Marek J. Potrzebowski

Study of Intermolecular Interactions in the Corrole Matrix by Solid‐State NMR under 100 kHz MAS and Theoretical Calculations

Recent progress in solid-state (SS)NMR spectroscopic methods based on fast magic angle spinning (MAS) has enabled new opportunities for the structural study of small quantities (< 5 mg) of natural abundance samples. Utilizing throughspace and through-bond polarization transfer, indirect detection of low-g nuclei, and suitable homoand heteronuclear decoupling, oneand two-dimensional (1D and 2D) spectra of such samples can be measured with excellent sensitivity and resolution. However, determination of the short-range intermolecular order often remains elusive. Such analyses can be well-served by studying heteronuclear correlations that take advantage of the large chemical shift range of most low-g nuclei (for example, C or N). Indeed, heteronuclear correlation (HETCOR) NMR spectroscopy and measurements of internuclear distances, often in concert with theoretical calculations, have provided structural details of complex hydrogen-bonded systems in chemistry and biology, blended materials, and host–guest pairs. Still, intermolecular polarization transfers to low-g nuclei are often hampered by low sensitivity. A promising solution to this challenge is offered by homonuclear H–H 2D correlation methods, such as double-quantum (DQ)MAS or spin-diffusion (NOESYlike) experiments, provided that sufficient resolution is achieved in both dimensions. One of the possible approaches is the use of H CRAMPS decoupling in concert with fast MAS to boost resolution in these experiments. The recent development of ultrafast MAS (at 100 kHz and more) provides access to appropriate H resolution without RF decoupling. Herein, we report the first application of H 2D SSNMR measurements under MAS at 100 kHz, which are used in combination with indirectly detected H{C} and H{N} HETCOR experiments and theoretical calculations to scrutinize the interactions within a host–guest (HG) system consisting of 5,10,15-tris(pentafluorophenyl)corrole 1, and toluene (Scheme 1).

Ruthenium Carbene Siloxide Complexes Immobilized on Silica: Synthesis and Catalytic Activity in Olefin Metathesis

Ruthenium alkylidene complexes, based on second generation Hoveyda–Grubbs catalysts, have been directly attached to silica through covalent Ru‐O‐Si bonds, characterized by using cross polarization magic angle spinning 13C NMR (CP MAS 13C NMR) spectroscopy, and proved active in selected metathetic transformations. The complexes can be easily recycled and subsequently reused. In the ring closing metathesis (RCM) reaction of diethyl diallyl malonate the heterogenized complex can be recycled up to 15 times.

Molecular structures and hydrogen bonding in the 1 : 1 and 1 : 2 complexes of pyridine betaine with 2,6-dichloro-4-nitrophenol; an example of strongly coupled hydrogen bonds, OH⋯OCOH⋯O−

Abstract Crystalline complexes of pyridine betaine (PBET) with one and two molecules of 2,6-dichloro-4-nitrophenol (DCNP) were prepared and characterized by single-crystal X-ray analysis and Fourier transform IR (FTIR), Raman, 13 C CP/MAS NMR and UV spectroscopies. Both complexes are monoclinic, space group P2 1 c , with Z = 4. In PBET·DCNP, the proton from DCNP is transferred to PBET and both residues are linked by an OH⋯O − hydrogen bond of length 2.419(3) A and angle 165(4)°. In PBET·(DCNP) 2 , the COOH group is engaged in two hydrogen bonds, resulting in a short OH⋯O − bond of length 2.452(4) A and angle 178(4)° and a long CO⋯HO bond of length 2.623(4) A and angle 160(6)°. The 13 C NMR spectra in the solid state show signals at 167.7 and 170.2 ppm due to the carboxyl group in PBET·DCNP and PBET·(DCNP) 2 respectively. The powdered FTIR spectrum of PBET·DCNP shows a broad absorption with a maximum at 806 cm −1 tentatively assigned to ν OH . Although in PBET·(DCNP) 2 the analogous hydrogen bond is longer than in the 1 : 1 complex, the absorption is shifted to lower wavenumbers (773 cm −1 ). The absorption due to the longer hydrogen bond is at 2832 cm −1 and is shifted towards higher wavenumbers relative to the analogous hydrogen bond in the complex of PBET with two molecules of pentachlorophenol (PBET·(PCP) 2 ; O⋯O = 2.582(6) and 2.611(6) A; ν H = 2725 cm −1 ). The observed absorption shifts suggest that, in PBET·(DCNP) 2 , the hydrogen bonds perturb each other. Two peaks near 300 and 420 nm in the UV spectra of the title complexes in acetonitrile confirm the presence of phenol and phenolate residues in equilibrium.

Simple and accurate determination of X-H distances under ultra-fast MAS NMR.

We demonstrate that a very simple experiment, Cross-Polarization with Variable Contact-time (CP-VC), is very efficient at ultra-fast MAS (νR ≥ 60 kHz) to measure accurately the C-H and N-H distances, and to analyze the dynamics of bio-molecules. This experiment can be performed with samples that are either (13)C or (15)N labeled or without any labeling. The method is very robust experimentally with respect to imperfect Hartman-Hahn setting, and presents a large scaling factor allowing a better dipolar determination, especially for long C-H or N-H distances, or for CH3 or NH3 moieties with three-site hopping. At ultra-fast MAS, it can be used quantitatively in a 2D way, because its scaling factor is then little dependent on the offsets. This robustness with respect to offset is related to the ultra-fast spinning speed, and hence to the related small rotor diameter. Indeed, these two specifications lead to efficient n = ±1 zero-quantum Hartman-Hahn CP-transfers with large RF-fields on proton and carbon or nitrogen channels, and large dipolar scaling factor.

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.

Recent progress in solid-state NMR studies of drugs confined within drug delivery systems.

Recent progress in the application of solid-state NMR (SS NMR) spectroscopy in structural studies of active pharmaceutical ingredients (APIs) embedded in different drug carriers is detailed. This article is divided into sections. The first part reports short characterization of the nanoparticles and microparticles that can be used as drug delivery systems (DDSs). The second part shows the applicability of SS NMR to study non-steroidal anti-inflammatory drugs (NSAIDs). In this section, problems related to API-DDS interactions, morphology, local molecular dynamics, nature of inter- or intramolecular connections, and pore filling are reviewed for different drug carriers (e.g. mesoporous silica nanoparticles (MSNs), cyclodextrins, polymeric matrices and others). The third and fourth sections detail the recent applications of SS NMR for searching for antibiotics and anticancer drugs confined in zeolites, MSNs, amorphous calcium phosphate and other carriers.

Ibuprofen in mesopores of Mobil Crystalline Material 41 (MCM-41): a deeper understanding.

In this work, we compared two methods (incipient wetness and melting) for the encapsulation of ibuprofen in the pores of Mobil Crystalline Material 41 (MCM-41) through NMR (nuclear magnetic resonance) spectroscopy. (1)H NMR spectra were recorded under very fast MAS (sample spinning 60 kHz) conditions in both 1D and 2D mode (NOESY sequence). We also performed (13)C cross-polarization magic angle spinning (CP/MAS) experiments, (13)C single pulse experiments (SPE), and (1)H-(13)C HSQC HR/MAS (heteronuclear single quantum coherence high resolution) HR/MAS correlations. Evaluation of the encapsulation methods included an analysis of the filling factor of the drug into the pores. The stability of Ibu/MCM in an environment of ethanol or water vapor was tested. Our study showed that melting a mixture of Ibu and MCM is a much more efficient method of confining the drug in the pores compared to incipient wetness. The optimal experiments for the former method achieved a filling factor of approximately 60%. We concluded that the major limitation to the applicability of the incipient wetness method (filling factor ca. 20%) is the high affinity of solvent (typically ethanol) for MCM-41. We found that even ethanol vapor can remove Ibu from the pores. When a sample of Ibu/MCM was stored for a few hours in a closed vessel with ethanol vapor, Ibu was transported from the pores to the outer walls of MCM. We observed a similar phenomenon with water vapor, although this process is slower compared to the analogous procedure using ethanol. Our study clearly demonstrates that existing methods used to encapsulate drugs in mesoporous silica nanoparticles (MSNs) require reevaluation.

Fine refinement of solid-state molecular structures of Leu- and Met-enkephalins by NMR crystallography.

This paper presents a methodology that allows the fine refinement of the crystal and molecular structure for compounds for which the data deposited in the crystallographic bases are of poor quality. Such species belong to the group of samples with molecular disorder. In the Cambridge Crystallographic Data Center (CCDC), there are approximately 22,000 deposited structures with an R-factor over 10. The powerful methodology we present employs crystal data for Leu-enkephalin (two crystallographic forms) with R-factor values of 14.0 and 8.9 and for Met-enkephalin (one form) with an R-factor of 10.5. NMR crystallography was employed in testing the X-ray data and the quality of the structure refinement. The GIPAW (gauge invariant projector augmented wave) method was used to optimize the coordinates of the enkephalins and to compute NMR parameters. As we reveal, this complementary approach makes it possible to generate a reasonable set of new coordinates that better correlate to real samples. This methodology is general and can be employed in the study of each compound possessing magnetically active nuclei.

Convenient synthesis of propane aminophosphonic acids, aminodiphosphonic acids and their structural analogues, mediated by azetidinium salts

Abstract The reactions of azetidinium salts with phosphorus nucleophiles R2P(O)H have been investigated. Treatment of O-benzyl-N,N-diethyl-3-hydroxyazetidinium salt 2 with R2P(O)H in the presence of sodium hydride gave the corresponding γ-N,N-diethylamino-β-benzyloxypropylphosphonate 6a or phosphine oxide 6b. After debenzylation γ-N,N-diethylamino-β-hydroxypropylphosphonate 3a and phosphine oxide 3b were obtained. The compound 6a was converted into its sulfonate ester 8 which underwent elimination to yield 4. The structure 4 has been employed in Michael addition of R2P(O)H to form compounds 5 containing two phosphorus centers. Further compounds of type 3 have been transformed into compounds 5 by reaction with R2P(O)H in the presence of 1.1 equivalents of NaH in boiling toluene. Finally, azetidinium salts 1 have been converted into compounds 5a by reaction with two equivalents of R2P(O)H in the presence of 2.1 equivalents of NaH. Molecular mechanics with implementation of the Allinger MM2 force field and semiempirical AM1 and PM3 methods were used to investigate structures 5d and 5f.

Probing molecular geometry of solids by nuclear magnetic resonance spin exchange at the n=0 rotational-resonance condition

Exploration of the molecular geometry in rotating powder solids on the basis of magnetization exchange between spins with identical isotropic chemical shifts but differing chemical shielding tensor orientations is demonstrated experimentally. For this we take advantage of the potential of the ODESSA (one-dimensional exchange spectroscopy by sidebands alternation) experiment for the accurate measurement of spin exchange rate constants. We also report the observation of oscillatory behavior of the rotor-driven magnetization exchange at this so-called n=0 rotational-resonance condition which, in contrast to n=1,2,3,… rotational-resonance conditions, takes place at nearly arbitrary magic-angle spinning frequencies. The sensitivity of the longitudinal exchange decays to the relevant physical parameters of the spin system under conditions of rotor-driven and proton-driven magnetization exchange is discussed theoretically and demonstrated experimentally. Several 13C and 31P spin-exchange measurements have been p...