Deciphering second harmonic generation signals

Second harmonic generation (SHG) has emerged as one of the most powerful techniques used to selectively monitor surface dynamics and reactions for all types of interfaces as well as for imaging non-centrosymmetric structures, although the molecular origin of the SHG signal is still poorly understood. Here, we present a breakthrough approach to predict and interpret the SHG signal at the atomic level, which is freed from the hyperpolarisability concept and self-consistently considers the non-locality and the coupling with the environment. The direct ab initio method developed here shows that a bulk quadrupole contribution significantly overwhelms the interface dipole term in the purely interfacial induced second-order polarisation for water/air interfaces. The obtained simulated SHG responses are in unprecedented agreement with the experimental signal. This work not only paves the road for the prediction of SHG response from more complex interfaces of all types, but also suggests new insights in the interpretation of the SHG signal at a molecular level. In particular, it highlights the modest influence of the molecular orientation and the high significance of the bulk quadrupole contribution, which does not depend on the interface, in the total experimental response.

Second harmonic generation is one of the most powerful techniques used to selectively probe interfaces of all types. The direct ab initio method developed here allows predicting the signal and highlights the importance of local and non-local effects.     

Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist

Depression is the most common mental illness, affecting approximately 4.4% of the global population. Despite many available treatments, some patients exhibit treatment-resistant depression. Thus, the need to develop new and alternative treatments cannot be overstated. Adenosine receptor antagonists have emerged as a promising new class of antidepressants. The current study investigates a novel dual A₁/A_2A adenosine receptor antagonist, namely 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1H-inden-1-one (1a), for antidepressant capabilities by determining its metabolic profiles and comparing them to those of two reference compounds (imipramine and KW-6002). The metabolic profiles were obtained by treating male Sprague-Dawley rats with 1a and the reference compounds and subjecting them to the forced swim test. Serum and brain material was consequently collected from the animals following euthanasia, after which the metabolites were extracted and analyzed through untargeted metabolomics using both ¹H-NMR and GC-TOFMS. The current study provides insight into compound 1a’s metabolic profile. The metabolic profile of 1a was similar to those of the reference compounds. They potentially exhibit their antidepressive capabilities via downstream effects on amino acid and lipid metabolism.     

Stability of localized structures in degenerate wave mixing

We give experimental proof of the stability of (supercritical) spatial phase solitons in degenerate wave mixing. Received: 16 June 1999 / Published online: 25 August 1999     

Darstellung und Charakterisierung von Thio- und Seleno-closo-hexaboraten sowie Kristallstruktur von (Ph4P)[B6H5Hfac(SH)]

Synthesis and Characterization of the Thio- and Seleno- closo -hexaborates and the Crystal Structure of (Ph₄P)[B₆H₅H^fac(SH)] By treatment of [B₆H₅(SCN)]^2– and [B₆H₅(SeCN)]^2– in strong basic medium the chalcogeno-closo-hexaborates [B₆H₅S]^3– and [B₆H₅Se]^3– are formed. An X-ray structure determination has been performed on the doubly protonated compound (Ph₄P)[B₆H₅H^fac(SH)] (triklin, P 1¯, a = 7.436(2), b = 12.850(2), c = 13.0594(12) Å, α = 93.131(8), β = 94.47(3), γ = 90.40(3)°, Z = 2). The ¹¹B NMR spectra exhibit the characteristic pattern of a monosubtituted B₆ octahedron with the intensity ratio 1 : 4 : 1. The chemical shifts are systematically dependent on the protonation at a facet of the B₆ clusters with H^fac or at the chalcogen atom. Whereas the signals of the equatorial nuclei are nearly at equal positions from –16.0 to –16.9 ppm, the ipso-B atoms absorb in the low field region from –4.7 to –11.7 ppm, and the antipodal-B atoms in the high field from –21.6 to –28.0 ppm. In the IR and Raman spectra the typical B–X and B₆-X stretching vibrations are observed from X = S at 1089 and 383, for X = Se at 1076 and 292 cm^–1, respectively.     

Simulation of High‐Frequency Atmospheric Gas Discharges

The generation of atmospheric gas discharges is an important concern in many industrial applications. We are investigating here a special type of high‐frequency atmospheric gas discharge. The results of modelling the breakdown mechanism and of the development phase of the discharge will be presented. Furthermore we will show first numerical results. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Readily Available Primary Aminoboranes as Powerful Reagents for Aldimine Synthesis

Primary aminoboranes (RNHBR₂), which are readily available by spontaneous dehydrocoupling of amines and boranes cleanly react at room temperature with aldehydes to give aldimines. The overall transformation from amines to aldimines can be conveniently performed by a sequential one‐pot reaction. This synthetic strategy is especially useful for electron poor and bulky amines which are reluctant to react with aldehydes under dehydration conditions. Using a Glorius robustness screen, we show that this methodology is chemoselective, and functional group tolerant. Computational and experimental data support the irreversible formation of the aldimine product in marked contrast with traditional methods.     

Raman Enhancement of Nanoparticle Dimers Self-Assembled Using DNA Origami Nanotriangles

Surface-enhanced Raman scattering is a powerful approach to detect molecules at very low concentrations, even up to the single-molecule level. One important aspect of the materials used in such a technique is how much the signal is intensified, quantified by the enhancement factor (EF). Herein we obtained the EFs for gold nanoparticle dimers of 60 and 80 nm diameter, respectively, self-assembled using DNA origami nanotriangles. Cy5 and TAMRA were used as surface-enhanced Raman scattering (SERS) probes, which enable the observation of individual nanoparticles and dimers. EF distributions are determined at four distinct wavelengths based on the measurements of around 1000 individual dimer structures. The obtained results show that the EFs for the dimeric assemblies follow a log-normal distribution and are in the range of 10⁶ at 633 nm and that the contribution of the molecular resonance effect to the EF is around 2, also showing that the plasmonic resonance is the main source of the observed signal. To support our studies, FDTD simulations of the nanoparticle’s electromagnetic field enhancement has been carried out, as well as calculations of the resonance Raman spectra of the dyes using DFT. We observe a very close agreement between the experimental EF distribution and the simulated values.     

Route scouting and optimization of a potent sulfoximine-based inverse agonist of RORγt

During our research looking for novel inverse agonists of RORγt, we identified a potent sulfoximine-based modulator as one of our pre-clinical candidates for the topical treatment for psoriasis. Herein, we describe the various routes we evaluated during the lead generation and optimization phases and the final route chosen for scale-up to deliver the first 100?g of API.