Anti-SARS-CoV-2 Activity and Cytotoxicity of Amaryllidaceae Alkaloids from .

The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from led to the identification of three previously undescribed compounds: -demethyl-norlycoramine (), (-)-2--pseudolycorine () and (+)-2--pseudolycorine (), together with eight known compounds: 6α-hydroxyhippeastidine (), 6β-hydroxyhippeastidine (), lycorine (), 2--lycorine (), zephyranthine (), ungeremine (), pancratistatin () and 9--demethyl-7--methyllycorenine ().

Epimeric Mixture Analysis and Absolute Configuration Determination Using an Integrated Spectroscopic and Computational Approach-A Case Study of Two Epimers of 6-Hydroxyhippeastidine.

Structural elucidation has always been challenging, and misassignment remains a stringent issue in the field of natural products. The growing interest in discovering unknown, complex natural structures accompanies the increasing awareness concerning misassignments in the community. The combination of various spectroscopic methods with molecular modeling has gained popularity in recent years.

Vibrational Optical Activity Study of Four Antibiotic (Lipo)glycopeptides: Vancomycin, Oritavancin, Dalbavancin, and Teicoplanin.

The antibiotic glycopeptide class, of which vancomycin is the original compound, has received due attention over the past few decades in search of antibiotics to overcome resistances developed by bacteria. Crucial for the understanding and further development of glycopeptides that possess desired antibacterial effects is the determination of their conformational behavior, as this sheds light on the mechanism of action of the compound. Among others, vibrational optical activity (VOA) techniques (vibrational circular dichroism and Raman optical activity) can be deployed for this, but the question remains to what extent these spectroscopic techniques can provide information concerning the molecular class under investigation.

Comparative Study of the Vibrational Optical Activity Techniques in Structure Elucidation: The Case of Galantamine.

The absolute configuration of the alkaloid galantamine was studied using a range of solution-state techniques; nuclear magnetic resonance (NMR), vibrational circular dichroism (VCD), and Raman optical activity (ROA). While the combined use of NMR and VCD does provide a fast, high-resolution methodology for determining the absolute configuration of galantamine, both techniques were needed in concert to achieve this goal. ROA, on the other hand, proved to be sensitive enough to assign the full absolute configuration without relying on other techniques.

Carbamate Synthesis Using a Shelf-Stable and Renewable C Reactant.

4-Propylcatechol carbonate is a shelf-stable, renewable C reactant. It is easily prepared from renewable 4-propylcatechol (derived from wood) and dimethyl carbonate (derived from CO ) using a reactive distillation system. In this work, the 4-propylcatechol carbonate is used for the two-step synthesis of carbamates under mild reaction conditions.

Vibrational Circular Dichroism Sheds New Light on the Competitive Effects of Crowding and β-Synuclein on the Fibrillation Process of α-Synuclein.

The effects of crowding, using the crowding agent Ficoll 70, and the presence of β-synuclein on the fibrillation process of α-synuclein were studied by spectroscopic techniques, transmission electron microscopy, and thioflavin T assays. This combined approach, in which all techniques were applied to the same original sample, generated an unprecedented understanding of the effects of these modifying agents on the morphological properties of the fibrils. Separately, crowding gives rise to shorter mutually aligned fibrils, while β-synuclein leads to branched, short fibrils.

Exploiting the σ-Hole Concept: An Infrared and Raman-Based Characterization of the S⋅⋅⋅O Chalcogen Bond between 2,2,4,4-Tetrafluoro-1,3-dithiethane and Dimethyl Ether.

In the last decade, halogen bonds, noncovalent interactions formed between positive regions in the electrostatic potential on halogen atoms, often referred to as σ-holes, and electron-rich sites, have gained a lot of interest. Recently, this interest has been expanded towards interactions with Group V and Group VI elements, giving rise to pnicogen and chalcogen bonds. Although chalcogen bonds have already shown some promising results for applications in crystallography and catalysis, experimental results characterising these noncovalent interactions remain scarce.

Effect of Fluorination on the Competition of Halogen Bonding and Hydrogen Bonding: Complexes of Fluoroiodomethane with Dimethyl Ether and Trimethylamine.

To further rationalize the competition between halogen and hydrogen bonding, a combined experimental and theoretical study on the weakly bound molecular complexes formed between the combined halogen bond/hydrogen bond donor fluoroiodomethane and the Lewis bases dimethyl ether and trimethylamine (in standard and fully deuterated form) is presented. The experimental data are obtained by recording infrared and Raman spectra of mixtures of the compounds in liquid krypton, at temperatures between 120 and 156 K. The experiments are supported by ab initio calculations at the MP2/aug-cc-pVDZ-PP level, statistical thermodynamics and Monte Carlo free energy perturbation calculations.

Taking the halogen bonding-hydrogen bonding competition one step further: complexes of difluoroiodomethane with trimethylphosphine, dimethyl sulfide and chloromethane.

To rationalize the driving factors in the competition of halogen bonding and hydrogen bonding, the complexes of the combined halogen-/hydrogen-bond donor difluoroiodomethane with the Lewis bases trimethylphosphine, dimethyl sulfide and chloromethane are studied. For all Lewis bases, ab initio calculations lead to halogen- and hydrogen-bonded complexes. Fourier transform-IR experiments involving solutions of mixtures of difluoroiodomethane with trimethylphosphine(-d) or dimethyl sulfide(-d) in liquid krypton confirm the coexistence of a halogen-bonded and hydrogen-bonded complex.

Dimers or trimers? A characterization of the halogen bonded complexes of CFX (X=I or Br) with dimethyl ether and acetone in cryosolutions.

Acetone molecules dissolved in liquid krypton are inclined to self-associate into dimers. This behavior affects its use as a prototype Lewis base in studies of weak intermolecular interactions. In this study infrared spectra of mixed solutions of dimethyl ether and CFX and of acetone and CFX (with X=I or Br) dissolved in liquid argon and liquid krypton are recorded at constant temperature.

Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers.

Electrospray ion mobility-mass spectrometry (IM-MS) data show that for some small molecules, two (or even more) ions with identical sum formula and mass, but distinct drift times are observed. In spite of showing their own unique and characteristic fragmentation spectra in MS/MS, no configurational or constitutional isomers are found to be present in solution. Instead the observation and separation of such ions appears to be inherent to their gas-phase behaviour during ion mobility experiments.

Rotational Study of Dimethyl Ether-Chlorotrifluoroethylene: Lone Pair···π Interaction Links the Two Subunits.

The rotational spectra of two isotopologues of chlorotrifluoroethylene-dimethyl ether show that the two constituent molecules are held together by a lone pair···π interaction. The ether oxygen is linked to the (CF2) carbon atom, with a C-O distance of 2.908 Å.

Self-Associating Behavior of Acetone in Liquid Krypton.

Acetone molecules are inclined to self-associate through dipole-dipole interactions because of their large dipole moment. Infrared spectroscopy of compounds dissolved in liquid noble gases supported by high level ab initio calculations allows investigating the self-associating behavior and determining the thermodynamical properties. In this study, infrared spectra of various concentrations of acetone dissolved in liquid krypton are recorded at constant temperature.

Mechanism of the Cu-catalyzed benzylic oxygenation of (aryl)(heteroaryl)methanes with oxygen.

A mechanistic study of the copper-catalyzed oxidation of the methylene group of aryl(di)azinylmethanes was performed. Initial reaction rates were measured making use of IR reaction monitoring and a kinetic analysis of the reaction was executed. The reaction proved to be first order in oxygen concentration.

Exploring the limits of cryospectroscopy: Least-squares based approaches for analyzing the self-association of HCl.

To rationalize the concentration dependent behavior observed for a large spectral data set of HCl recorded in liquid argon, least-squares based numerical methods are developed and validated. In these methods, for each wavenumber a polynomial is used to mimic the relation between monomer concentrations and measured absorbances. Least-squares fitting of higher degree polynomials tends to overfit and thus leads to compensation effects where a contribution due to one species is compensated for by a negative contribution of another.

Microwave, r0 Structural Parameters, Conformational Stability, and Vibrational Assignment of (Chloromethyl)fluorosilane.

The FT-microwave spectrum (6.5-26 GHz) of (chloromethyl)fluorosilane (ClCH2-SiH2F) has been recorded and 250 transitions for the parent species along with (13)C, (37)Cl, (29)Si, and (30)Si isotopologues have been assigned for trans conformer. Infrared spectra (3100 to 400 cm(-1)) of gas, solid, and the variable temperature (-100 to -60 °C) studies of the infrared spectra of the sample dissolved in xenon have been recorded.

Expanding Lone Pair···π Interactions to Nonaromatic Systems and Nitrogen Bases: Complexes of C2F3X (X = F, Cl, Br, I) and TMA-d9.

The molecular electrostatic potential surface of unsaturated, locally electron-deficient molecules shows a positive region perpendicular to (a part of) the molecular framework. In recent years it has been shown both theoretically and experimentally that molecules are able to form noncovalent interactions with Lewis bases through this π-hole. When studying unsaturated perfluorohalogenated molecules containing a higher halogen atom, a second electropositive region is also observed near the halogen atom.

Chiroptical studies on brevianamide B: vibrational and electronic circular dichroism confronted.

Chiroptical spectroscopies, such as electronic circular dichroism (ECD) and vibrational circular dichroism (VCD), are highly sensitive techniques to probe molecular conformation, configuration, solvation, and aggregation. Here we report the application of these techniques to study the fungal metabolite brevianamide B. Comparison of the experimental ECD and VCD spectra with the density functional theory simulated counterparts establishes that VCD is the more reliable technique to assign absolute configuration due to the larger functional and dispersion dependence of computed ECD spectra.

N lone-pair···π interaction: a rotational study of chlorotrifluoroethylene···ammonia.

The rotational spectra of four isotopologues of the adduct C2F3Cl-NH3 show that NH3 is bound to the partner molecule through a (N)lone-pair···π interaction. Ammonia is located in proximity to the C2 atom (the one linked to two fluorine atoms), with the C2···N distance = 2.987(2) Å.

Competition of C(sp²)-X···O halogen bonding and lone pair···π interactions: cryospectroscopic study of the complexes of C₂F₃X (X = F, Cl, Br, and I) and dimethyl ether.

Inspection of the electrostatic potential of C2F3X (X = F, Cl, Br, and I) revealed a second electropositive region in the immediate vicinity of the C═C double bond apart from the σ hole of chlorine, bromine, and iodine, leading to C(sp(2))-X···Y halogen bonding, through which complexes stabilized by so-called lone pair···π interactions can be formed. Consequently, the experimental studies for the complexes of dimethyl ether with C2F3X (X = F, Cl, Br, and I) not only allowed one to experimentally characterize and rationalize the effects of hybridization on halogen bonding but, for the first time, also allowed the competition of C-X···Y halogen bonding and lone pair···π interactions to be studied at thermodynamic equilibrium. Analysis of the infrared and Raman spectra reveals that in the cryosolutions of dimethyl ether and C2F3I, solely the halogen-bonded complex is present, whereas C2F3Br and C2F3Cl give rise to a lone pair···π bonded complex as well as a halogen-bonded complex.

A cryospectroscopic infrared and Raman study of the CX⋯π halogen bonding motif: complexes of the CF3Cl, CF3Br, and CF3I with ethyne, propyne and 2-butyne.

Experimental information on the C-X⋯π halogen bonding motif was obtained by studying the formation of molecular complexes of CF3Cl, CF3Br and CF3I with ethyne, propyne and 2-butyne in liquid krypton, using FTIR and Raman spectroscopy. For CF3Br, experimental evidence was found for the formation of 1:1 complexes with propyne and 2-butyne only, while for CF3I spectroscopic features confirming the existence of the halogen bonded complexes were observed for ethyne, propyne and 2-butyne. In addition, at higher concentrations of CF3I and 2-butyne, weak absorptions due to a 2:1 complex were also observed.

Tuning the halogen/hydrogen bond competition: a spectroscopic and conceptual DFT study of some model complexes involving CHF2I.

Insight into the key factors driving the competition of halogen and hydrogen bonds is obtained by studying the affinity of the Lewis bases trimethylamine (TMA), dimethyl ether (DME), and methyl fluoride (MF) towards difluoroiodomethane (CHF(2) I). Analysis of the infrared and Raman spectra of solutions in liquid krypton containing mixtures of TMA and CHF(2) I and of DME and CHF(2) I reveals that for these Lewis bases hydrogen and halogen-bonded complexes appear simultaneously. In contrast, only a hydrogen-bonded complex is formed for the mixtures of CHF(2) I and MF.

Statistical Validation of Absolute Configuration Assignment in Vibrational Optical Activity.

Chiroptical spectroscopy usually requires theoretically computed spectra to assist in the elucidation of the absolute configuration of samples for which experimental spectra have been recorded. Due to the inherently different nature of these two types of spectra, perfect agreement is quasi impossible. Several methods exist to quantify the degree of similarity between the two spectra, but rather limited work has been done to evaluate the robustness of the similarity between theory and experiment.

Experimental characterization of C-X···Y-C (X = Br, I; Y = F, Cl) halogen-halogen bonds.

Using FTIR and Raman spectroscopy, we investigated the formation of halogen bonded complexes of the trifluorohalomethanes CF3Cl, CF3Br, and CF3I with the halomethanes CH3F and CH3Cl and the haloethanes C2H5F and C2H5Cl dissolved in liquid krypton. For CF3Br and CF3I, evidence was found for the formation of C-X···F and C-X···Cl halogen bonded 1:1 complexes. Using spectra recorded at different temperatures, we determined the complexation enthalpies for the complexes to be -7.

Mechanistic and chiroptical studies on the desulfurization of epidithiodioxopiperazines reveal universal retention of configuration at the bridgehead carbon atoms.

The stereochemistry of the desulfurization products of chiral natural and synthetic 3,6-epidithiodiketopiperazines (ETPs) is specified inconsistently in the literature. Qualitative mechanisms have been put forward to explain apparently divergent stereochemical pathways, but the quantitative feasibility of such mechanistic pathways has not been assessed. We report a computational study revealing that desulfurization of ETPs should occur universally with retention of configuration.