Regioselective Fluorohydrin Synthesis from Allylsilanes and Evidence for a Silicon-Fluorine Gauche Effect.

Allylsilanes can be regioselectively transformed into the corresponding 3-silylfluorohydrin in good yield using a sequence of epoxidation followed by treatment with HF·Et3N with or without isolation of the intermediate epoxide. Various silicon-substitutions are tolerated, resulting in a range of 2-fluoro-3-silylpropan-1-ol products from this method. Whereas other fluorohydrin syntheses by epoxide opening using HF·Et3N generally require more forcing conditions (e.g., higher reaction temperature), opening of allylsilane-derived epoxides with this reagent occurs at room temperature. We attribute this rate acceleration along with the observed regioselectivity to a ß-silyl effect that stabilizes a proposed cationic intermediate. The use of enantioenriched epoxides indicates that both SN1- and SN2-type mechanisms may be operable depending on substitution at silicon. Conformational analysis by NMR and theory along with a crystal structure obtained by X-ray diffraction points to a preference for silicon and fluorine to be proximal to one another in the products, perhaps favored due to electrostatic interactions.

A MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides.

The marine sponge-derived fungus Stachylidium bicolor 293 K04 is a prolific producer of specialized metabolites, including certain cyclic tetrapeptides called endolides, which are characterized by the presence of the unusual amino acid N-methyl-3-(3-furyl)-alanine. This rare feature can be used as bait to detect new endolide-like analogs through customized fragment pattern searches of tandem mass spectrometry data using the Mass Spec Query Language (MassQL). Here, we integrate endolide-specific MassQL queries with molecular networking to obtain substructural information guiding the targeted isolation and structure elucidation of the new proline-containing endolides E (1) and F (2). We showed that endolide F (but not E) is a moderate antagonist of the arginine vasopressin V1A receptor, a member of the G protein-coupled receptor superfamily.

Quasi-relativistic approach to analytical gradients of parity violating potentials.

An analytic gradient approach for the computation of derivatives of parity-violating (PV) potentials with respect to displacements of the nuclei in chiral molecules is described and implemented within a quasirelativistic mean-field framework. Calculated PV potential gradients are utilized for estimating PV frequency splittings between enantiomers in rotational and vibrational spectra of four chiral polyhalomethanes, i.e., CHBrClF, CHClFI, CHBrFI, and CHAtFI. Values calculated within the single-mode approximation for frequency shifts agree well with previously reported theoretical values. The influence of non-separable anharmonic effects (multi-mode effects) on vibrational frequency shifts, which are readily accessible with the present analytic derivative approach, is estimated for the C-F stretching fundamental of all four molecules and computed for each of the fundamentals in CHBrClF and CHAtFI. Multi-mode effects are found to be significant, in particular, for C-F stretching modes, being for some modes and cases of similar size as the single-mode contribution.

Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions. METHODS: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost. RESULTS: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively (P = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE (P = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [P < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [P = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE. CONCLUSION: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost.

A new route for enantio-sensitive structure determination by photoelectron scattering on molecules in the gas phase.

X-Ray as well as electron diffraction are powerful tools for structure determination of molecules. Studies on randomly oriented molecules in the gas phase address cases in which molecular crystals cannot be generated or the interaction-free molecular structure is to be addressed. Such studies usually yield partial geometrical information, such as interatomic distances. Here, we present a complementary approach, which allows obtaining insight into the structure, handedness, and even detailed geometrical features of molecules in the gas phase. Our approach combines Coulomb explosion imaging, the information that is encoded in the molecular-frame diffraction pattern of core-shell photoelectrons and ab initio computations. Using a loop-like analysis scheme, we are able to deduce specific molecular coordinates with sensitivity even to the handedness of chiral molecules and the positions of individual atoms, e.g., protons.

Relativistic and QED corrections to one-bond indirect nuclear spin-spin couplings in X2 2+ and X3 2+ ions (X = Zn, Cd, Hg).

The indirect spin-spin coupling tensor, J, between mercury nuclei in systems containing this element can be of the order of a few kHz and one of the largest measured. We analyzed the physics behind the electronic mechanisms that contribute to the one- and two-bond couplings nJHg-Hg (n = 1, 2). For doing so, we performed calculations for J-couplings in the ionized X2 2+ and X3 2+ linear molecules (X = Zn, Cd, Hg) within polarization propagator theory using the random phase approximation and the pure zeroth-order approximation with Dirac-Hartree-Fock and Dirac-Kohn-Sham orbitals, both at four-component and zeroth-order regular approximation levels. We show that the "paramagnetic-like" mechanism contributes more than 99.98% to the total isotropic value of the coupling tensor. By analyzing the molecular and atomic orbitals involved in the total value of the response function, we find that the s-type valence atomic orbitals have a predominant role in the description of the coupling. This fact allows us to develop an effective model from which quantum electrodynamics (QED) effects on J-couplings in the aforementioned ions can be estimated. Those effects were found to be within the interval (0.7; 1.7)% of the total relativistic effect on isotropic one-bond 1J coupling, though ranging those corrections between the interval (-0.4; -0.2)% in Zn-containing ions, to (-1.2; -0.8)% in Hg-containing ions, of the total isotropic coupling constant in the studied systems. The estimated QED corrections show a visible dependence on the nuclear charge Z of each atom X in the form of a power-law proportional to ZX 5.

Accurate ab initio calculations of RaF electronic structure appeal to more laser-spectroscopical measurements.

Recently, a breakthrough has been achieved in laser-spectroscopic studies of short-lived radioactive compounds with the first measurements of the radium monofluoride molecule (RaF) UV/vis spectra. We report results from high-accuracy ab initio calculations of the RaF electronic structure for ground and low-lying excited electronic states. Two different methods agree excellently with experimental excitation energies from the electronic ground state to the 2Π1/2 and 2Π3/2 states, but lead consistently and unambiguously to deviations from experimental-based adiabatic transition energy estimates for the 2Σ1/2 excited electronic state, and show that more measurements are needed to clarify spectroscopic assignment of the 2Δ state.

Instanton calculations of tunneling splittings in chiral molecules.

We report the ground state tunneling splittings (ΔE± ) of a number of axially chiral molecules using the ring-polymer instanton (RPI) method (J. Chem. Phys., 2011, 134, 054109). The list includes isotopomers of hydrogen dichalcogenides H2 X2 (X = O, S, Se, Te, and Po), hydrogen thioperoxide HSOH and dichlorodisulfane S2 Cl2 . Ab initio electronic-structure calculations have been performed on the level of second-order Møller-Plesset perturbation (MP2) theory either with split-valance basis sets or augmented correlation-consistent basis sets on H, O, S, and Cl atoms. Energy-consistent pseudopotential and corresponding triple zeta basis sets of the Stuttgart group are used on Se, Te, and Po atoms. The results are further improved using single point calculations performed at the coupled cluster level with iterative singles and doubles and perturbative triples amplitudes. When available for comparison, our computed values of ΔE± are found to lie within the same order of magnitude as values reported in the literature, although RPI also provides predictions for H2 Po2 and S2 Cl2 , which have not previously been directly calculated. Since RPI is a single-shot method which does not require detailed prior knowledge of the optimal tunneling path, it offers an effective way for estimating the tunneling dynamics of more complex chiral molecules, and especially those with small tunneling splittings.

High-Spin Imido Cobalt Complexes with Imidyl Radical Character*.

We report on the synthesis of a variety of trigonal imido cobalt complexes [Co(NAryl)L2 ]- , (L=N(Dipp)SiMe3 ), Dipp=2,6-diisopropylphenyl) with very long Co-NAryl bonds of around 1.75 Å. Their electronic structure was interrogated using a variety of physical and spectroscopic methods such as EPR or X-Ray absorption spectroscopy which leads to their description as highly unusual imidyl cobalt complexes. Computational analyses corroborate these findings and further reveal that the high-spin state is responsible for the imidyl character. Exchange of the Dipp substituent on the imide by the smaller mesityl function (2,4,6-trimethylphenyl) effectuates the unexpected Me3 Si shift from the ancillary ligand set to the imidyl nitrogen, revealing a highly reactive, nucleophilic character of the imidyl unit.

Chiral Molecules as Sensitive Probes for Direct Detection of P-Odd Cosmic Fields.

Potential advantages of chiral molecules for a sensitive search for parity violating cosmic fields are highlighted. Such fields are invoked in different models for cold dark matter or in the Lorentz-invariance violating standard model extensions and thus are signatures of physics beyond the standard model. The sensitivity of a 20-year-old experiment with the molecule CHBrClF to pseudovector cosmic fields as characterized by the parameter |b_{0}^{e}| is estimated to be O(10^{-12} GeV) employing ab initio calculations. This allows us to project the sensitivity of future experiments with favorable choices of chiral heavy-elemental molecular probes to be O(10^{-17} GeV), which will be an improvement of the present best limits by at least two orders of magnitude.

High-resolution resonance-enhanced multiphoton photoelectron circular dichroism.

Photoelectron circular dichroism (PECD) is a highly sensitive enantiospecific spectroscopy for studying chiral molecules in the gas phase using either single-photon ionization or multiphoton ionization. In the short pulse limit investigated with femtosecond lasers, resonance-enhanced multiphoton ionization (REMPI) is rather instantaneous and typically occurs simultaneously via more than one vibrational or electronic intermediate state due to limited frequency resolution. In contrast, vibrational resolution in the REMPI spectrum can be achieved using nanosecond lasers. In this work, we follow the high-resolution approach using a tunable narrow-band nanosecond laser to measure REMPI-PECD through distinct vibrational levels in the intermediate 3s and 3p Rydberg states of fenchone. We observe the PECD to be essentially independent of the vibrational level. This behaviour of the chiral sensitivity may pave the way for enantiomer specific molecular identification in multi-component mixtures: one can specifically excite a sharp, vibrationally resolved transition of a distinct molecule to distinguish different chiral species in mixtures.

Variation of the Fine-Structure Constant in Model Systems for Singlet Fission.

Energetic conditions that are required for favorable singlet exciton fission, an intermolecular electron correlation effect, are studied with relativistic quantum chemical methods as to investigate the effect of a varying fine-structure constant. Ethylene and derivatives thereof serve as simple model systems, whereas pentacene and perfluoropentacene, which display singlet exciton fission experimentally, are used as specific examples for possible applications. Effects are estimated to be small in this class of compounds, but substitution with heavier halogens might lead to oppositely shifting energy levels and thereby improved sensitivity in narrow resonance situations.

Toolbox approach for quasi-relativistic calculation of molecular properties for precision tests of fundamental physics.

A generally applicable approach for the calculation of relativistic properties described by one-electron operators within a two-component wave function approach is presented. The formalism is explicitly evaluated for the example of quasirelativistic wave functions obtained within the zeroth order regular approximation (ZORA). The wide applicability of the scheme is demonstrated for the calculation of parity (P) and time-reversal (T ) symmetry violating properties, which are important for searches of physics beyond the standard model of particle physics. The quality of the ZORA results is shown exemplarily for the molecules RaF and TlF by comparison with data from four-component calculations as far as available. Finally, the applicability of RaF in experiments that search for P,T-violation not only in the electronic but also in the quark sector is demonstrated.

Synthesis and Characterization of [Br3 ][MF6 ] (M=Sb, Ir), as well as Quantum Chemical Study of [Br3 ]+ Structure, Chemical Bonding, and Relativistic Effects Compared with [XBr2 ]+ (X=Br, I, At, Ts) and [TsZ2 ]+ (Z=F, Cl, Br, I, At, Ts).

[Br3 ][SbF6 ] and [Br3 ][IrF6 ] were synthesized by interaction of BrF3 with Sb2 O3 or iridium metal, respectively. The former compound crystallizes in the orthorhombic space group Pbcn (No. 60) with a=11.9269(7), b=11.5370(7), c=12.0640(6) Å, V=1660.01(16) Å3 , Z=8 at 100 K. The latter compound crystallizes in the triclinic space group P 1 ‾ (No. 2) with a=5.4686(5), b=7.6861(8), c=9.9830(9) Å, α=85.320(8), ß=82.060(7), γ=78.466(7)°, V=406.56(7) Å3 , Z=2 at 100 K. Both compounds contain the cation [Br3 ]+ , which has a bent structure and is coordinated by octahedron-like anions [MF6 ]- (M=Sb, Ir). Experimentally obtained cell parameters, bond lengths, and angles are confirmed by solid-state DFT calculations, which differ from the experimental values by less than 2 %. Relativistic effects on the structure of the tribromonium(1+) cation are studied computationally and found to be small. For the heaviest analogues containing At and Ts, however, pronounced relativistic effects are found, which lead to a linear structure of the polyhalogen cation.

Design Principles for the Atomic and Electronic Structure of Halide Perovskite Photovoltaic Materials: Insights from Computation.

In the current decade, perovskite solar cell research has emerged as a remarkably active, promising, and rapidly developing field. Alongside breakthroughs in synthesis and device engineering, halide perovskite photovoltaic materials have been the subject of predictive and explanatory computational work. In this Minireview, we focus on a subset of this computation: density functional theory (DFT)-based work highlighting the ways in which the electronic structure and band gap of this class of materials can be tuned via changes in atomic structure. We distill this body of computational literature into a set of underlying design principles for the band gap engineering of these materials, and rationalize these principles from the viewpoint of band-edge orbital character. We hope that this perspective provides guidance and insight toward the rational design and continued improvement of perovskite photovoltaics.

Towards Ultracold Chiral Molecules.

Atoms can be cooled and trapped efficiently with the help of lasers. So-called Doppler cooling takes advantage of momentum transfer upon absorption and emission of photons and of Doppler shifts to facilitate effectively closed optical absorption-emission loops, by which atoms are slowed down and cooled. Due to the wealth of internal degrees of freedom accessible in molecules, it was assumed for a long time that similarly closed optical loops cannot be realised for molecules. After an early theoretical proposal by Di Rosa for diatomic molecules, such cooling has been achieved in this decade for SrF, YO, CaF and YbF. It has been outlined recently that also polyatomic molecules should be coolable with lasers and classes of molecules expected to be amenable to this have been proposed by the present authors. Experimental success in laser cooling of SrOH has been reported. The status of cooling polyatomic molecules with lasers and the prospects for obtaining ultracold chiral molecules is reviewed herein.

Investigating Absolute Stereochemical Configuration with Coulomb Explosion Imaging.

It is a particularly challenging task in stereochemistry to determine the absolute configuration of chiral molecules, i.e. to assign to a given sample the microscopic enantiomeric structure. In recent years, Coulomb Explosion Imaging (CEI) has been shown to yield directly the absolute configuration of small molecules in the gas phase. This contribution describes the experimental basics of this approach, highlights the most significant results and discusses limitations. A short discussion on extending Coulomb Explosion Imaging beyond analytic aspects to fundamental questions of molecular chirality concludes this review.

Barium as Honorary Transition Metal in Action: Experimental and Theoretical Study of Ba(CO)+ and Ba(CO).

Ba(CO)+ and Ba(CO)- have been produced and isolated in a low-temperature neon matrix. The observed C-O stretching wavenumber for Ba(CO)+ of 1911.2 cm-1 is the most red-shifted value measured for any metal carbonyl cations, indicating strong π backdonation of electron density from Ba+ to CO. Quantum chemical calculations indicate that Ba(CO)+ has a 2 Π reference state, which correlates with the 2 D(5d1 ) excited state of Ba+ that comprises significant Ba+ (5dπ1 )→CO(π* LUMO) backbonding, letting the Ba(CO)+ complex behave like a conventional transition-metal carbonyl. A bonding analysis shows that the π backdonation in Ba(CO)+ is much stronger than the Ba+ (5dσ /6s)←CO(HOMO) σ donation. The Ba+ cation in the 2 D(5d1 ) excited state is a donor rather than an acceptor. Covalent bonding in the radical anion Ba(CO)- takes place mainly through Ba(5dπ )←CO- (π* SOMO) π donation and Ba(5dσ /6s)←CO- (HOMO) σ donation. The most important valence functions at barium in Ba(CO)+ cation and Ba(CO)- anion are the 5d orbitals.

Heptacene: Characterization in Solution, in the Solid State, and in Films.

Acenes comprise an important class of organic semiconducting materials. As graphene nanoribbons of ultimate width, they are valuable atom-precise model systems for studying the properties of this form of nanoscale carbon materials. Heptacene is the smallest member of the acene series that could only be studied under matrix isolation conditions. Its existence in bulk had never been positively confirmed, despite efforts dating back more than 70 years. We report that the reduction of 7,16-heptacenequinone produces a mixture of two diheptacene molecules. The diheptacenes undergo thermal cleavage to heptacene at high temperatures in the solid state. Monitoring this cycloreversion by solid state 13C cross-polarized magic angle spinning NMR reveals that solid heptacene has a half-life time of several weeks at room temperature. The diheptacenes are valuable precursors for generating films of heptacene by vapor phase deposition that can be studied below or at room temperature.