TY  - JOUR
A1  - Wohlfart, Jonas
A1  - Holzgrabe, Ulrike
T1  - Analysis of histamine and sisomicin in gentamicin: search for the causative agents of adverse effects
JF  - Archiv der Pharmazie
N2  - In 1998, the aminoglycoside antibiotic gentamicin sulfate caused several cases of deaths in the United States, after the switch from twice- to once-daily application. Endotoxins were discussed as the cause for the adverse effects and sisomicin was identified as the lead impurity; batches containing sisomicin were contaminated with more impurities and were responsible for the fatalities. In 2016, anaphylactic reactions in horses, and later in humans with one fatality, were observed after application of gentamicin sulfate contaminated with histamine. To determine whether histamine was responsible for the 1990s death cases as well, histamine was quantified by means of liquid chromatography–tandem mass spectrometry (LC-MS/MS) in 30 samples of gentamicin sulfate analyzed in previous studies. Furthermore, a relative quantification of sisomicin was performed to check for a correlation between histamine and the lead impurity. A maximum amount of 11.52 ppm histamine was detected, which is below the limit for anaphylactic reactions of 16 ppm, and no correlation of the two impurities was observed. However, the European Medicines Agency recommends a stricter limit with regard to the maximum single dose of gentamicin sulfate to reach a greater gap between the maximum histamine exposition of 4.3 µg and the quantity known to cause hypotension of 7 µg. The low amounts of histamine and the fact that there is no connection with the contamination with sisomicin showed that histamine was not the cause for the death cases in the United States in 1998, and endotoxins remain the most probable explanation.
KW  - chemistry
KW  - sisomicin
KW  - drug impurities
KW  - gentamicin sulfate
KW  - histamine
KW  - LC-MS/MS
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256596
VL  - 354
IS  - 12
ER  - 
TY  - JOUR
A1  - Wirthensohn, Raphael
A1  - Finze, Maik
T1  - The crystal structure of trimethylsulfonium tris(trifluoromethylsulfonyl)methanide, C\(_7\)H\(_9\)F\(_9\)O\(_6\)S\(_4\)
JF  - Zeitschrift für Kristallographie - New Crystal Structures
N2  - C\(_7\)H\(_9\)F\(_9\)O\(_6\)S\(_4\), orthorhombic, P2\(_1\)2\(_1\)2\(_1\) (no. 19), a = 8.80180(10) Å, b= 10.96580(10) Å, c = 16.91360(10) Å,V= 1632.48(3) Å\(^3\), Z= 4, R\(_{gt}\)(F) = 0.0222, wR\(_{ref}\)(F\(^2\)) = 0.0604, T = 100 K.
KW  - chemistry
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231358
VL  - 236
IS  - 2
ER  - 
TY  - JOUR
A1  - Schmidt, Paul
A1  - Fantuzzi, Felipe
A1  - Klopf, Jonas
A1  - Schröder, Niklas B.
A1  - Dewhurst, Rian D.
A1  - Braunschweig, Holger
A1  - Engel, Volker
A1  - Engels, Bernd
T1  - Twisting versus delocalization in CAAC- and NHC-stabilized boron-based biradicals: the roles of sterics and electronics
JF  - Chemistry - A European Journal
N2  - Twisted boron-based biradicals featuring unsaturated C\(_2\)R\(_2\) (R=Et, Me) bridges and stabilization by cyclic (alkyl)(amino)carbenes (CAACs) were recently prepared. These species show remarkable geometrical and electronic differences with respect to their unbridged counterparts. Herein, a thorough computational investigation on the origin of their distinct electrostructural properties is performed. It is shown that steric effects are mostly responsible for the preference for twisted over planar structures. The ground-state multiplicity of the twisted structure is modulated by the σ framework of the bridge, and different R groups lead to distinct multiplicities. In line with the experimental data, a planar structure driven by delocalization effects is observed as global minimum for R=H. The synthetic elusiveness of C\(_2\)R\(_2\)-bridged systems featuring N-heterocyclic carbenes (NHCs) was also investigated. These results could contribute to the engineering of novel main group biradicals.
KW  - chemistry
KW  - radicals
KW  - ab initio calculations
KW  - boron
KW  - carbene ligands
KW  - density functional calculations
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256636
VL  - 27
IS  - 16
ER  - 
TY  - JOUR
A1  - Otto, Christoph
A1  - Friedrich, Alexandra
A1  - Madunić, Ivana Vrhovac
A1  - Baumeier, Christian
A1  - Schwenk, Robert W.
A1  - Karaica, Dean
A1  - Germer, Christoph-Thomas
A1  - Schürmann, Annette
A1  - Sabolić, Ivan
A1  - Koepsell, Hermann, Hermann
T1  - Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na\(^+\)-D-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine
JF  - ACS Omega
N2  - In enterocytes, protein RS1 (RSC1A1) mediates an increase of glucose absorption after ingestion of glucose-rich food via upregulation of Na+-D-glucose cotransporter SGLT1 in the brush-border membrane (BBM). Whereas RS1 decelerates the exocytotic pathway of vesicles containing SGLT1 at low glucose levels between meals, RS1-mediated deceleration is relieved after ingestion of glucose-rich food. Regulation of SGLT1 is mediated by RS1 domain RS1-Reg, in which Gln-Ser-Pro (QSP) is effective. In contrast to QSP and RS1-Reg, Gln-Glu-Pro (QEP) and RS1-Reg with a serine to glutamate exchange in the QSP motif downregulate the abundance of SGLT1 in the BBM at high intracellular glucose concentrations by about 50%. We investigated whether oral application of QEP improves diabetes in db/db mice and affects the induction of diabetes in New Zealand obese (NZO) mice under glucolipotoxic conditions. After 6-day administration of drinking water containing 5 mM QEP to db/db mice, fasting glucose was decreased, increase of blood glucose in the oral glucose tolerance test was blunted, and insulin sensitivity was increased. When QEP was added for several days to a high fat/high carbohydrate diet that induced diabetes in NZO mice, the increase of random plasma glucose was prevented, accompanied by lower plasma insulin levels. QEP is considered a lead compound for development of new antidiabetic drugs with more rapid cellular uptake. In contrast to SGLT1 inhibitors, QEP-based drugs may be applied in combination with insulin for the treatment of type 1 and type 2 diabetes, decreasing the required insulin amount, and thereby may reduce the risk of hypoglycemia.
KW  - chemistry
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230654
N1  - Lizenz: https://pubs.acs.org/page/policy/authorchoice_termsofuse.html
VL  - 5
IS  - 45
ER  - 
TY  - JOUR
A1  - Mufusama, Jean-Pierre
A1  - Feineis, Doris
A1  - Mudogo, Virima
A1  - Kaiser, Marcel
A1  - Brun, Reto
A1  - Bringmann, Gerhard
T1  - Antiprotozoal dimeric naphthylisoquinolines, mbandakamines B\(_3\) and B\(_4\), and related 5,8′-coupled monomeric alkaloids, ikelacongolines A–D, from a Congolese Ancistrocladus liana
JF  - RSC Advances
N2  - From the leaves of a botanically and phytochemically as yet unexplored Ancistrocladus liana discovered in the rainforests of the Central region of the Democratic Republic of the Congo in the vicinity of the town of Ikela, six new naphthylisoquinoline alkaloids were isolated, viz., two constitutionally unsymmetric dimers, the mbandakamines B\(_3\) (3) and B\(_4\) (4), and four related 5,8′-linked monomeric alkaloids, named ikelacongolines A–D (5a, 5b, 6, and 7). The dimers 3 and 4 are structurally unusual quateraryls comprising two 5,8′-coupled monomers linked via a sterically strongly constrained 6′,1′′-connection between their naphthalene units. These compounds contain seven elements of chirality, four stereogenic centers and three consecutive chiral axes. They were identified along with two known related compounds, the mbandakamines A (1) and B\(_2\) (2), which had so far only been detected in two Ancistrocladus species indigenous to the Northwestern Congo Basin. In addition, five known monomeric alkaloids, previously found in related Central African Ancistrocladus species, were isolated from the here investigated Congolese liana, three of them belonging to the subclass of 5,8′-coupled naphthylisoquinoline alkaloids, whereas two compounds exhibited a less frequently occurring 7,8′-biaryl linkage. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR), chemical (oxidative degradation), and chiroptical (electronic circular dichroism) methods. The mbandakamines B\(_3\) (3) and B\(_4\) (4) displayed pronounced activities in vitro against the malaria parasite Plasmodium falciparum and the pathogen of African sleeping sickness, Trypanosoma brucei rhodesiense.
KW  - chemistry
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201141
VL  - 9
IS  - 21
ER  - 
TY  - JOUR
A1  - Kraft, Andreas
A1  - Stangl, Johannes
A1  - Krause, Ana-Maria
A1  - Müller-Buschbaum, Klaus
A1  - Beuerle, Florian
T1  - Supramolecular frameworks based on [60]fullerene hexakisadducts
JF  - Beilstein Journal of Organic Chemistry
N2  - [60]Fullerene hexakisadducts possessing 12 carboxylic acid side chains form crystalline hydrogen-bonding frameworks in the solid state. Depending on the length of the linker between the reactive sites and the malonate units, the distance of the [60]fullerene nodes and thereby the spacing of the frameworks can be controlled and for the most elongated derivative, continuous channels are obtained within the structure. Stability, structural integrity and porosity of the material were investigated by powder X-ray diffraction, thermogravimetry and sorption measurements.
KW  - chemistry
KW  - fullerenes
KW  - hexakisadducts
KW  - hydrogen bonding
KW  - porous materials
KW  - structure elucidation
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171996
VL  - 13
ER  - 
TY  - JOUR
A1  - Koch, Oliver
A1  - Cappel, Daniel
A1  - Nocker, Monika
A1  - Jaeger, Timo
A1  - Flohé, Leopold
A1  - Sotriffer, Christoph
A1  - Selzer, Paul
T1  - Virtual screening using structure-based consensus pharmacophore models and ensemble docking based on MD-generated conformations : [From 6th German Conference on Chemoinformatics, GCC 2010, Goslar, Germany. 7-9 November 2010]
JF  - Journal of Cheminformatics
N2  - No abstract available.
KW  - chemistry
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142830
VL  - 3
IS  - Suppl. 1
ER  - 
TY  - THES
A1  - Herok, Christoph
T1  - Quantum Chemical Exploration of Potential Energy Surfaces: Reaction Cycles and Luminescence Phenomena
T1  - Quantenchemische Erforschung von Energiehyperflächen: Reaktionszyklen und Lumineszenzphänomene
N2  - This work aims at elucidating chemical processes involving homogeneous catalysis and photo–physical relaxation of excited molecules in the solid state. Furthermore, compounds with supposedly small singlet–triplet gaps and therefore biradicaloid character are investigated with respect to their electro–chemical behavior. The work on hydroboration catalysis via a reduced 9,10–diboraanthracene (DBA) was preformed in collaboration with the Wagner group in Frankfurt, more specifically Dr. Sven Prey, who performed all laboratory experiments. The investigation of delayed luminescence properties in arylboronic esters in their solid state was conducted in collaboration with the Marder group in Würzburg. The author of this work took part in the synthesis of the investigated compounds while being supervised by Dr. Zhu Wu. The final project was a collaboration with the group of Anukul Jana from Hyderabad, India who provided the experimental data.
N2  - Ziel dieser Arbeit ist die Aufklärung chemischer Prozesse, die homogene Katalyse und photophysikalische Relaxation angeregter Moleküle im Festkörper beinhalten. Darüber hinaus werden Verbindungen mit vermeintlich kleinen Singulett-Triplett-Lücken und damit biradikaloidem Charakter auf ihr elektrochemisches Verhalten hin untersucht. Die Arbeiten zur Hydroborierungskatalyse mit einem reduzierten 9,10-Diboraanthracen (DBA) wurden in Zusammenarbeit mit der Wagner-Gruppe in Frankfurt durchgeführt, genauer gesagt mit Dr. Sven Prey, der alle Laborexperimente durchführte. Die Untersuchung der verzögerten Lumineszenzeigenschaften von Arylborsäureestern im Festkörper wurde in Zusammenarbeit mit der Marder Gruppe in Würzburg durchgeführt. Der Autor dieser Arbeit war an der Synthese der untersuchten Verbindungen beteiligt und wurde dabei von Dr. Zhu Wu betreut. Das abschließende Projekt war eine Zusammenarbeit mit der Gruppe von Anukul Jana aus Hyderabad, Indien, die die experimentellen Daten zur Verfügung stellte.
KW  - Simulation
KW  - Quantum Chemistry
KW  - Reaction Mechanism
KW  - Fluorescence
KW  - Phosphoresence
KW  - Chemie
KW  - Katalyse
KW  - Lumineszenz
KW  - chemistry
KW  - simulation
KW  - catalysis
KW  - mechanism
KW  - luminescence
KW  - Energiehyperfläche
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-352185
ER  - 
TY  - JOUR
A1  - Hartung, Andreas
A1  - Seufert, Florian
A1  - Berges, Carsten
A1  - Gessner, Viktoria H.
A1  - Holzgrabe, Ulrike
T1  - One-Pot Ugi/Aza-Michael Synthesis of Highly Substituted 2,5-Diketopiperazines with Anti-Proliferative Properties
JF  - Molecules
N2  - The well-known Ugi reaction of aldehydes with amines, carboxylic acids and isocyanides leads to the formation of acyclic alpha-acylaminocarboxamides. Replacement of the carboxylic acid derivatives with beta-acyl substituted acrylic acids gives access to highly substituted 2,5-diketopiperazines in one single reaction-step without additives or complex reaction procedures. The obtained diketopiperazines show anti-proliferative effects on activated T cells and represent therefore potential candidates for targeting unwanted T cell-mediated immune responses.
KW  - multicomponent Ugi-type reaction
KW  - intramolecular Michael addition
KW  - strategy
KW  - derivates
KW  - diketopiperazines
KW  - chemistry
KW  - T cell
KW  - 2,5-diketopiperazines
KW  - anti-proliferative effects
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130423
VL  - 17
IS  - 12
ER  - 
TY  - JOUR
A1  - Hanft, Anna
A1  - Lichtenberg, Crispin
T1  - Dimerization of 2-[(2-((2-aminophenyl)thio)phenyl)amino]-cyclohepta-2,4,6-trien-1-one through hydrogen bonding, C\(_{19}\)H\(_{16}\)N\(_2\)OS
JF  - Zeitschrift für Kristallographie - New Crystal Structures
N2  - C\(_{19}\)H\(_{16}\)N\(_2\)OS, triclinic, P (1) over bar (no. 2), a= 8.1510(3) angstrom, b = 8.8021(3) angstrom, c =11.3953(5) angstrom, alpha =72.546(2)degrees, beta=84.568(2)degrees, gamma =80.760(2)degrees, V =768.86(5) angstrom(3), Z =2, R\(_{gt}\)(F) = 0.0491, WR\(_{ref}\)(F-2) = 0.1494, T =100 K.
KW  - crystal structure
KW  - complexes
KW  - ligands
KW  - tropocoronands
KW  - mononuclear
KW  - chemistry
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229482
VL  - 235
IS  - 4
ER  -