Publications by authors named "Wouter Herrebout"

85 Publications

Antiplasmodial Oleanane Triterpenoids from Root Bark.

J Nat Prod 2021 Mar 5;84(3):666-675. Epub 2021 Mar 5.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

Phytochemical investigation of the -BuOH extract of the roots of Sc. Elliot (Combretaceae) led to the isolation and identification of 10 oleanane triterpenoids (-), among which six new compounds, i.e., albidanoside A (), albidic acid A (), albidinolic acid (), albidienic acid (), albidolic acid (), and albidiolic acid (), and two triterpenoid aglycones, i.e., albidic acid B () and albidic acid C (), were isolated here for the first time from a natural source, along with two known compounds. The structures of these constituents were established by means of 1D and 2D NMR spectroscopy and ESI mass spectrometry. The isolated compounds were evaluated for their antiplasmodial and antimicrobial activity against the chloroquine-resistant strain K1, , and . Compounds -, , , and showed moderate antiplasmodial activity with IC values between 5 and 15 μM. None of the tested compounds were active against or . These findings emphasize the potential of as a source for discovery of new antiplasmodial compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.0c01119DOI Listing
March 2021

Synthesis, Structure and Photophysical Properties of a New Class of Inherently Chiral Boron(III) Chelates-The tert-Leucine Complexes.

Chemistry 2021 Mar 16;27(16):5246-5258. Epub 2021 Feb 16.

Molecular Photonics Laboratory, School of Natural and Environmental Sciences, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

A new family of boron(III) chelates is introduced whereby molecular chirality, confirmed by circular dichroism, is imported during synthesis such that isolation of the diastereoisomers does not require separation procedures. The photophysical properties of two members of the family have been examined: the N,O,O-salicylaldehyde-based derivative shows pronounced intramolecular charge-transfer character in fluid solution and is weakly fluorescent, with a large Stokes shift. The corresponding 2-methylamino-benzaldehyde-derived N,N,O-chelate absorbs and fluoresces in the visible region with a much smaller Stokes shift. Orange fluorescence is also observed for this compound as a cast film. Temperature-dependence studies show that decay of the fluorescent state is weakly activated but emission is less than quantitative at 77 K. Quite rare for boron(III)-based chelates, this derivative undergoes intersystem crossing to form a meta-stable triplet-excited state. X-ray crystal structures are reported for both compounds, along with simulated ECD spectra.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202005246DOI Listing
March 2021

CFA-18: a homochiral metal-organic framework (MOF) constructed from rigid enantiopure bistriazolate linker molecules.

Dalton Trans 2020 Nov;49(44):15758-15768

Institute of Physics, Chair of Solid State and Materials Science Augsburg University, Universitätsstrasse 1, 86159 Augsburg, Germany.

In this work, we introduce the first enantiopure bistriazolate-based metal-organic framework, CFA-18 (Coordination Framework Augsburg-18), built from the R-enantiomer of 7,7,7',7'-tetramethyl-6,6',7,7'-tetrahydro-3H,3'H-5,5'-spirobi[indeno[5,6-d]-[1,2,3]triazole] (H2-spirta). The enantiopurity and absolute configuration of the new linker were confirmed by several chiroselective methods. Reacting H2-spirta in hot N,N-dimethylformamide (DMF) with manganese(ii) chloride gave CFA-18 as colorless crystals. The crystal structure with the composition [Mn2Cl2(spirta)(DMF)2] was solved using synchrotron single-crystal X-ray diffraction. CFA-18 shows a framework topology that is closely related to previously reported metal-azolate framework (MAF) structures in which the octahedrally coordinated manganese(ii) ions are triazolate moieties, and the chloride anions form crosslinked one-dimensional helical chains, giving rise to hexagonal channels. In contrast to MAFs crystallizing in the centrosymmetric space group R3[combining macron], the handedness of the helices found in CFA-18 is strictly uniform, leading to a homochiral framework that crystallizes in the trigonal crystal system within the chiral space group P3121 (no. 152).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0dt02847aDOI Listing
November 2020

A combined Raman optical activity and vibrational circular dichroism study on artemisinin-type products.

Phys Chem Chem Phys 2020 Aug;22(32):18014-18024

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.

Artemisinin and two of its derivatives, dihydroartemisinin and artesunate, which are front line drugs against malaria, were investigated using Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments, both supported by density functional theory (DFT) level calculations. The experimental techniques combined with DFT calculations could show that dihydroartemisinin was present as an epimeric mixture in solution. In addition, an approximation of the epimeric ratio could be extracted which was in agreement with the ratio obtained by 1H-NMR spectroscopy. The current study also demonstrates that both ROA and VCD are able to assign the correct absolute configuration (AC) of artemisinin and artesunate out of all their possible diastereomers without any explicit knowledge on their correct stereochemistry and accentuates the synergetic effect between ROA and VCD in AC determination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp03257cDOI Listing
August 2020

Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling.

Chembiochem 2020 Oct 2;21(20):2982-2990. Epub 2020 Jul 2.

University of Namur (UNamur), NARILIS, Department of Chemistry, rue de Bruxelles 61, 5000, Namur, Belgium.

d-Glycero-d-manno-heptose-1β,7-bisphosphate (HBP) and d-glycero-d-manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbic.202000319DOI Listing
October 2020

Chiral Phase Transfer Catalysis in the Asymmetric Synthesis of a 3,3-Disubstituted Isoindolinone and Determination of Its Absolute Configuration by VCD Spectroscopy.

Molecules 2020 May 12;25(10). Epub 2020 May 12.

Dipartimento di Chimica e Biologia, Università di Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy.

In this work we report our endeavors toward the development of an asymmetric synthesis of a 3,3-disubstituted isoindolinone, dimethyl 2-(1-methyl-3-oxoisoindolin-1-yl)malonate, via asymmetric cascade reaction of 2-acetylbenzonitrile with dimethylmalonate and the determination of its absolute configuration (AC) by vibrational circular dichroism (VCD). Bifunctional ammonium salts, derived from 1,2-cyclohexanediamine in combination with inorganic bases under phase transfer conditions, were the most effective catalytic systems, leading to the target in high yields and moderate enantioselectivity. An efficient process of heterochiral crystallization allowed the increase of the enantiopurity up to 96% ee and in an acceptable overall yield. An important aim of the present work is the comparison of different VCD methodologies for AC determination of the target compound.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25102272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287911PMC
May 2020

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

ACS Omega 2019 Aug 19;4(9):14133-14139. Epub 2019 Aug 19.

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.

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. In both cases, statistical validation was applied to aid the determination of absolute configuration. In the case of galantamine, ROA combined with statistical validation is shown to be a powerful stand-alone tool for absolute configuration determination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b02108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714543PMC
August 2019

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

ChemSusChem 2019 Jul 11;12(13):3103-3114. Epub 2019 Jun 11.

Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

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. In the first step, 4-propylcatechol carbonate is treated with an alcohol at 50-80 °C in the presence of a Lewis acid catalyst, such as Zn(OAc) ⋅2 H O. With liquid alcohols, no solvent is used and with solid alcohols 2-methyltetrahydrofuran is used as solvent. In the second step, the alkyl 2-hydroxy-propylphenyl carbonate intermediates obtained react with amines at room temperature in 2-methyltetrahydrofuran, forming the target carbamates and the byproduct 4-propylcatechol, which can be recycled into a carbonate reactant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cssc.201900406DOI Listing
July 2019

Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity.

Chirality 2019 01 23;31(1):21-33. Epub 2018 Nov 23.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.

A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high-pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO-A selectively and competitively. In particular, the R enantiomer was detected as an exceptionally potent and a selective MAO-A inhibitor (K  = 0.85 × 10  ± 0.05 × 10  μM and SI: 2.35 × 10 ), whereas S was determined as poorer compound than R in terms of K and SI (0.184 ± 0.007 and 0.001). The selectivity of the enantiomers was explained by molecular modeling docking studies based on the PDB enzymatic models of MAO isoforms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chir.23027DOI Listing
January 2019

Tracking Conformational Changes in Phosvitin throughout a Crowding-Agent-Based Titration.

Chembiochem 2019 03 29;20(6):770-777. Epub 2019 Jan 29.

Molecular Spectroscopy Group, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

The sensitivity of Raman optical activity (ROA) towards small conformational changes is explored by tracking the structural changes in an intrinsically disordered protein-phosvitin-induced by different concentrations of crowding agent. It is shown that ROA is capable of tracking small conformational changes involving β-sheet and α-helical secondary structural properties of the protein. Furthermore, it is indicated that the influences of the crowding agents employed, Ficoll 70 and dextran 70, on the structural properties of phosvitin differ significantly, with the structural changes induced by the presence of Ficoll 70 being more pronounced and already being visible at a lower concentration. The data also suggest that some spectral changes do not arise from a change in the secondary structure of the protein, but are related to differences in interaction between the phosphorylated residues of the protein and the sugar-based crowding agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbic.201800581DOI Listing
March 2019

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

Biochemistry 2018 10 3;57(41):5989-5995. Epub 2018 Oct 3.

Molecular Spectroscopy Group, Department of Chemistry , University of Antwerp , 2020 Antwerp , Belgium.

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. The combination of both effects leads to short, branched, mutually aligned fibrils. Moreover, it is shown that the nondestructive technique of vibrational circular dichroism is extremely sensitive to the length and the higher-order morphology of the fibrils.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.biochem.8b00780DOI Listing
October 2018

Model-averaging of ab initio spectra for the absolute configuration assignment via vibrational circular dichroism.

Phys Chem Chem Phys 2017 Oct;19(41):28028-28036

Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via G. Paolo II, 132, Fisciano 84084, Italy.

Vibrational absorption and vibrational circular dichroism spectra (VA and VCD) have been recorded for two hybrid isoindolinone-phtalide stereoisomers dissolved in CDCl. Density-functional calculations have been performed to determine their absolute configuration. A comparison of calculated and measured values has been made using several goodness-of-fit indicators, and also introducing a model-averaging technique, taking into account the variation of calculated spectra with the details of the computational method. The model-averaging technique, preliminarily tested on two VCD spectra already assigned to two diastereomers of tadalafil, gives higher credibility to the ab initio calculations, and should be useful for other molecules with high flexibility and/or more than one stereogenic center.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7cp05358dDOI Listing
October 2017

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.

Chemistry 2017 Dec 14;23(68):17384-17392. Epub 2017 Nov 14.

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

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. In this combined experimental and theoretical study, original data allowing the characterization of S⋅⋅⋅O chalcogen bonds is obtained by studying the 1:1 molecular complexes between 2,2,4,4-tetrafluoro-1,3-dithiethane (C F S ) and dimethyl ether (DME). Ab initio calculations of the C F S ⋅DME dimer yield two stable chalcogen-bonded isomers, the difference being the presence or absence of secondary F⋅⋅⋅H interactions. Liquid-krypton solutions containing C F S and DME were studied using FTIR and Raman spectroscopy. Upon subtraction of rescaled monomer spectra, clear complex bands are observed. The observed complexation shifts agree favourably with the ab initio calculated shifts of the chalcogen-bonded complexes. The 1:1 stoichiometry of the complex is confirmed and a complexation enthalpy of -13.5(1) kJ mol is found, which is in good agreement with the calculated values. A Ziegler-Rauk energy decomposition analysis revealed that electrostatic interactions prominently dominate over orbital interactions. Nevertheless, significant charge transfer occurs from the oxygen in DME to one of the sulfur atoms in C F S and the carbon along the extension of the chalcogen bond.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.201704406DOI Listing
December 2017

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

J Phys Chem A 2017 Jun 18;121(21):4180-4188. Epub 2017 May 18.

Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, 2020 Antwerp, Belgium.

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. For the mixtures containing fluoroiodomethane and dimethyl ether a hydrogen-bonded complex with an experimental complexation enthalpy of -7.0(2) kJ mol is identified. Only a single weak spectral feature is observed which can be tentatively assigned to the halogen-bonded complex. For the mixtures involving trimethylamine, both halogen- and hydrogen-bonded complexes are observed, the experimental complexation enthalpies being -12.5(1) and -9.6(2) kJ mol respectively. To evaluate the influence of fluorination on the competition between halogen and hydrogen bonding, the results obtained for fluoroiodomethane are compared with those of a previous study involving difluoroiodomethane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.7b03206DOI Listing
June 2017

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

Acta Crystallogr B Struct Sci Cryst Eng Mater 2017 Apr 14;73(Pt 2):168-178. Epub 2017 Mar 14.

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, Antwerp, 2020, Belgium.

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. Also for solutions containing chloromethane, evidence of the formation of binary associations is found, but no definitive assignment of the multiple complex bands could be made. Using van't Hoff plots, the experimental complexation enthalpies for the halogen- and hydrogen-bonded complex of difluoroiodomethane with trimethylphosphine are determined to be -15.4 (4) and -10.5 (3) kJ mol, respectively, while for the halogen- and hydrogen-bonded complexes with dimethyl sulfide, the values are -11.3 (5) and -7.7 (6) kJ mol, respectively. The experimental observation that for both trimethylphospine and dimethyl sulfide the halogen-bonded complex is more stable than the hydrogen-bonded complex supports the finding that softer Lewis bases tend to favor iodine halogen bonding over hydrogen bonding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2052520617001354DOI Listing
April 2017

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

Spectrochim Acta A Mol Biomol Spectrosc 2017 Jan 27;171:60-71. Epub 2016 Jul 27.

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. Electronic address:

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. The dataset for dimethyl ether is used to validate a numerical method based on least-squares fitting of a model including contributions of both monomers and a heterodimer with 1:1 stoichiometry. The resulting monomer and dimer spectra show excellent agreement with previous studies found in literature. The analysis of the dataset for acetone requires an extension of the model with contributions for the acetone homodimer and for (acetone)·CFX and acetone·(CFX) trimers. The results show that many signals for acetone·CFI and (acetone)·CFI are observed, while only a few bands due to acetone·(CFI) occur. The use of numerical approaches adjusted to the specificities of a mixture of two compounds allows to reliably resolve overlapping spectra of monomers and heterocomplexes and characterizing heterocomplex features that could not be deduced using earlier methods. To support the assignments made, ab initio calculations predicting geometries, relative stabilities and harmonic vibrational frequencies for the species envisaged are performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.saa.2016.07.036DOI Listing
January 2017

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.

Analyst 2016 Jun;141(13):4044-54

Biomolecular & Analytical Mass Spectrometry group, Department of Chemistry, University of Antwerp, Antwerp, Belgium. and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK and School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, UK.

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. The origin of multiple drift times is thought to be the result of protonation site isomers ('protomers'). Although some important properties of protomers have been highlighted by other studies, correlating the experimental collision cross-sections (CCSs) with calculated values has proven to be a major difficulty. As a model, this study uses the pharmaceutical compound melphalan and a number of related molecules with alternative (gas-phase) protonation sites. Our study combines density functional theory (DFT) calculations with modified MobCal methods (e.g. nitrogen-based Trajectory Method algorithm) for the calculation of theoretical CCS values. Calculated structures can be linked to experimentally observed signals, and a strong correlation is found between the difference of the calculated dipole moments of the protomer pairs and their experimental CCS separation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5an02456kDOI Listing
June 2016

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen.

Beilstein J Org Chem 2016 27;12:144-53. Epub 2016 Jan 27.

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.

The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP-MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3762/bjoc.12.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734388PMC
February 2016

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

J Phys Chem A 2016 Jul 4;120(27):4939-43. Epub 2016 Feb 4.

Dipartimento di Chimica "G. Ciamician" dell'Università , Via Selmi 2, I-40126 Bologna, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.5b12571DOI Listing
July 2016

Self-Associating Behavior of Acetone in Liquid Krypton.

J Phys Chem A 2016 Feb 3;120(6):884-94. Epub 2016 Feb 3.

Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, 2020 Antwerp, Belgium.

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. Overlapping monomer and dimer spectra are separated by analyzing the obtained data sets with numerical methods based on least-squares fitting. Although acetone is known to self-associate, only a few spectral features have been presented in literature before. In this study, the application of new numerical approaches succeeds in resolving overlapping spectra and allows observing isolated acetone dimer absorption bands for the complete mid infrared spectrum. By use of data sets of spectra recorded at temperatures between 134 and 142 K, the experimental standard dimerization enthalpy was determined to be -10.8 kJ mol(-1). MP2/aug-cc-pVDZ calculations predicted a stacked and planar dimer geometry of which the stacked geometry is more stable. Combining MP2 energies and single point corrections involving CCSD(T) calculations and complete basis set extrapolations based on the MP2/aug-cc-pVDZ equilibrium geometry lead to complexation energy of -28.4 kJ mol(-1) for the stacked geometry and -15.1 kJ mol(-1) for the planar geometry. The corresponding values for the complexation enthalpies in solution, obtained by combining these values with corrections for thermal and solvent influences are -13.7 and -5.8 kJ mol(-1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.5b10405DOI Listing
February 2016

Stereochemistry of the Brivaracetam Diastereoisomers.

Chirality 2016 Mar 6;28(3):215-25. Epub 2016 Jan 6.

UCB Pharma, Braine-L'Alleud, Belgium.

The stereochemistry of all four stereoisomers of brivaracetam was determined using vibrational circular dichroism (VCD) spectroscopy. By comparing experimentally obtained VCD spectra and computationally simulated ones, the absolute configurations can be confidently assigned without prior knowledge of their relative stereochemistry. Neither the corrected mean absolute errors analysis of the nuclear magnetic resonance (NMR) data, nor the matching of experimental and calculated infrared spectra allowed the diastereoisomers to be distinguished. VCD spectroscopy itself suffices to establish the absolute configurations of all diastereoisomers. The relative stereochemistry could also be statistically confirmed by matching experimental and computed NMR spectra using the CP3 algorithm. The combination of VCD and NMR is recommended for molecules bearing more than one chiral center, as the relative configurations obtained from NMR serve as an independent check for those established with VCD. Analysis of the calculated VCD spectra reveals that the localized NH2 scissoring mode at around 1600 cm(-1) is characteristic for intramolecular hydrogen bonding, while the orientation of the ethyl group is reflected by the delocalized modes between 1150 and 1050 cm(-1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chir.22558DOI Listing
March 2016

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

Chem Sci 2016 Jan 29;7(1):346-357. Epub 2015 Sep 29.

Department of Chemistry , University of Antwerp , Groenenborgerlaan 171 , B-2020 Antwerp , Belgium . Email:

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. For substrate and acid concentration, saturation kinetics due to O mass transfer limitation were observed. The occurrence of mass transfer limitation was further confirmed by examining the effect of the stirring rate on the initial reaction rate. Interestingly, the effect of the concentration of the catalyst on the rate shows that higher loadings result in a maximal initial rate, followed initially by a steady decrease and subsequently a rate plateau when the concentration is increased further. Mass transfer limitation and increased concentration of dinuclear catalytically active species rationalizes this hitherto unprecedented rate behavior. Continuous-wave and pulsed electron paramagnetic resonance methods were used to characterize the catalytic species present in the solution during the reaction and confirmed the presence of both mono- and dinuclear copper species. Analysis of a diverse substrate scope points towards imine-enamine tautomerization as a crucial process in the oxidation reaction. DFT calculations of these equilibrium constants (p) provided us with a qualitative tool to predict whether or not a substrate is viable for oxidation under the reaction conditions developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5sc03530aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952523PMC
January 2016

Circularly Polarized Luminescence from Helically Chiral N,N,O,O-Boron-Chelated Dipyrromethenes.

Chemistry 2016 Jan 30;22(1):93-6. Epub 2015 Nov 30.

School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU (UK).

Helically chiral N,N,O,O-boron chelated dipyrromethenes showed solution-phase circularly polarized luminescence (CPL) in the red region of the visible spectrum (λem (max) from 621 to 663 nm). The parent dipyrromethene is desymmetrised through O chelation of boron by the 3,5-ortho-phenolic substituents, inducing a helical chirality in the fluorophore. The combination of high luminescence dissymmetry factors (|glum | up to 4.7 ×10(-3) ) and fluorescence quantum yields (ΦF up to 0.73) gave exceptionally efficient circularly polarized red emission from these simple small organic fluorophores, enabling future application in CPL-based bioimaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.201504484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736443PMC
January 2016

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

Spectrochim Acta A Mol Biomol Spectrosc 2016 Feb 23;154:89-97. Epub 2015 Oct 23.

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. Electronic address:

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. The compensation effects are corrected for by carefully analyzing, using AIC and BIC information criteria, the differences observed between consecutive fittings when the degree of the polynomial model is systematically increased, and by introducing constraints prohibiting negative absorbances to occur for the monomer or for one of the oligomers. The method developed should allow other, more complicated self-associating systems to be analyzed with a much higher accuracy than before.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.saa.2015.10.012DOI Listing
February 2016

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

J Phys Chem A 2015 Nov 13;119(47):11532-47. Epub 2015 Nov 13.

Department of Chemistry, University of Missouri-Kansas City , Kansas City, Missouri 64110, United States.

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. Additionally, the variable temperature (-153 to -133 °C) studies of the Raman spectra of the sample dissolved in krypton have been recorded. The enthalpy difference between the trans and gauche conformers in xenon solutions has been determined to be 109 ± 15 cm(-1) (1.47 ± 0.16 kJ mol(-1)), and in krypton solution, the enthalpy difference has been determined to be 97 ± 16 cm(-1) (1.16 ± 0.19 kJ mol(-1)) with the trans conformer as the more stable form. Approximately 46 ± 2% of the trans form is present at ambient temperature. By utilizing the microwave rotational constants of five isotopologues for trans and the structural parameters predicted from MP2(full)/6-311+G(d,p) calculations, adjusted r0 parameters have been obtained for trans conformer. The r0 structural parameter values for the trans form are for the heavy atom distances (Å): Si-F = 1.608 (3); C-Cl = 1.771 (3); Si-C = 1.884 (3); and angles (deg): ∠FSiC = 108.9 (5); ∠ClCSi = 104.9 (5). The results are discussed and compared to some related molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.5b06679DOI Listing
November 2015

Elucidation of the absolute configuration of rhizopine by chiral supercritical fluid chromatography and vibrational circular dichroism.

J Sep Sci 2015 Jul 7;38(14):2545-50. Epub 2015 Jul 7.

Research Institute for Chromatography (R.I.C.), Kortrijk, Belgium.

The absolute configuration of rhizopine, an opine-like natural product present in nitrogen-fixing nodules of alfalfa infected by rhizobia, is elucidated using a combination of state-of-the-art analytical and semi-preparative supercritical fluid chromatography and vibrational circular dichroism spectroscopy. A synthetic peracetylated racemate was fractionated into its enantiomers and subjected to absolute configuration analysis revealing that natural rhizopine exists as a single enantiomer. The stereochemistry of non-derivatized natural rhizopine corresponds to (1R,2S,3R,4R,5S,6R)-4-amino-6-methoxycyclohexane-1,2,3,5-tetraol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.201500138DOI Listing
July 2015

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

J Phys Chem A 2015 Jun 14;119(22):5597-606. Epub 2015 May 14.

†Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.

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. This region, often denoted as a σ-hole, allows the molecules to interact with Lewis bases and form a halogen bond. To experimentally characterize the competition between both these noncovalent interactions, Fourier transform infrared and Raman spectra of liquefied noble gas solutions containing perfluorohalogenated ethylene derivatives (C2F3X; X = F, Cl, Br, or I) and trimethylamine(-d9) were investigated. Analysis of the spectra shows that in mixed solutions of trimethylamine(-d9) and C2F4 or C2F3Cl lone pair···π complex is present, while evidence for halogen-bonded complex is found in solutions containing trimethylamine(-d9) and C2F3Cl, C2F3Br, or C2F3I. For all species observed, complexation enthalpies were determined, the values varying between -4.9(1) and -24.4 kJ mol(-1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.5b02283DOI Listing
June 2015

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

J Org Chem 2015 Apr 17;80(7):3359-67. Epub 2015 Mar 17.

§Department of Chemistry, Imperial College London South Kensington Campus, London SW7 2AZ, United Kingdom.

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. Despite a low amount of available material and a relatively unusual example of using VCD carbonyl multiplets, the absolute configuration could be reliably predicted, strengthening the case for application of VCD in the study of complex natural products. Spectral and crystallographic evidence for or against the formation of a dimeric aggregate is discussed; in solution, the VCD spectra strongly suggest only monomeric species are present.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jo5022647DOI Listing
April 2015

Infrared and Raman measurements of halogen bonding in cryogenic solutions.

Authors:
Wouter Herrebout

Top Curr Chem 2015 ;358:79-154

Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium,

Because they create a weakly interacting environment which, combined with the low temperatures used, leads to small bandwidths and thus facilitates the detection of complex bands only slightly shifted from the monomer modes, solutions in liquefied inert gases have proven to be an ideal medium to study molecular complexes held together by weak and medium-strong C-X…Y (with X=I, Br, Cl and Y=O, N, S, F, Cl, π,…) halogen bonds. In this chapter, experimental setups for infrared and Raman study of cryosolutions are described, and general methodologies used to examine weakly bound molecular complexes are discussed. The methods are illustrated using data obtained for a variety of halogen-bonded complexes involving, amongst others, the trifluorohalomethanes CF3Cl, CF3Br, and CF3I, and a variety of Lewis bases. The results are compared with theoretical data obtained from ab initio calculations, and with experimental and theoretical data obtained for complexes involving weak C-H proton donors such as CHF3. Preliminary data for mixed proton donor/halogen donors such as CHClF2, CHBrF2 are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/128_2014_559DOI Listing
June 2015

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

Phys Chem Chem Phys 2015 Mar;17(12):7694-8

Dipartimento di Chimica "G. Ciamician" dell'Università, Via Selmi 2, I-40126 Bologna, Italy.

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. The nuclear hyperfine structure due to the quadrupole coupling effects of (35)Cl/(37)Cl and (14)N nuclei has been fully resolved. The (14)N quadrupole coupling constants allow estimating the effective orientation of NH3 in the complex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c4cp05167jDOI Listing
March 2015