^{2-}\), which possesses a quinoid-type structure.}, language = {en} } @unpublished{BoehnkeArrowsmithBraunschweig2018, author = {B{\"o}hnke, Julian and Arrowsmith, Merle and Braunschweig, Holger}, title = {Activation of a Zerovalent Diboron Compound by Desymmetrization}, series = {Journal of the American Chemical Society}, journal = {Journal of the American Chemical Society}, doi = {10.1021/jacs.8b06930}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167983}, year = {2018}, abstract = {The desymmetrization of the cyclic (alkyl)(amino)carbene-supported diboracumulene, B\(_2\)(cAAC\(^{Me}\))\(_2\) (cAAC\(^{Me}\) = 1- (2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) by mono-adduct formation with IMe\(^{Me}\) (1,3-dimethylimidazol-2-ylidene) yields the zerovalent sp-sp\(^2\) diboron compound B\(_2\)(cAAC\(^{Me}\))\(_2\)(IMe\(^{Me}\)), which provides a versatile platform for the synthesis of novel symmetrical and unsymmetrical zerovalent sp\(^2\)-sp\(^2\) diboron compounds by adduct formation with IMe\(^{Me}\) and CO, respectively. Furthermore, B\(_2\)(cAAC\(^{Me}\))\(_2\)(IMe\(^{Me}\)) displays enhanced reactivity compared to its symmetrical precursor, undergoing spontaneous intramolecular C-H activation and facile twofold hydrogenation, the latter resulting in B-B bond cleavage and the formation of the mixed-base parent borylene, (cAAC\(^{Me}\))(IMe\(^{Me}\))BH.}, language = {en} }