Sebastian Olejniczak

Structural studies of N-(2′-substituted phenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximides by X-ray diffraction and NMR spectroscopy—proofs for CH/π interactions in liquid and solid phases

N-(2′-R-Phenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximides with R = Me (1), OMe (2), OEt (3) and H (4) were investigated. The crystal and molecular structures of 1–3, determined by single crystal methods, show different conformations of the N-(2′-R-phenyl) group. Anti conformations and weak intermolecular CH/π contacts were found in 2 and 3, while anti and syn conformations coexist in 1 with CH/π contacts being absent. Solid-state 13C CP/MAS spectra confirm the X-ray molecular structural data. Two crystallographically independent molecules in the unit cell of 2 correspond to two isotropic chemical shifts for C atoms in the CP/MAS spectrum. The different molecular dynamics of both molecules in the crystal lattice of 2 indicated by the thermal factors and intermolecular CH/π contacts were clearly visible in different cross-polarisation profiles. The NMR data of 4 suggest that the phenyl ring bonded to the nitrogen is nearly coplanar to the ethanocarboximide ring. Full assignment of liquid state 1H and 13C NMR spectra of 1–4 was possible by application of high field NMR spectroscopy. Some incorrect assignments of 13C chemical shifts in the literature were revised. The different ratios of [syn]∶[anti] in solutions of chloroform and DMSO are explained in terms of different intermolecular CH/π interactions.

Alkylation of thymine with 1,2-dibromoethane

Abstract Alkylation of thymine with 1,2-dibromoethane depends strongly on the reaction conditions. Various alkyl derivatives may be produced, including N-1- or N-3-monosubstituted alkylthymines and products of their cyclisation, as well higher molecular weight products resulting from intermolecular substitution of N-1- and N-3-mono- and N-1,N-3-dialkylthymines. We have identified two cyclic products 5 and 6 and the dialkylated derivative 7, for which detailed structural analyses have been performed.

15N and 13C High-Resolution Solid-State NMR Study of the Polymorphism of the L-Enantiomer of N-Benzoylphenylalanine

In this paper, several approaches which allow the investigation of mixtures of polymorphs, employing modern solid-state NMR (SS NMR) spectroscopy are reported. A convenient methodology for characterization of the hydrogen bonding and molecular conformation of a polymorphic sample by means of one-dimensional and two-dimensional, 13C and 15N NMR experiments as well as CSA tensor analysis and theoretical calculations is presented. Two-dimensional heteronuclear SS NMR allowed definition of the polymorphic domain of N-benzoyl-L-phenylalanine (N-Bz-Phe). The graphical method of Herzfeld and Berger was used to measure the 13C and 15N spinning sideband intensities which allowed the calculation of NMR parameters for labeled centers of N-Bz-Phe. The experimental data were compared with computed results obtained by means of the DFT hybrid method with B3PW91 functional and 6-311++G** basis set.

Solid State NMR Study and Density Functional Theory (DFT) Calculations of Structure and Dynamics of Poly(p-xylylenes)

High resolution solid state (13)C nuclear magnetic resonance (SS NMR) measurements were carried out on poly(p-xylylene) (PPX). The samples comprised vapor-deposited specimens as well as pure alpha and beta polymorphs of this polymer. The measurements were performed using cross-polarization and magic angle spinning (CP/MAS) techniques. Density functional theory gauge-including-atomic-orbital (DFT GIAO) calculations of NMR shielding parameters (13)C sigma(ii) were performed for the optimized geometry and structure of a xylylene trimer, acquired from the X-ray data, including intermolecular interactions. Two-dimensional phase adjusted spinning sideband (2D PASS) correlation was employed for the assignment of the values of the principal elements (13)C delta(ii) of the chemical shift tensor (CST). A comparative analysis of shielding (sigma(ii)) versus chemical shift (delta(ii)) parameters showed substantial differences between the molecular dynamics of alpha and beta polymorphs. This observation was further supported by the measurements of (13)C T(1) relaxation times and the analysis of cross-polarization kinetics. Frequency switched Lee-Goldburg heteronuclear correlation (FSLG HETCOR) for the (1)H-(13)C system was used in order to analyze molecular packing in both polymorphs. As a result of all of the above measurements, new insight into the mechanism of thermal phase transition from the alpha to the beta polymorph of poly(p-xylylene) is presented.

Solid-state NMR spectroscopy as a tool supporting optimization of MALDI-TOF MS analysis of polylactides

We report systematic structural studies of poly(l-lactide) (PLLA) employing matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and solid-state NMR spectroscopy. 13C cross polarization magic angle spinning (CP/MAS) NMR data for 1,8-dihydroxy-9-anthracenone (DT), 2,5-dihydroxybenzoic acid (DHB), 2-(4-hydroxyphenylazo)-benzoic acid (HABA), and trans-3-indoleacrylic acid (IAA), four matrices commonly used in MALDI-TOF analysis of polymers, were analyzed to test the influence of crystallization conditions (solvent, inorganic salt) on sample morphology. 13C principal elements of chemical shift tensor (CST) and line-shape analyses were employed to study of the nature of hydrogen bonding and to evaluate the crystallinity and amorphicity of the pure polymer. NMR parameters for PLLA were compared with data for polylactide crystallized with the four matrices under different conditions with the addition of two inorganic salts as cationization agents. This study revealed that the semicrystalline structure of the polymer does not change when it is embedded in the matrix.

Investigation of structure and motional behavior of 1,6:3,4-dianhydro-2-O-tosyl-β-d-galactopyranose in solution by means of multiple-field NMR spectroscopy

Abstract In this paper 1H NMR, density functional theory gauge invariant atomic orbital (DFT GIAO) calculation of proton shielding NMR parameters and multi-field, carbon-13 relaxation data for 1,6:3,4-dianhydro-2-O-tosyl-β- d -galactopyranose (1) are reported. From 1H NMR measurements, carried out in three solvents (chloroform, benzene and dimethylosulfoxide), it is apparent that the observed shifting of 1H resonances, among the other factors, is caused by an aromatic ring current effect related to different orientations of the tosyl group with respect to the sugar ring. DFT GIAO calculations are applied for analyzing the changes of 1H shielding parameters in relation to geometry of the compound 1. The relaxation of the quaternary carbons of tosyl group which relax via CSA mechanism is used to establish the mode of local motion. In the complementary approach, employing the 1H chemical shift, dynamic parameters analysis, as well as results from theoretical calculations, the changes of the geometry of 1 in different environments are deduced.

Elucidation of structural restraints for phosphate residues with different hydrogen bonding and ionization states.

Solid state NMR spectroscopy and gauge including atomic orbital (GIAO) theoretical calculations were employed to establish structural restraints (ionization, hydrogen bonding, spatial arrangement) for O-phosphorylated l-threonine derivatives in different ionization states and hydrogen bonding strengths. These structural restraints are invaluable in molecular modeling and docking procedures for biological species containing phosphoryl groups. Both the experimental and the GIAO approach show that 31P delta ii chemical shift tensor parameters are very sensitive to the ionization state. The negative values found for the skew kappa are typical for -2 phosphates. The distinct span Omega values reflect the change of strength of hydrogen bonding. For species in the -1 ionization state, engaged in very strong hydrogen bonds, Omega is smaller than for a phosphate group involved in weak hydrogen bonding. For phosphates in the -2 ionization state, Omega is significantly smaller compared to -1 species, although the kappa for -1 samples never reaches negative values. For -1 phosphate residues, in the case when 1H one pulse and/or combined rotation and multiple pulse spectroscopy (CRAMPS) sequences fail and assignment of proton chemical shift is ambiguous, a combination of 1H-(13)C and 1H-(31)P 2D heteronuclear correlation (HETCOR) correlations is found to be an excellent tool for the elucidation of 1H isotropic chemical shifts. In addition, a 2D strategy using 1H-(1)H double quantum filter (DQF) correlations [a back-to-back (BABA) sequence in this work] is useful for analyzing the topology of hydrogen bonding. In the case of a multicenter phosphorus domain, 2D 31P-(31)P proton driven spin diffusion experiments give information about the spatial arrangement of the phosphate residues.

Structural studies of 2-(3′,4′-dihydroxyphenyl)-7-β-D-glucopyranos-1-O-yl-8-hydroxychroman-4-one in the liquid and solid states by means of 2D NMR spectroscopy and DFT calculations

Homo- and heteronuclear correlated spectroscopy in the liquid phase and the PASS-2D NMR technique in the solid state were applied to the identification and structural studies of the flavanone 2-(3′,4′-dihydroxyphenyl)-7-β-D-glucopyranos-1-O-yl-8-hydroxychroman-4-one 1. The principal elements of the 13C chemical shift tensor were established and verified by DFT GIAO calculations. Analysis of the 13C δii and comparison with the theoretical shielding parameters calculated for different conformers of 1 in a vacuum were carried out to choose the most reliable geometry in the solid state.

13C high-resolution solid state NMR studies of the structure and dynamics of 1,6:3,4-dianhydro-2-O-tosyl-β-d-galactopyranose

13C CP/MAS, dipolar dephasing MAS and theoretical GIAO calculations were employed to assign 13C resonances to the molecular structure of 1,6:3,4-dianhydro-2-O-tosyl-beta-D-galactopyranose 1. From spinning sideband intensities, employing the graphical method of Herzfeld and Berger the 13C delta(ii) parameters for aromatic residue were calculated. The experimental data were compared with computed results obtained by means of the B3PW91 hybrid method and 6-311G (df, p) basis set. The X-ray geometry of 1 with the correlated position of hydrogen atoms was taken as input data for theoretical calculations. As concluded from Cambridge Crystallographic Database (CSD) search, there are two reports describing the X-ray studies of 1 that show the slightly different geometry of the compound under investigation. This work shows that such discrepancies in geometry can generate differences between computed 13C delta(ii) parameters up to 6 ppm. 13C T1 and 1H T1rho relaxation times reveal that 1 is very rigid in crystal lattice. This structure is characterized by extremely long 1H T1rho, found to be in range ca. 200 ms.

Synthesis and Structural Studies ofSP andRP Diastereomers of Deoxyxylothymidyl-3′-O-acetylthymidyl (3′,5′)-O-(2-Cyanoethyl)phosphorothioate in Solution and in the Solid State

The synthesis and full assignment of the molecular structure of the diastereomers of deoxyxylothymidyl-3′-O-acetylthymidyl (3′,5′)-O-(2-cyanoethyl)phosphorothioate (1) in the liquid phase based on 1 H, 13C, 1D and 2D homo- and heteronuclear PFG (Pulse Field Gradient) NMR spectroscopic experiments are reported. The pseudorotation parameters of deoxyribose and deoxyxylose were analyzed by means of the PSEUROT program. The absolute configuration RP and SP of the phosphorus centers was deduced from 1H ROESY experiment. The 31P CP/MAS technique was used to establish the ratio between the amorphous and crystalline phases, and to test the progress of crystallization. The differences in the 31P δii principal elements of the chemical shift tensor, in particular the δ33 parameter, for crystalline and amorphous phases were calculated. Finally, the X-ray data for the SP diastereomer are reported. The influence of weak C−H···S hydrogen bonding on the molecular packing of both Rp-1 and SP-1, and the significance of this type of intermolecular interaction for phosphorothioate systems is discussed.