Atroposelective PIII/PV=O Redox Catalysis for the Isoquinoline-Forming Staudinger–aza-Wittig Reaction

Herein, we describe the feasibility of atroposelective P^III/P^V=O redox organocatalysis by the Staudinger–aza-Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co-catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N-oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration.     

Thermal decomposition of trimethylgallium Ga(CH3)3: a shock-tube study and first-principles calculations

The thermal decomposition of Ga(CH3)3 has been studied both experimentally in shock-heated gases and theoretically within an ab-initio framework. Experiments for pressures ranging from 0.3 to 4 bar were performed in a shock tube equipped with atomic resonance absorption spectroscopy (ARAS) for Ga atoms at 403.3 nm. Time-resolved measurements of Ga atom concentrations were conducted behind incident waves as well as behind reflected shock waves at temperatures between 1210 and 1630 K. The temporal variation in Ga-atom concentration was described by a reaction mechanism involving the successive abstraction of methyl radicals from Ga(CH3)3 (R1), Ga(CH3)2 (R2), and GaCH3 (R3), respectively, where the last reaction is the rate-limiting step leading to Ga-atom formation. The rate constant of this reaction (R3) was deduced from a simulation of the measured Ga-atom concentration profiles using thermochemical data from ab-initio calculations for the reactions R1 and R2 as input. The Rice-Ramsperger-Kassel-Marcus (RRKM) method including variational transition state theory was applied for reaction R3 assuming a loose transition state. Structural parameters and vibrational frequencies of the reactant and transition state required for the RRKM calculations were obtained from first-principles simulations. The energy barrier E3(0) of reaction R3, which is the most sensitive parameter in the calculation, was adjusted until the RRKM rate constant matched the experimental one and was found to be E(0) = 288 kJ/mol. This value is in a good agreement with the corresponding ab-initio value of 266 kJ/mol. The rate constant of reaction R3 was found to be k 3/(cm(3) mol(-1)s(-1)) = 2.34 x 10(11) exp[-23330(K/ T)].     

Ab initio molecular dynamics simulation of a medium-sized water cluster anion: from an interior to a surface-located excess electron via a delocalized state

We present a computational study of the structure and dynamics of an excess electron in a medium-sized water cluster aimed at addressing the question of interior vs exterior solvation. Ab initio Born-Oppenheimer molecular dynamics simulations were performed within the DFT framework, employing a hybrid Gaussian and plane-wave formalism together with the PBE exchange-correlation functional and norm-conserving pseudopotentials. Analysis of a 15-ps trajectory allowed us to reach the following conclusions: (i) the excess electron is predominantly located at the cluster surface (even if it is initially placed in the interior), (ii) the computed electron binding energies correlate with the electron localization rather than with its bulk vs surface location, and (iii) a dynamical interconversion between two different H-bond patterns around the electron occurs. The computed electron binding energies and the most relevant features of the IR spectrum are in a very good agreement with results of previous experimental studies.     

Metallization of a thiol-terminated organic surface using chemical vapor deposition

The deposition and the subsequent decomposition of an organometallic precursor, (eta (3)-allyl)(eta (5)-cyclopentadienyl)palladium [Cp(allyl)Pd], on an organic surface exposed by self-assembled monolayers (SAM) was studied using X-ray photoelectron spectroscopy (XPS) and infrared reflection absorption spectroscopy (IRRAS). The interfacial chemical reactions of the vapor-deposited metal precursor with the pendant thiol group of the SAMs made from oligophenyldithiols, which are either prepared directly (terphenyldimethyldithiol, TPDMT) or by a deprotection route from SAMs formed by a monoacylated derivative of biphenyldimethyldithiol (dep. BPDMAc-1) have been studied in detail. When the TPDMT-SAMs were exposed to Cp(allyl)Pd vapor, a Pd (2+)/allyl-terminated SAM surface was obtained (to a lower extent this was also the case for dep. BPDMAc-1 SAMs), which was stable against exposure to H 2 gas. Reduction to Pd (0) by H 2 was only observed when small amounts of Pd (0) were already present, for example, after prolonged exposure to the precursor. The catalytic activity of the small Pd (0) particles also caused a decomposition of the SAMs upon exposure to air.     

Weakly Nonlinear Time-Adiabatic Theory

We revisit the time-adiabatic theorem of quantum mechanics and show that it can be extended to weakly nonlinear situations, that is to nonlinear Schrödinger equations in which either the nonlinear coupling constant or, equivalently, the solution is asymptotically small. To this end, a notion of criticality is introduced at which the linear bound states stay adiabatically stable, but nonlinear effects start to show up at leading order in the form of a slowly varying nonlinear phase modulation. In addition, we prove that in the same regime a class of nonlinear bound states also stays adiabatically stable, at least in terms of spectral projections.     

Protonation‐Driven Membrane Insertion of a pH‐Low Insertion Peptide

The pH‐low insertion peptide (pHLIP) inserts into membranes and forms a transmembrane (TM) α‐helix in response to slight acidity, and has shown great potential for cancer diagnosis and treatment. As a lead, pHLIP is challenging to optimize because the mechanism of its pH‐dependent membrane interactions is not completely understood. Within pHLIP there are multiple D/E residues which could sense the pH change, the particular role played by each of them in the protonation‐driven insertion process is not clear. The precise location of the TM helix within the pHLIP sequence is also unknown. In this work, solid‐state NMR spectroscopy is used to address these central questions. Tracing backbone conformations revealed that the TM helix spans from A10 to D33 with a break at T19 to P20. Residue‐specific pK_a values of D31, D33, D25, and D14 were determined to be 6.5, 6.3, 6.1, and 5.8, respectively, and define the sequence of protonations which lead to insertion. Furthermore, possible intermediate states which disrupt membranes at pH 6.4 were proposed based on tryptophan fluorescence quenching and NMR data.     

Heat‐Flow‐Driven Oligonucleotide Gelation Separates Single‐Base Differences

DNA phase transitions are often induced by the addition of condensation agents or by dry concentration. Herein, we show that the non‐equilibrium setting of a moderate heat flow across a water‐filled chamber separates and gelates DNA strands with single‐base resolution. A dilute mix of DNA with two slightly different gel‐forming sequences separates into sequence‐pure hydrogels under constant physiological solvent conditions. A single base change in a 36 mer DNA inhibits gelation. Only sequences with the ability to form longer strands are concentrated, further elongated, and finally gelated by length‐dependent thermal trapping. No condensation agents, such as multivalent ions, were added. Equilibrium aggregates from dry concentration did not show any sequence separation. RNA is expected to behave identically owing to its equal thermophoretic properties. The highly sequence‐specific phase transition points towards new possibilities for non‐equilibrium origins of life.     

Photodissociation of uracil

We investigate the photochemistry and photodissociation dynamics of uracil by two-colour photofragment Doppler spectroscopy and by two-colour slice imaging at excitation wavelengths between 268 and 235 nm. We observe the loss of a hydrogen atom upon excitation into the pipi* state. The angular distribution indicates a statistical process, while the translational energy distribution agrees with a dissociation that takes place on the electronic ground state. The pipi* state most likely deactivates via the lower-lying npi* state. In addition there is evidence for a second pathway: direct decay of the pipi* state to the electronic ground state with subsequent dissociation. Experiments on uracil-1,3-D(2) show that there is no site selectivity in the dissociation process. No evidence was found for the direct dissociation via a pisigma* excited state that seems to be relevant in the photochemistry of adenine and many other heterocyclic molecules. Overall, the photochemistry of uracil is similar to that of thymine.     

Conformational adaptation and selective adatom capturing of tetrapyridyl-porphyrin molecules on a copper (111) surface

We present a combined low-temperature scanning tunneling microscopy and near-edge X-ray adsorption fine structure study on the interaction of tetrapyridyl-porphyrin (TPyP) molecules with a Cu(111) surface. A novel approach using data from complementary experimental techniques and charge density calculations allows us to determine the adsorption geometry of TPyP on Cu(111). The molecules are centered on "bridge" sites of the substrate lattice and exhibit a strong deformation involving a saddle-shaped macrocycle distortion as well as considerable rotation and tilting of the meso-substituents. We propose a bonding mechanism based on the pyridyl-surface interaction, which mediates the molecular deformation upon adsorption. Accordingly, a functionalization by pyridyl groups opens up pathways to control the anchoring of large organic molecules on metal surfaces and tune their conformational state. Furthermore, we demonstrate that the affinity of the terminal groups for metal centers permits the selective capture of individual iron atoms at low temperature.     

Detection of protein-RNA crosslinks by nanoLC-ESI-MS/MS using precursor ion scanning and multiple reaction monitoring (MRM) experiments

Protein-RNA interactions within ribonucleoprotein particles (RNPs) can be investigated by UV-induced crosslinking of proteins to their cognate RNAs and subsequent isolation and mass-spectrometric analysis of crosslinked peptide-RNA oligonucleotides. Because of the low crosslinking yield, a major challenge in protein-RNA UV crosslinking is the detection of the crosslinked species over the excess of non-crosslinked material, especially when complex systems (native RNPs) are investigated. Here, we applied a novel approach that uses on-line nanoLC-ESI-MS/MS to detect and subsequently sequence peptide-RNA oligonucleotide crosslinks from crude mixtures. To detect the crosslinks we made use of features shared by crosslinks and phosphopeptides, that is, the phosphate groups that both carry. A precursor ion scan for m/z 79 (negative-ion mode, -ve) is applied to selectively detect analytes bearing the phosphate-containing species (i.e., residual non-crosslinked RNA and peptide-RNA crosslinks) from crude mixtures and to determine their exact m/z values. On this basis, a multiple reaction monitoring (MRM) experiment monitors the expected decomposition from the different precursor charge states of the putative crosslinks to one of the four possible RNA nucleobases [m/z 112, 113, 136, 152 (positive-ion mode, +ve)]. On detection, a high-quality MS/MS is triggered to establish the structure of the crosslink. In a feasibility study, we detected and subsequently sequenced peptide-RNA crosslinks obtained by UV-irradiation of (1) native U1 snRNPs and (2) [15.5K-61K-U4atac] snRNPs prepared by reconstitution in vitro. MRM-triggered collision-induced dissociation (CID) MS/MS enabled us to obtain sequence information about the crosslinked peptide and RNA moiety.