Wlodzimierz Ciesielski

Computed and Experimental Chemical Shift Parameters for Rigid and Flexible YAF Peptides in the Solid State

DFT methods were employed to compute the (13)C NMR chemical shift tensor (CST) parameters for crystals of YAF peptides (Tyr-Ala-Phe) with different stereochemistry for the Ala residue. Tyr-D-Ala-Phe 1 crystallizes in the C2 space group while Tyr-L-Ala-Phe crystallizes in either the P2(1)2(1)2 space group (2a) or the P6(5) space group (2b). PISEMA MAS measurements for samples with a natural abundance of (1)H and (13)C nuclei and (2)H QUADECHO experiments for samples with deuterium labeled aromatic rings were used to analyze the geometry and time scale of the molecular motion. At ambient temperature, the tyrosine ring of sample 1 is rigid and the phenylalanine ring undergoes a π-jump, both rings in sample 2a are static, and both rings in sample 2b undergo a fast regime exchange. The theoretical values of the CST were obtained for isolated molecules (IM) and clusters employing the ONIOM approach. The experimental (13)C δ(ii) parameters for all of the samples were measured via a 2D PASS sequence. Significant scatter of the computed versus the experimental (13)C CST parameters was observed for 1 and 2b, while the observed correlation was very good for 2a. In this report, we show that the quality of the (13)C σ(ii)/(13)C δ(ii) correlations, when properly interpreted, can be a source of important information about local molecular motions.

Complementarity of solvent-free MALDI TOF and solid-state NMR spectroscopy in spectral analysis of polylactides.

We report systematic studies of solvent-free modification of matrix-assisted laser desorption/ionization time-of-flight (SF MALDI-TOF) mass spectrometry in analysis of synthetic polymers employing solid-state NMR spectroscopy as a supporting technique. In the present work oligomeric (M(n) = 4000 g mol(-1)) poly(L-lactide) (PLLA) was employed as a reference sample. The analyte was embedded into four matrixes commonly used in MALDI-TOF analysis of polymers: 1,8-dihydroxy-9-anthracenone (DT), 2,5-dihydroxybenzoic acid (DHB), 2-(4 hydroxyphenylazo)-benzoic acid (HABA), and trans-3-indoleacrylic acid (IAA). Solid-state NMR measurements clearly showed that the initial crystallinity of PLLA had no influence on quality of SF MALDI-TOF spectra since the crystalline structure of the analyte was not preserved during analyte/matrix grinding. Interestingly, the matrix remained crystalline during the samples preparation. It was also found that, on the contrary to the dried droplet (DD) method, the SF approach leads to highly resolved mass spectra for a large variety of matrixes. Finally, problems of polymorphism and mechanochemical processes that can occur during the analyte/matrix grinding are briefly discussed.

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.

Anisotropy of chemical shift and J coupling for P-31 and Se-77 in trimethyl and triphenyl phosphine selenides

The 31P and 77Se magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments for selenium-77 enriched (70%) trimethylphosphine selenide 1 and triphenylphosphine selenide 2 were carried out in order to determine the nuclear magnetic shielding tensors of both nuclei and to establish values of the phosphorus-selenium indirect spin-spin coupling anisotropy delta J. The m = +1/2 and m = -1/2 subspectra were analysed by the dipolar-splitting-ratio method of Eichele and Wasylischen. For the C(S) molecule 1, delta J was obtained to be +640 +/- 260 Hz from the 31P spectrum and +550 +/- 140 Hz from the 77Se spectrum. Density functional theory (DFT) calculations give a delta J value of about +705 Hz. The value of delta J could not be determined unambiguously by analysis of the 31P spectra for the C1 molecules 2; nevertheless, an estimation of delta J was possible. The principal axis 3 of the phosphorus shielding tensor was determined to be nearly parallel to the PSe bond in 1 and 2. For the selenium shielding of 1, the same orientation was found, whereas in 2, the principal axis 2 of the selenium shielding was found to be oriented nearly along the PSe bond. The experimentally determined phosphorus nuclear magnetic shielding tensors agree well with those calculated by the IGLO method. For those two principal values of the selenium-shielding tensors corresponding to directions nearly perpendicular to the SeP bond, the agreement between calculated and experimental values is satisfactory. For the third one, corresponding to the principal axis close to the SeP bond, the calculated deshielding contributions are distinctly too small for both compounds investigated. Trends observed for the calculated molecular orbital (MO) contributions to the shielding as well as possible reasons for the underestimation of the deshielding contributions along the SeP bond are discussed.

Application of ionic liquid matrices in spectral analysis of poly(lactide) - solid state NMR spectroscopy versus matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry

The work presented here shows the complementarity of Solid State NMR (SS NMR) spectroscopy and Matrix-Assisted Laser Desorption/Ionization-time-of-flight (MALDI-TOF) mass spectrometry in spectral analysis of poly(L-lactide) (PLLA) using second-generation ionic liquid matrices (ILM II) prepared from N,N-diisopropylethylamine (DEA) and DHB (2,5-dihydroxybenzoic acid), IAA (3-indoleacrylic acid), and HABA (2-(4-hydroxyphenylazo) benzoic acid). The 13C cross-polarization (CP) magic angle spinning (CP/MAS) SS NMR technique was used to study the structure of ionic liquid matrices, their thermal stability, and the influence of ILM on the morphology of polymer. A comparison of MALDI-TOF spectra for samples prepared employing the dried droplet (DD) and the solvent free (SF) mode showed that the former approach gave better results (signal to noise ratio) very likely due to intimate contact between analyte and matrix domains. This hypothesis was verified by analysis of CP build-up curves for DHB–DEA–PLLA samples prepared employing both methods. We also showed that an alternative method of sample preparation based on the melting of ILM II together with a suspended polymer in the liquid matrix is unsatisfactory, particularly for those matrices which can undergo isomerization at higher temperatures (e.g., HABA–DEA and IAA–DEA).

The influence of the stereochemistry of alanine residue on the solid state conformation and crystal packing of opioid peptides containing D-Ala or L-Ala in message domain--XRD and NMR study.

In this work, an X-ray diffraction (XRD) and solid state NMR study of two tetrapeptides with different stereochemistry of alanine residue is presented using Tyr-(D-Ala)-Phe-Gly (1), an N-terminal sequence of opioid peptide dermorphin, and its biologically inactive analog Tyr-(L-Ala)-Phe-Gly (2). Single-crystal XRD proved that 1 crystallized under different conditions from exclusively one structure: a monoclinic crystal with P2(1) space group. In contrast, 2 very easily formed at least three crystallographic modifications, 2a (monoclinic P2(1)), 2b (orthorhombic P2(1)2(1)2) and 2c (tetragonal P4(1)2(1)2). Solid-state NMR spectroscopy was employed to investigate the structure and molecular dynamics of 1, 2a, and 2b. By employing different NMR experiments (dipolar dephasing and PILGRIM) and an analysis of the (13)C principal elements of the chemical shift tensor (CST), it was proven that the main skeleton of tetrapeptides is rigid, whereas significant differences in the molecular motion of the aromatic residues were observed. Comparing current data with those of previous studies (J. Phys. Chem. B2004, 108, 4535-4545 and Cryst. Growth Des. 2009, 9, 4050-4059), it can be assumed that an important preorganization mechanism anticipating the formation of peptide crystals containing D-Ala in sequence is the intramolecular CH-π interaction, which occurs for the amino acid with D stereochemistry. This effect may be responsible for the formation of only one crystallographic form of D-Ala peptides.

A new method for distinguishing between enantiomers and racemates and assignment of enantiomeric purity by means of solid-state NMR. Examples from oxazaphosphorinanes.

It is shown that enantiomers and racemates that have identical isotropic NMR chemical shift as well as anisotropic chemical-shift tensor parameters can be easily distinguished by means of the ODESSA (One Dimensional Exchange Spectroscopy by Sideband Alternation) technique. The method is based on the fact that the molecular symmetries and packing of enantiomers and racemates are usually significantly different. The power of the proposed approach is demonstrated by employing as model compounds P-chiral oxazaphosphorine derivatives, which are widely used in clinical oncology. Correlation of the amplitude of the ODESSA decay (AOD) with enantiomeric excess is also presented.

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 precise tool for assigning the tautomeric form and proton position in the intramolecular bridges of o-hydroxy Schiff bases.

Two analogous Schiff bases, (S,E)-2-((1-hydroxy-3-methyl-1,1-diphenylbutan-2-ylimino)methyl)phenol (1) and (S,Z)-2-hydroxy-6-((1-hydroxy-3-methyl-1,1-diphenylbutan-2-ylamino)methylene)cyclohexa-2,4-dienone (2), exist in the solid state as phenol-imine and keto-amine tautomers, respectively. Their crystal structures were solved using the X-ray diffraction method. Sample 1 forms orthorhombic crystals of space group P2(1)2(1)2(1), while 2 forms monoclinic crystals of space group P2(1). In each sample, one molecule is in the asymmetric unit of the crystal structure. One-dimensional and two-dimensional solid state NMR techniques were used for structure assignment and for inspection of the (13)C and (15)N δ(ii) of the chemical shift tensor (CST) values. NMR study indicates that the span (Ω = δ(11)-δ(33)) and the skew (κ = 3(δ(22)-δ(iso)/Ω) are extremely sensitive to change in the tautomeric form of the Schiff bases. Theoretical calculations of NMR shielding parameters for 1 and 2 and a model compound with reduced aliphatic residue were performed using the GIAO method with B3LYP functional and 6-311++g(d,p) basis sets. From comparative analysis of the experimental and theoretical parameters, it was concluded that the position of hydrogen in the intramolecular bridge has tremendous influence on (13)C and (15)N CST parameters. Inspection of Ω and κ parameters allowed for the establishment of the nature of the hydrogen bonding and the assignment of the equilibrium proton position in the intramolecular bridges in the solid state.

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.