Inside Cover: Structural and Mechanistic Studies on Substrate and Stereoselectivity of the Indole Monooxygenase VpIndA1: New Avenues for Biocatalytic Epoxidations and Sulfoxidations (Angew. Chem. Int. Ed. 17/2023)

Flavoprotein monooxygenases are a versatile group of enzymes for biocatalytic transformations. Among these, group E monooxygenases (GEMs) catalyze enantioselective epoxidation and sulfoxidation reactions. Here, we describe the crystal structure of an indole monooxygenase from the bacterium Variovorax paradoxus EPS, a GEM designated as VpIndA1. Complex structures with substrates reveal productive binding modes that, in conjunction with force-field calculations and rapid mixing kinetics, reveal the structural basis of substrate and stereoselectivity. Structure-based redesign of the substrate cavity yielded variants with new substrate selectivity (for sulfoxidation of benzyl phenyl sulfide) or with greatly enhanced stereoselectivity (from 35.1 % to 99.8 % ee for production of (1S,2R)-indene oxide). This first determination of the substrate binding mode of GEMs combined with structure-function relationships opens the door for structure-based design of these powerful biocatalysts.     

Experimental and Theoretical Structure Elucidation of the [2 : 1] Complex Ion of Carbo[n]helicene with n=6, 7 and 8 and Ag+

Gas-phase complexes of [n]helicenes with n=6, 7 and 8 and the silver(I) cation are generated utilizing electrospray ionization mass spectrometry (ESI-MS). Besides the well-established [1 : 1] helicene/Ag⁺-complex in which the helicene provides a tweezer-like surrounding for the Ag⁺, there is also a [2 : 1] complex formed. Density functional theory (DFT) calculations in conjunction with energy-resolved collision-induced dissociation (ER-CID) experiments reveal that the second helicene attaches via π-π stacking to the first helicene, which is part of the pre-formed [1 : 1] tweezer complex with Ag⁺. For polycyclic aromatic hydrocarbons (PAHs) of planar structure, the [2 : 1] complex with silver(I) is typically structured as an Ag⁺-bound dimer in which the Ag⁺ would bind to both PAHs as the central metal ion (PAH–Ag⁺–PAH). For helicenes, the Ag⁺-bound dimer is of similar thermochemical stability as the π-π stacked dimer, however, it is kinetically inaccessible. Coronene (Cor) is investigated in comparison to the helicenes as an essentially planar PAH. In analogy to the π-π stacked dimer of the helicenes, the Cor−Ag⁺−Cor−Cor complex is also observed. Competition experiments using [n]helicene mixtures reveal that the tweezer complexes of Ag⁺ are preferably formed with the larger helicenes, with n=6 being entirely ignored as the host for Ag⁺ in the presence of n=7 or 8.     

CycloSiFA: The Next Generation of Silicon-Based Fluoride Acceptors for Positron Emission Tomography (PET)

The ring-opening Si-fluorination of a variety of azasilole derivatives cyclo-1-(iPr₂Si)−4-X−C₆H₃−2-CH₂NR ( 4 : R=2,6-iPr₂C₆H₃, X=H; 4 a : R=2,4,6-Me₃C₆H₂, X=H; 9 : R=2,6-iPr₂C₆H₃, X=tBuMe₂SiO; 10 : R=2,6-iPr₂C₆H₃, X=OH; 13 : R=2,6-iPr₂C₆H₃, X=HCCCH₂O; 22 : R=2,6-iPr₂C₆H₃, X=tBuMe₂SiCH₂O) with different ¹⁹F-fluoride sources was studied, optimized and the experience gained was used in a translational approach to create a straightforward ¹⁸F-labelling protocol for the azasilole derivatives [¹⁸F] 6 and [¹⁸F] 14 . The latter constitutes a potential clickable CycloSiFA prosthetic group which might be used in PET tracer development using Cu-catalysed triazole formation. Based on our findings, CycloSiFA has the potential to become a new entry into non-canonical labelling methodologies for radioactive PET tracer development.     

Determination of ethaverine and papaverine using ion-selective electrodes.

Ion-selective poly(vinyl chloride) membrane electrodes for the opium alkaloids papaverine and ethaverine are presented. The electrode membranes contain ion pairs of the alkaloids with the anionic counter ion tetraphenylborate. The detection limits for all electrodes were approximately 2 x 10(-6) mol dm-3 at pH 5.0 in 100 mmol dm-3 buffered solutions and the measured slopes were close to the values theoretically expected. The selectivity coefficient observed for the ethaverine-tetraphenylborate electrode is 10(-1.1) with respect to papaverine. The suitability of the membranes for single-use electrodes is discussed.     

Pyridazines. LIX. Synthesis of c-annelated pyridazines from 3-amino-4-pyridazinecarbonitrile

The utility of the aminonitrile 1 as an educt for the preparation of several new examples of heterocyclefused pyridazines (the [1,2,4]triazolo[1′,5′:1,6]pyrimido[4,5-c]pyridazine 7 , the pyrimido[4,5-c]pyridazines 8, 10a,b , and the pyrido[2,3-c]pyridazine 11 ) is demonstrated.     

A New Strategy for the Synthesis of alpha-Difluoromethyl-Substituted alpha-Hydroxy and alpha-Amino Acids

A new method for the preparation of alpha-chlorodifluoromethyl-, alpha-bromodifluoromethyl-, and alpha-difluoromethyl-substituted alpha-hydroxy and alpha-amino acid esters 11, 19-21 is described. The key step of the synthesis is the regioselective alkylation of ketones 5, 7-9 and imines 16-18 with C-nucleophiles. The ketones 7-9 are readily available from 3,3,3-trifluorolactate 1 by a five-step procedure. Subsequent removal of the protecting groups from 19-21 provides the corresponding free amino acids 25, 26, 28.     

Reconstitution of apomyoglobin with bile pigments

Summary Apomyoglobin was reconstituted with bile pigments of the verdinoid, 2,3-dihydroverdinoid, pterobilinoid, and violinoid type. Absorption and circular dichroism data as well as formation constants of the complexes were measured. From these results it was concluded that chromophore binding and induced chirality of these pigments are mainly governed by a lipophilic region opposite to the propionic side chain(s) and the asymmetric position of the hydrogen bonding acceptors of the propionic acid side chain(s) at the entrance of the protein pocket.Dedicated to Prof. Dr. A. Eschenmoser on occasion of his 65th birthday     

Extrem aufgeweitete Tetrathiafulvalene mit Polyen-Spacern. Carotinoide Tetrathiafulvalene. Polymethin-tetracyanotetrathiafulvalen-Radikalkationen,eine neue Klasse von Violenen

Extremely Expanded Tetrathiafulvalenes with Polyene Spacers. Carotinoid Tetrathiafulvalenes. Polymethin-Tetracyanotetrathiafulvalene Radical Cations, a New Class of Violenes The synthesis of extended tetrathiafulvalenes 11 with di-, tetra-, hexa-, octa-, deca- and dodecamethine spacers is described by a PPh₃-induced Wittig-reaction-like condensation of the corresponding polyenedials 10 with 2-thio-1,3-dithiole-4,5-dicarbonitrile ( 9 ). By the same procedure, the dimethyloctamethine- and the tetramethyl-hexadecamethine-tetrathiafulvalenes 14 and 15 , respectively, were obtained. The extended tetrathiafulvalenes represent multistep vinylogous redox systems of the ‘violene type’. They can be oxidized to give the cyanine-like radical cations, e.g. 11 _sem, 14 _sem, and 15 _sem, and the dications, e.g. 11 _ox, 14 _ox, and 15 _ox; their UV/VIS/NIR spectra are reported. The crystal and molecular structure of (all-E)-2,2′-(octa-2,4,6-trien-1,8-diylidene)bis[1,3-dithiole-4,5-dicarbonitrile] ( 11e ) was determined: it is a rod-like, planar molecule; in the crystal, it forms staples along the longest molecule axis. The CV measurements confirm that the redox potentials of 11, 14 , and 15 decrease asymptotically with the increasing length of the spacer. Because of the close relationship of the extended tetrathiafulvalenes (ETTF's) to the carotinoids, they are named ‘caroviologenes’; they formally belong to the class of molecular wires.     

Determination of boron and hydrogen in materials for multicrystalline solar cell production with prompt gamma activation analysis

Journal of Radioanalytical and Nuclear Chemistry - For the optimization of the manufacturing process of multicrystalline silicon (mc-Si) for solar cells in order to reduce energy consumption and...