The Site‐Assembly Determines Catalytic Activity of Nanoparticles

Heterogeneous catalysts are often designed as metal nanoparticles supported on oxide surfaces. Here, the relation between particle morphology and reaction kinetics is investigated by scaling relation kinetic Monte Carlo simulations using CO oxidation over Pt nanoparticles as a model reaction. We find that different particle morphologies result in vastly different catalytic activities. The activity is strongly affected by kinetic couplings between sites, and a wide site distribution generally enhances the activity. The present study highlights the role of site‐assemblies as a concept that, in addition to isolated active sites, can be used to understand catalytic reactions over nanoparticles.     

Palladium-catalyzed synthesis of arylamines from aryl halides and lithium bis(trimethylsilyl)amide as an ammonia equivalent

[reaction: see text]. A simple, palladium-catalyzed method to convert aryl halides to the parent anilines using lithium bis(trimethylsilyl)amide (LiN(SiMe3)2) is reported. The reaction is catalyzed by Pd(dba)2 and P(t-Bu)3 and can be run with as little as 0.2 mol % of catalyst. The reaction is faster than competing generation of benzyne intermediates and, therefore, provides the aniline products regiospecifically.     

Cover Picture

The cover picture shows two new catalytic asymmetric reactions in front of an enantiomeric pair of lurs—one of the national symbols of Denmark. Chiral bisoxazoline copper complexes catalyze the reactions. The reaction on the left is the direct enantioselective Mannich reaction of carbonyl compounds with imines to give highly functionalized 4‐oxo‐glutamic esters, while the reaction on the right is the enantioselective nitro‐Mannich reaction of nitro alkanes with imines to give optically active β‐nitro‐α‐amino esters. Why the lur in relation to the present chemistry? Lurs exist as pairs of enantiomers and they probably belong to some of the first man‐made pair of enantiomers, as they are from the Bronze Age (1000–500 BC). The lurs are the oldest musical instruments that can still be played, and are used as enantiomers. Side by side stood two lur‐players, symmetric in every detail, the soft curves of the instruments swaying upwards and outwards at each side. The sonorous notes emphasized the solemn nature of the rituals. It is conceivable that the sound of the lur also accompanied the crackle of the funeral pyre when one of the tribe was cremated and laid to rest in the burial mound of his forefathers. The lurs are made of bronze (copper) and were discovered in lakes; less than 50 are known. The most famous pair of lurs was found in Brudevælte and is the pair shown on the cover. Further information about lurs can be obtained from kaj@chem.au.dk. The picture of the lurs and the accompanying music (click here to listen to the music: www.angewandte.com) are used with permission from The National Museum. For more details about the two new catalytic asymmetric reactions, see Jørgensen et al. on p. 2992 ff. and p. 2995 ff.     

Gapmer Antisense Oligonucleotides Containing 2′,3′-Dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-d-lyxofuranosyl Nucleotides Display Site-Specific RNase H Cleavage and Induce Gene Silencing

Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing.     

Ab initio study of the NMR shielding constants and spin-spin coupling constants in cyclopropene

Summary Ab initio calculations of parameters which characterize the NMR spectrum are presented for the cyclopropene molecule. The London orbitals CHF (or GIAO-CHF, Gauge-Independent Atomic Orbital Coupled Hartree-Fock) results for the shielding constants are in good agreement with the experimental data, accurately determined, and with otherab initio values. The calculations of the NMR spin-spin coupling constants have been performed using the Multiconfiguration Time-Dependent Hartree-Fock (MC TDHF) approach. Different basis sets and MC SCF wavefunctions were used to estimate the accuracy of the results. Good agreement is obtained with the coupling constants estimated using the available experimental data.Dedicated to Professor Werner Kutzelnigg on the occasion of his 60th birthday     

Control of vortex breakdown in a closed cylinder with a rotating lid

The flow within a closed cylinder with a rotating lid is considered as a prototype for fundamental studies of vortex breakdown. Numerical simulations for various parameter values have been carried out to reproduce the known effect of a thin rotating rod positioned along the center axis as well as analyze the influence of local vorticity sources. As expected, the results show that the breakdown bubbles in the steady axisymmetric flow can be affected dramatically, i.e., fully suppressed or significantly enhanced, by rotating the rod. The main contribution of this article is to show that the observed behavior can be explained by the vorticity generated by the rod locally near the rotating lid and near the fixed lid, as analogous behavior is caused by the introduction of local vorticity sources in the flow without a rod. Moreover, we describe the influence on the breakdown bubbles of the vorticity sources by an analytical model. In addition to improving our understanding, this finding should also open the door to other types of flow control devices capable of generating localized vorticity.     

Direct Cu-mediated aromatic 18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 – the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct ¹⁸F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct ¹⁸F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated ¹⁸F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY of ca. 10%, with a molar activity of 134 ± 22 GBq μmol⁻¹ and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

A simple, scalable and reliable direct ¹⁸F-labeling procedure has been developed and applied to obtain a pretargeting tetrazine-based imaging agent with favorable in vivo characteristics.     

A practical electromediated ipso-hydroxylation of aryl and alkyl boronic acids under an air atmosphere

An efficient electromediated aerobic ipso-hydroxylation reaction of aryl and alkyl boronic acids has been developed. Furthermore, mechanistic insight into the role of superoxide anions in this reaction has also been provided based on electrochemical studies and experimental results.     

On the possible catalysis by single water molecules of gas-phase hydrogen abstraction reactions by OH radicals

The gas phase hydrogen abstraction reaction between OH and CY(2)XH, where X = H, F, OH, or NH(2) and Y = H, CH(3) or F, in the absence and presence of a single water molecule is investigated using both density function theory, B3LYP, and explicitly correlated coupled cluster theory, CCSD(T)-F12. We find that a single water molecule could have a catalytic effect at low temperatures possible in laboratory experiments, but does not seem to catalyze these reactions at 298 K, and will not play a role under relevant atmospheric conditions.