Conformation analysis and molecular mobility of ethylene and tetrafluoroethylene copolymer using solid-state 19F MAS and 1H --> 19F CP/MAS NMR spectroscopy

The changes in the conformation and molecular mobility accompanied by a phase transition in the crystalline domain were analyzed for ethylene (E) and tetrafluoroethylene (TFE) copolymer, ETFE, using variable-temperature (VT) solid-state 19F magic angle spinning (MAS) and 1H --> 19F cross-polarization (CP)/MAS NMR spectroscopy. The shifts of the signals for fluorines in TFE units to higher frequency and the continuing decrease and increase in the T1rho(F) values suggest that conformational exchange motions exist in the crystalline domain between 42 and 145 degrees C. Quantum chemical calculations of magnetic shielding constants showed that the high-frequency shift of TFE units should be induced by trans to gauche conformational changes at the CH2-CF2 linkage in the E-TFE unit. Although the 19F signals of the crystalline domain are substantially overlapped with those of the amorphous domain at ambient probe temperature (68 degrees C), they were successfully distinguished by using the dipolar filter and spin-lock pulse sequences at 145 degrees C. The dipolar coupling constants for the crystalline domain, which can be estimated by fitting the dipolar oscillation behaviors in the 1H --> 19F CP curve, showed a significant decrease with increasing temperature from 42 to 145 degrees C. This is due to the averaging of 1H-19F dipolar interactions originating from the molecular motion in the crystalline domain. The increase in molecular mobility in the crystalline domain was clearly shown by VT T1rho(F) and 1H --> 19F CP measurements in the phase transition temperature range.     

Conformational dynamics of bis(BF2)‐2,2′‐bidipyrrins revealed by through‐space 13C?19F and 19F?19F couplings

The conformation of [bis‐(N,N′‐difluoroboryl)]‐3,3′‐diethyl‐4,4′,8,8′,9,9′,10,10′‐octamethyl‐2,2′‐bidipyrrin (1) in solution was studied by analyzing the ¹³C? ¹⁹F and ¹⁹F? ¹⁹F through‐space spin–spin couplings. The ¹H and ¹³C NMR spectra were assigned on the basis of nuclear Overhauser effect spectroscopy (NOESY), heteronuclear single‐quantum correlation (HSQC), and heteronuclear multiple‐bond correlation (HMBC) experiments. The ¹⁹F spectrum of 1 was compared with that of 2‐ethyl‐1,3,5,6,7‐pentamethyl‐4,4‐difluoro‐4‐bor‐3a,4a‐diaza‐s‐indacen (2). The ¹⁹F? ¹⁹F through‐space spin? spin coupling in 1 was thus assigned and the coupling constant was obtained by simulating the coupling patterns. The obtained conformation of 1 was compared with those of the known complexes [bis‐(N,N′‐difluoroboryl)]‐3,3′,8,8′,9,9′‐hexaethyl‐4,4′,10,10′‐tetramethyl‐6,6′‐(4‐methylphenyl)‐2,2′‐bidipyrrin (3)and [bis‐(N,N′‐difluoroboryl)]‐9,9′‐diethyl‐4,4′,8,8′,10,10′‐hexamethyl‐3,3′‐bis(methoxycarbonylethyl)‐2,2′‐bidipyrrin (4). The conformational dynamics of 1, 3, and 4 was surveyed by observing the temperature dependence of the through‐space coupling constants between 253 and 333 K. The ¹³C? ¹⁹F and ¹⁹F? ¹⁹F through‐space spin–spin couplings thus confirm similar conformations of different BisBODIPYs in solution in contrast to earlier findings in the solid state. Copyright © 2009 John Wiley & Sons, Ltd.     

1H‐19F REDOR‐filtered NMR spin diffusion measurements of domain size in heterogeneous polymers

Solid state NMR spectroscopy is inherently sensitive to chemical structure and composition and thus makes an ideal method to probe the heterogeneity of multicomponent polymers. Specifically, NMR spin diffusion experiments can be used to extract reliable information about spatial domain sizes on multiple length scales, provided that magnetization selection of one domain can be achieved. In this paper, we demonstrate the preferential filtering of protons in fluorinated domains during NMR spin diffusion experiments using ¹H‐¹⁹F heteronuclear dipolar dephasing based on rotational echo double resonance (REDOR) MAS NMR techniques. Three pulse sequence variations are demonstrated based on the different nuclei detected: direct ¹H detection, plus both ¹H?¹³C cross polarization and ¹H?¹⁹F cross polarization detection schemes. This ¹H‐¹⁹F REDOR‐filtered spin diffusion method was used to measure fluorinated domain sizes for a complex polymer blend. The efficacy of the REDOR‐based spin filter does not rely on spin relaxation behavior or chemical shift differences and thus is applicable for performing NMR spin diffusion experiments in samples where traditional magnetization filters may prove unsuccessful. This REDOR‐filtered NMR spin diffusion method can also be extended to other samples where a heteronuclear spin pair exists that is unique to the domain of interest.     

Investigation of the correlations between 19F and 1H NMR signals for various mono‐ and di‐substituted octafluoro[2.2]paracyclophanes

A selection of mono‐ and pseudo ortho di‐substituted octafluoro[2.2]paracyclophane derivatives were analyzed using ¹⁹F‐¹H HOESY, ¹H COSY and ¹⁹F COSY techniques. This resulted in the unambiguous assignment of the ¹⁹F and ¹H NMR resonances, and also revealed interesting solvent effects and noteworthy coupling patterns for various J_HH, J_HF, and J_FF interactions, including observable through bond ⁷J_FF and ⁸J_FF couplings. For the four mono‐substituted derivatives, the assignments were achieved through the combination of ¹⁹F‐¹H HOESY, ¹H COSY and ¹⁹F COSY techniques. The C₂ symmetry of the six pseudo ortho di‐substituted derivatives that were examined produced simplified spectra, and careful inspection of the characteristic ¹H coupling patterns led to the assignment of ¹H signals. Therefore only ¹⁹F‐¹H HOESY experiments were required to complete the assignments for those molecules. Refinements and alternative strategies for previous protocols are presented for the molecules that were less responsive to nuclear Overhauser effect (nOe) experiments. Copyright © 2009 John Wiley & Sons, Ltd.     

1H,13C and 19F NMR data of N‐substituted 6‐(4‐methoxyphenyl)‐7H‐pyrrolo[2,3‐d]pyrimidin‐4‐amines in DMSO‐d6

Chemical shift assignment of seven N‐substituted 6‐(4‐methoxyphenyl)‐7H‐pyrrolo[2, 3‐d]pyrimidin‐4‐amines, six of which are fluorinated, have been performed based on ¹H, ¹³C, ¹⁹F, and 2D COSY, HMBC and HSQC experiments. Copyright © 2009 John Wiley & Sons, Ltd.     

Stacking Structure of Confined 1‐Butanol in SBA‐15 Investigated by Solid‐State NMR Spectroscopy

Understanding the complex thermodynamic behavior of confined amphiphilic molecules in biological or mesoporous hosts requires detailed knowledge of the stacking structures. Here, we present detailed solid‐state NMR spectroscopic investigations on 1‐butanol molecules confined in the hydrophilic mesoporous SBA‐15 host. A range of NMR spectroscopic measurements comprising of ¹H spin–lattice (T₁), spin–spin (T₂) relaxation, ¹³C cross‐polarization (CP), and ¹H,¹H two‐dimensional nuclear Overhauser enhancement spectroscopy (¹H,¹H 2D NOESY) with the magic angle spinning (MAS) technique as well as static wide‐line ²H NMR spectra have been used to investigate the dynamics and to observe the stacking structure of confined 1‐butanol in SBA‐15. The results suggest that not only the molecular reorientation but also the exchange motions of confined molecules of 1‐butanol are extremely restricted in the confined space of the SBA‐15 pores. The dynamics of the confined molecules of 1‐butanol imply that the ¹H,¹H 2D NOESY should be an appropriate technique to observe the stacking structure of confined amphiphilc molecules. This study is the first to observe that a significant part of confined 1‐butanol molecules are orientated as tilted bilayered structures on the surface of the host SBA‐15 pores in a time‐average state by solid‐state NMR spectroscopy with the ¹H,¹H 2D NOESY technique.     

Complete 1H, 13C, 19F and 31P NMR data assignment of CWC‐related chemicals N,N‐dialkyl‐P‐alkyl phosphonamidic fluorides

The complete multinuclear ¹H, ¹³C, ³¹P and ¹⁹F NMR data of symmetrically substituted amines containing N,N‐dialkyl‐P‐alkyl phosphonamidic fluorides are presented. Assignment was achieved, using various one‐and two‐dimensional NMR experiments. Copyright © 2010 John Wiley & Sons, Ltd.     

Variable temperature 19F solid‐state NMR study of the effect of electrostatic interactions on thermally‐stimulated molecular motions in perfluorosulfonate ionomers

This study uses variable temperature ¹⁹F solid‐state nuclear magnetic resonance (SSNMR) spectroscopy to determine the influence of electrostatic interactions on the T₁, T_1ρ, and T₂ values of Nafion®. Because of a “homogenizing” of the T₁'s as a result of spin diffusion, it was not possible to resolve from the T₁ experiments the relative motions of the side‐ and main‐chain. The initial increase in T_1ρ as a function of increasing temperature has been attributed to backbone rotations that increase with increasing temperature. The maxima observed in the T_1ρ plots suggest a change in the dominant relaxation mechanism at that temperature. The similarity in relaxation behavior of the side‐ and main‐chains suggests that the motions are dynamically coupled, because of the fact that the side‐chain is directly attached to the main‐chain. Two T_1ρ values were observed for the main‐chain at high temperatures, which has been attributed to a thermally activated ion‐hopping process. The results of T₂ studies show that correlated motions of the side‐ and main‐chain exist at low temperatures. However, at elevated temperatures the T₂ values for the side‐chain increase rapidly while remaining relatively constant for the main‐chain, indicating an onset of mobility of the side‐chains. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2177–2186, 2007     

Thermal characterization and solid‐state 13C‐NMR investigation of blends of poly(N‐phenyl‐2‐hydroxytrimethylene amine) and poly(N‐vinyl pyrrolidone)

The miscibility and thermal properties of poly(N‐phenyl‐2‐hydroxytrimethylene amine)/poly(N‐vinyl pyrrolidone) (PHA/PVP) blends were examined by using differential scanning calorimetry (DSC), high‐resolution solid‐state nuclear magnetic resonance (NMR) techniques, and thermogravimetric analysis (TGA). It was found that PHA is miscible with PVP, as shown by the existence of a single composition‐dependent glass transition temperature (T_g) in the whole composition range. The DSC results, together with the ¹³C crosspolarization (CP)/magic angle spinning (MAS)/high‐power dipolar decoupling (DD) spectra of the blends, revealed that there exist rather strong intermolecular interactions between PHA and PVP. The increase in hydrogen bonding and in T_g of the blends was found to broaden the line width of CH—OH carbon resonance of PHA. The measurement of the relaxation time showed that the PHA/PVP blends are homogeneous at least on the scale of 1–2 nm. The proton spin‐lattice relaxation in both the laboratory frame and the rotating frame were studied as a function of the blend composition, and it was found that blending did not appreciably affect the spectral densities of motion (sub‐T_g relaxation) in the mid‐MHz and mid‐KHz frequency ranges. Thermogravimetric analysis showed that PHA has rather good thermal stability, and the thermal stability of the blend can be further improved with increasing PVP content. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 237–245, 1999     

Parahydrogen‐Induced Polarization Transfer to 19F in Perfluorocarbons for 19F NMR Spectroscopy and MRI

Fluorinated substances are important in chemistry, industry, and the life sciences. In a new approach, parahydrogen‐induced polarization (PHIP) is applied to enhance ¹⁹F MR signals of (perfluoro‐n‐hexyl)ethene and (perfluoro‐n‐hexyl)ethane. Unexpectedly, the end‐standing CF₃ group exhibits the highest amount of polarization despite the negligible coupling to the added protons. To clarify this non‐intuitive distribution of polarization, signal enhancements in deuterated chloroform and acetone were compared and ¹⁹F–¹⁹F NOESY spectra, as well as ¹⁹F T₁ values were measured by NMR spectroscopy. By using the well separated and enhanced signal of the CF₃ group, first ¹⁹F MR images of hyperpolarized linear semifluorinated alkenes were recorded.     

Structural studies on aryl‐substituted enaminoketones and their thio analogues. Part I. Analysis of high‐resolution 1H, 13C NMR and 13C CP MAS spectra combined with GIAO‐DFT calculations

A series of aryl‐substituted enaminoketones and their thio analogues in CDCl₃ solution and in the solid state were studied by the use of high‐resolution ¹H and ¹³C as well as ¹³C cross polarization magic angle spinning (CP MAS) NMR spectra in combination with gauge including atomic orbitals‐density functional theory (GIAO‐DFT) calculations performed at the B3PW91/6–311 + + G(d,p) level of theory using the B3PW91/6‐311 + + G(d,p)‐optimized geometries. The analysis of the ¹³C NMR spectra in solution was done by using the Incredible Natural Abundance DoublE QUAntum Transfer Experiment (INADEQUATE) technique, whereas trends observed in the ¹³C shielding constants, calculated for the compounds studied, were a great help in assigning most of the signals in the ¹³C CP MAS NMR spectra. It was established on the basis of the experimental and theoretical NMR data that both groups of compounds exist in the form of Z‐s‐Z‐s‐E isomers in CDCl₃ solution as well as in the solid state, with the NH hydrogen atom involved in intramolecular hydrogen bonding. This conclusion is in agreement with the fact that some of the compounds studied reveal liquid‐crystalline properties. Three‐bond H, H and C, H coupling constants measured in solution played a crucial role in the structure elucidation. Copyright © 2009 John Wiley & Sons, Ltd.     

Interpreting 2hJ(F,N), 1hJ(H,N) and 1J(F,H) in the hydrogen‐bonded FH–collidine complex

Ab initio EOM‐CCSD calculations were performed to determine ¹⁹F,¹H, ¹⁹F,¹⁵N and ¹H,¹⁵N spin–spin coupling constants in model complexes FH–NH₃ and FH–pyridine as a function of the F—H and F—N distances. The absolute value of ¹J(F,H) decreases and that of ^1hJ(H,N) increases rapidly along the proton‐transfer coordinate, even in the region of the proton‐shared F—H—N hydrogen bond. In contrast, ^2hJ(F,N) remains essentially constant in this region. These results are consistent with the recently reported experimental NMR spectra of FH–collidine which show that ^1hJ(H,N) increases and ¹J(F,H) decreases, while ^2hJ(F,N) remains constant as the temperature of the solution decreases. They suggest that the FH–collidine complex is stabilized by a proton‐shared hydrogen bond over the range of experimental temperatures investigated, being on the traditional side of quasi‐symmetric at high temperatures, and on the ion‐pair side at low temperatures. Copyright © 2002 John Wiley & Sons, Ltd.     

19F Magic Angle Spinning Dynamic Nuclear Polarization Enhanced NMR Spectroscopy

The introduction of high‐frequency, high‐power microwave sources, tailored biradicals, and low‐temperature magic angle spinning (MAS) probes has led to a rapid development of hyperpolarization strategies for solids and frozen solutions, leading to large gains in NMR sensitivity. Here, we introduce a protocol for efficient hyperpolarization of ¹⁹F nuclei in MAS DNP enhanced NMR spectroscopy. We identified trifluoroethanol‐d₃ as a versatile glassy matrix and show that 12 mm AMUPol (with microcrystalline KBr) provides direct ¹⁹F DNP enhancements of over 100 at 9.4 T. We applied this protocol to obtain DNP‐enhanced ¹⁹F and ¹⁹F–¹³C cross‐polarization (CP) spectra for an active pharmaceutical ingredient and a fluorinated mesostructured hybrid material, using incipient wetness impregnation, with enhancements of approximately 25 and 10 in the bulk solid, respectively. This strategy is a general and straightforward method for obtaining enhanced ¹⁹F MAS spectra from fluorinated materials.     

Characterization of blends of poly(vinyl chloride) and poly(N‐vinyl pyrrolidone) by FTIR and 13C CP/MAS NMR spectroscopy

Blends of poly(vinyl chloride) (PVC) with Poly(N‐vinyl pyrrolidone) (PVP) were investigated by Fourier infrared spectroscopy (FTIR) and high‐resolution solid‐state ¹³C cross‐polarization/magic angle spinning (CP/MAS) nuclear magnetic resonance (NMR) spectroscopy. The intermolecular interactions between PVP and PVC are weaker than the self‐association of PVP and the inclusion of the miscible PVC results in the decreased self‐association of PVP chains, which was evidenced by the observation of high‐frequency shift of amide stretching vibration bands of PVP with inclusion of PVC. This result was further substantiated by the study of ¹³C CP/MAS spectra, in which the chemical shift of carbonyl resonance of PVP was observed to shift to a high field with inclusion of PVC, indicating that the magnetic shielding of the carbonyl carbon nucleus is increased. The proton spin‐lattice relaxation time in the laboratory frame (T₁ (H)) and the proton spin‐lattice relaxation time in the rotating frame (T_1ρ(H)) were measured as a function of the blend composition to give the information about phase structure. It is concluded that the PVC and PVP chains are intimately mixed on the scale of 20–30Å. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 2412–2419, 1999     

Characterization of the complex formation of 1,6‐anhydro‐β‐maltotriose with potassium using 1H and 39K NMR spectroscopy

The ¹H and ³⁹K longitudinal relaxation times (T₁) and ¹H diffusion coefficients were measured to investigate the complex formation of 1,6‐anhydro‐β‐maltotriose and potassium ions. Although the ¹H‐T₁ values of H3′, H5′, H1″ and H4″ decreased in the presence of potassium ions, ¹H chemical shifts and ¹H diffusion coefficients did not show significant changes. The long‐range coupling constants of ³J_C?H around the glycosyl bonds did not show significant changes either. In the measurements of ³⁹K spectra, the ³⁹K signal obviously broadened and the ³⁹K‐T₁ values decreased in the presence of 1,6‐anhydro‐β‐maltotriose, indicating the complex formation of 1,6‐anhydro‐β‐maltotriose and potassium ions. These results indicate that the conformation and molecular volume were unaffected in the complex formation. Copyright © 2009 John Wiley & Sons, Ltd.     

Enhancing NMR Sensitivity of Natural‐Abundance Low‐γ Nuclei by Ultrafast Magic‐Angle‐Spinning Solid‐State NMR Spectroscopy

Although magic‐angle‐spinning (MAS) solid‐state NMR spectroscopy has been able to provide piercing atomic‐level insights into the structure and dynamics of various solids, the poor sensitivity has limited its widespread application, especially when the sample amount is limited. Herein, we demonstrate the feasibility of acquiring high S/N ratio natural‐abundance ¹³C NMR spectrum of a small amount of sample (≈2.0 mg) by using multiple‐contact cross polarization (MCP) under ultrafast MAS. As shown by our data from pharmaceutical compounds, the signal enhancement achieved depends on the number of CP contacts employed within a single scan, which depends on the T_1ρ of protons. The use of MCP for fast 2D ¹H/¹³C heteronuclear correlation experiments is also demonstrated. The significant signal enhancement can be greatly beneficial for the atomic‐resolution characterization of many types of crystalline solids including polymorphic drugs and nanomaterials.     

One‐ and two‐dimensional NMR characterization of N‐vinyl‐2‐pyrrolidone/methyl acrylate copolymers

N‐vinyl‐2‐pyrrolidone/methyl acrylate (V/M) copolymers were prepared by free‐radical bulk polymerization using benzoyl peroxide as an initiator. The copolymer composition of these copolymers was calculated from ¹H NMR spectra. The radical reactivity ratios for N‐vinyl‐2‐pyrrolidone (V) and methyl acrylate (M) were r_V = 0.09, r_M = 0.44. These reactivity ratios for the copolymerization of V and M were determined using the Kelen–Tudos and nonlinear least‐squares error‐in‐variable methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers overlapped and were complex. The complete spectral assignment of the ¹³C and ¹H NMR spectra were done with distortionless enhancement by polarization transfer and two dimensional ¹³C‐¹H heteronuclear single quantum correlation spectroscopic experiments. The two‐dimensional ¹H‐¹H homonuclear total correlation spectroscopic NMR spectrum showed the various bond interactions, thus inferring the possible structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2225–2236, 2002     

One‐ and two‐dimensional NMR characterization of N‐vinyl‐2‐pyrrolidone/methyl acrylate copolymers

N‐vinyl‐2‐pyrrolidone/methyl acrylate (V/M) copolymers were prepared by free‐radical bulk polymerization using benzoyl peroxide as an initiator. The copolymer composition of these copolymers was calculated from ¹H NMR spectra. The radical reactivity ratios for N‐vinyl‐2‐pyrrolidone (V) and methyl acrylate (M) were r_V = 0.09, r_M = 0.44. These reactivity ratios for the copolymerization of V and M were determined using the Kelen–Tudos and nonlinear least‐squares error‐in‐variable methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers overlapped and were complex. The complete spectral assignment of the ¹³C and ¹H NMR spectra were done with distortionless enhancement by polarization transfer and two dimensional ¹³C‐¹H heteronuclear single quantum correlation spectroscopic experiments. The two‐dimensional ¹H‐¹H homonuclear total correlation spectroscopic NMR spectrum showed the various bond interactions, thus inferring the possible structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2225–2236, 2002     

19F Paramagnetic Relaxation Enhancement: A Valuable Tool for Distance Measurements in Proteins

Fluorine NMR paramagnetic relaxation enhancement was evaluated as a versatile approach for extracting distance information in selectively F‐labeled proteins. Proof of concept and initial applications are presented for the HIV‐inactivating lectin cyanovirin‐N. Single F atoms were introduced at the 4‐, 5‐, 6‐ or 7 positions of Trp49 and the 4‐position of Phe4, Phe54, and Phe80. The paramagnetic nitroxide spin label was attached to Cys residues that were placed into the protein at positions 50 or 52. ¹⁹F‐T₂ NMR spectra with different relaxation delays were recorded and the transverse ¹⁹F‐PRE rate, ¹⁹F‐Γ₂, was used to determine the average distance between the F nucleus and the paramagnetic center. Our data show that experimental ¹⁹F PRE‐based distances correspond to 0.93 of the ¹H_N‐PRE distances, in perfect agreement with the gyromagnetic γ¹⁹F/γ¹H ratio, thereby demonstrating that ¹⁹F PREs are excellent alternative parameters for quantitative distance measurements in selectively F‐labeled proteins.