Advanced magnetic resonance strategies for the elucidation of nanostructured soft matter.

An overview is given on advanced magnetic resonance strategies and techniques, both nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR), as applied to nanostructured soft matter. In addition, the combination of the two forms of spectroscopy to enhance signal intensity in NMR by means of dynamic nuclear polarization (DNP) is described. It is shown how these techniques can provide unique information on the structure of soft matter as well as the local dynamics of the constituents. Examples of recent applications are described, including dendronized and thermoresponsive polymers, hydrogels, synthetic and bio-inspired polymers, as well as polypeptides and biopolymers.

Hyperpolarized 1H long lived states originating from parahydrogen accessed by rf irradiation.

Hyperpolarization has found many applications in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, its usage is still limited to the observation of relatively fast processes because of its short lifetimes. This issue can be circumvented by storing the hyperpolarization in a slowly relaxing singlet state. Symmetrical molecules hyperpolarized by Parahydrogen Induced Hyperpolarization (PHIP) provide straightforward access to hyperpolarized singlet states because the initial parahydrogen singlet state is preserved at almost any magnetic field strength. In these systems, which show a remarkably long (1)H singlet state lifetime of several minutes, the conversion of the NMR silent singlet state to observable magnetization is feasible due to the existence of singlet-triplet level anti-crossings. Here, we demonstrate that scaling the chemical shift Hamiltonian by rf irradiation is sufficient to transform the singlet into an observable triplet state. Moreover, because the application of one long rf pulse is only partially converting the singlet state, we developed a multiconversion sequence consisting of a train of long rf pulses resulting in successive singlet to triplet conversions. This sequence is used to measure the singlet state relaxation time in a simple way at two different magnetic fields. We show that this approach is valid for almost any magnetic field strength and can be performed even in the less homogeneous field of an MRI scanner, allowing for new applications of hyperpolarized NMR and MRI.

High resolution para-hydrogen induced polarization in inhomogeneous magnetic fields.

The application of parahydrogen for the generation of hyperpolarization has increased continuously during the last years. When the chemical reaction is carried out at the same field as the NMR experiment (PASADENA protocol) an antiphase signal is obtained, with a separation of the resonance lines of a few Hz. This imposes a stringent limit to the homogeneity of the magnetic field in order to avoid signal cancellation. In this work we detect the signal arising from hyperpolarized Hexene by means of a CPMG pulse train. After Fourier transformation the obtained J-spectra not only presents an enhanced spectral resolution but also avoids partial peak cancellation.

Level anti-crossings in ParaHydrogen Induced Polarization experiments with Cs-symmetric molecules.

Hyperpolarization by means of ParaHydrogen Induced Polarization (PHIP) has found increasing applications since its discovery. However, in the last decade only a few experiments have been reported describing the hydrogenation of symmetric molecules. A general AA'BB' system is studied here. Calculations of the spin dynamics with the density matrix formalism support the experimental findings, providing profound understanding of the experiments in Cs-symmetric molecules. Level anti-crossings between states related to the triplet and the singlet state of one pair of the protons are identified as being responsible for hyperpolarization transfer in a PHIP experiment, when the former p-H(2) protons occupy the sites AA'. The hydrogenation of acetylene dicarboxylic acid dimethylester with parahydrogen is used to illustrate the case. The theoretical treatment applied to this particular reaction explains the signal enhancements in both groups of protons in the spectrum when the sample is placed in the proper magnetic field strength, including the phase inversion of the signal of the methyl group. The treatment described here can be extended to every molecule which can be approximated as an AA'BB' system.

Multinuclear solid state NMR investigation of two polymorphic forms of ciprofloxacin-saccharinate.

Two polymorphic forms of a novel pharmaceutical compound, ciprofloxacin-saccharinate (CIP-SAC), are analyzed using one dimensional (1D) and two dimensional (2D) (1)H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally (15)N spectroscopy and (1)H-(13)C correlation experiments were performed to complement our conclusions. The 1D (1)H NMR spectra of CIP and complexes reveal valuable information about the ionic bonding between ciprofloxacin and saccharine. Additionally, these spectra allow us to perform a clear characterization of each solid form, giving the number of molecules per unit cell in one of the polymorphs. From 2D (1)H-(1)H spectra obtained through double quantum correlations we can arrive at important conclusions about the hydrogen bonding, conformation, and intra and inter-molecular interactions present in these compounds. Comparing and contrasting the (1)H-(1)H correlation data obtained for both polymorphic forms and taking into account the single crystal structure data existing for the solid form CIP-SAC (II) was possible to extract some conclusions on the polymorph CIP-SAC (I) where no single crystal information is available. (1)H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.

Fast and slow dynamics in a discotic liquid crystal with regions of columnar order and disorder.

Aromatic disk-shaped molecules tend to self-organize into a herringbone packing where the disks are inclined at angles ±Î¸ with respect to the axis of the column. In discotic liquid crystals this can introduce defects between stacks of limited length. In a C(3)-symmetric hexa-peri-hexabenzocoronene, solid-state NMR, x-ray scattering, and rheology identifies such a packing with θ=43° and stacks of about seven disks. Disordered regions containing defects fill the space in between the ordered stacks. Biaxial intra- and intercolumnar dynamics differing by eight decades are identified.

Magnetic resonance imaging of dissolved hyperpolarized 129Xe using a membrane-based continuous flow system.

A technique for continuous production of solutions containing hyperpolarized (129)Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized (129)Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of (129)Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized (129)Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.

Resolution enhancement in MRI of laser polarized 3He by control of diffusion.

Diffusion of atoms or molecules in presence of magnetic field gradients not only attenuates the NMR signal but also leads to distortions close to restricting boundaries. This phenomenon is most evident in imaging with laser polarized (LP) noble gases. Diffusion of gases can be manipulated, however, by admixing inert gases of different molecular weight. In this work we analyze the effect of mixing LP-(3)He with SF(6) on the image quality of a phantom consisting of an arrangement of capillaries with different diameters. Admixing buffer gases of higher molecular weight changes the contrast and offers a means to record images with high spatial and time resolution. Additionally we demonstrate how distortions due to edge enhancement can be reduced even for long timed MRI-sequences.

Relaxation-based distance measurements between a nitroxide and a lanthanide spin label.

Distance measurements by electron paramagnetic resonance techniques between labels attached to biomacromolecules provide structural information on systems that cannot be crystallized or are too large to be characterized by NMR methods. However, existing techniques are limited in their distance range and sensitivity. It is anticipated by theoretical considerations that these limits could be extended by measuring the enhancement of longitudinal relaxation of a nitroxide label due to a lanthanide complex label at cryogenic temperatures. The relaxivity of the dysprosium complex with the macrocyclic ligand DOTA can be determined without direct measurements of longitudinal relaxation rates of the lanthanide and without recourse to model compounds with well defined distance by analyzing the dependence of relaxation enhancement on either temperature or concentration in homogeneous glassy frozen solutions. Relaxivities determined by the two calibration techniques are in satisfying agreement with each other. Error sources for both techniques are examined. A distance of about 2.7 nm is measured in a model compound of the type nitroxide-spacer-lanthanide complex and is found in good agreement with the distance in a modeled structure. Theoretical considerations suggest that an increase of the upper distance limit requires measurements at lower fields and temperatures.

Effect of chain topology on the self-organization and dynamics of block copolypeptides: from diblock copolymers to stars.

The effect of chain topology on (i) the peptide secondary structure, (ii) the nanophase self-assembly, and (iii) the local segmental and global peptide relaxations has been studied in a series of model diblock and 3-arm star copolypeptides of poly(epsilon-carbobenzyloxy-L-lysine) (PZLL) and poly(gamma-benzyl-L-glutamate) (PBLG) with PZLL forming the core. Diblock copolypeptides are nanophase separated with PBLG and PZLL domains comprising alpha-helices packed in a hexagonal lattice. Star copolypeptides are only weakly phase separated, comprising PBLG and PZLL alpha-helices in a pseudohexagonal lattice. Phase mixing has profound consequences on the local and global dynamics. The relaxation of the peptide secondary structure speeds up, and the helix persistence length is further reduced in the stars, signifying an increased concentration of helical defects.

Origin of the complex molecular dynamics in functionalized discotic liquid crystals.

The molecular dynamics of three dipole functionalized hexa-peri-hexabenzocoronenes have been studied using site-specific NMR techniques and dielectric spectroscopy as a function of temperature and pressure. These probes (i) suggest that the thermodynamic state completely controls the dynamic response, (ii) clarify the origin of two dynamic processes associated with the presence of two glass temperatures, and (iii) provide the first phase diagram for substances of this kind.

Diffusion and conformation of peptide-functionalized polyphenylene dendrimers studied by fluorescence correlation and 13C NMR spectroscopy.

We report on the combined use of fluorescence correlation spectroscopy (FCS) and 1H and 13C NMR spectroscopy to detect the size and type of peptide secondary structures in a series of poly-Z-L-lysine functionalized polyphenylene dendrimers bearing the fluorescent perylenediimide core in solution. In dilute solution, the size of the molecule as detected from FCS and 1H NMR diffusion measurements matches nicely. We show that FCS is a sensitive probe of the core size as well as of the change in the peptide secondary structure. However, FCS is less sensitive to functionality. A change in the peptide secondary conformation from beta-sheets to alpha-helices detected by 13C NMR spectroscopy gives rise to a steep increase in the hydrodynamic radii for number of residues n > or = 16. Nevertheless, helices are objects of low persistence.

Intermediate temperature proton conductors for PEM fuel cells based on phosphonic acid as protogenic group: a progress report.

The melting behaviour and transport properties of straight chain alkanes mono- and difunctionalized with phosphonic acid groups have been investigated as a function of their length. The increase of melting temperature and decrease of proton conductivity with increasing chain length is suggested to be the consequence of an increasing ordering of the alkane segments which constrains the free aggregation of the phosphonic acid groups. However, the proton mobility is reduced to a greater extent than the proton diffusion coefficient indicating an increasing cooperativity of proton transport with increasing length of the alkane segment. The results clearly indicate that the "spacer concept", which had been proven successful in the optimization of the proton conductivity of heterocycle based systems, fails in the case of phosphonic acid functionalized polymers. Instead, a very high concentration of phosphonic acid functional groups forming "bulky" hydrogen bonded aggregates is suggested to be essential for obtaining very high proton conductivity. Aggregation is also suggested to reduce condensation reactions generally observed in phosphonic acid containing systems. On the basis of this understanding, the proton conductivities of poly(vinyl phosphonic acid) and poly(meta-phenylene phosphonic acid) are discussed. Though both polymers exhibit a substantial concentration of phosphonic acid groups, aggregation seems to be constrained to such an extent that intrinsic proton conductivity is limited to values below sigma = 10(-3) S cm(-1) at T = 150 degrees C. The results suggest that different immobilization concepts have to be developed in order to minimize the conductivity reduction compared to the very high intrinsic proton conductivity of neat phosphonic acid under quasi dry conditions. In the presence of high water activities, however, (as usually present in PEM fuel cells) the very high ion exchange capacities (IEC) possible for phosphonic acid functionalized ionomers (IEC >10 meq g(-1)) may allow for high proton conductivities in the intermediate temperature range (T approximately 120 -160 degrees C).

Morphological differences in semicrystalline polymers: Implications for local dynamics and chain diffusion.

Morphological differences in semicrystalline polymers due to different crystallization conditions have implications for the chain motion. The local dynamics in the noncrystalline regions of solution-crystallized linear polyethylene is lower than in a melt-crystallized sample, but the opposite is observed for chain diffusion between noncrystalline and crystalline regions. The activation enthalpy for chain diffusion, however, is the same, indicating that entropic differences in the noncrystalline regions strongly influence the chain diffusion of the same polymer in different morphologies.

Bulk chemical shifts in hydrogen-bonded systems from first-principles calculations and solid-state-NMR.

We present an analysis of bulk (1)H NMR chemical shifts for a series of biochemically relevant molecular crystals in analogy to the well-known solvent NMR chemical shifts. The term bulk shifts denotes the change in NMR frequency of a gas-phase molecule when it undergoes crystallization. We compute NMR parameters from first-principles electronic structure calculations under full periodic boundary conditions and for isolated molecules and compare them to the corresponding experimental fast magic-angle spinning solid-state NMR spectra. The agreement between computed and experimental lines is generally very good. The main phenomena responsible for bulk shifts are packing effects (hydrogen bonding and pi-stacking) in the condensed phase. By using these NMR bulk shifts in well-ordered crystalline model systems composed of biologically relevant molecules, we can understand the individual spectroscopic signatures of packing effects. These local structural driving forces, hydrogen bonding, pi-stacking, and related phenomena, stand as a model for the forces that govern the assembly of much more complex supramolecular aggregates. We show to which accuracy condensed-phase ab initio calculations can predict structure and structure-property relationships for noncovalent interactions in complex supramolecular systems.

Diffusion in binary gas mixtures studied by NMR of hyperpolarized gases and molecular dynamics simulations.

The dependence of the individual mean square displacement of rare gases in binary mixtures is studied by a combined experimental and theoretical approach. We show that the diffusion constant can be varied in a considerable range by changing the molar fractions of the mixtures. On the experimental side, NMR diffusion measurements are done on hyperpolarized 3He and 129Xe, mixed with several inert buffer gases, in the presence of a magnetic field gradient. The results are compared to diffusion coefficients obtained from atomistic molecular dynamics simulations based on Lennard-Jones type potentials of the corresponding gas mixtures, and to appropriate analytical expressions, yielding very good mutual agreement. This study is the first quantitative validation of the effects of the mutual interactions between gas particles on the individual diffusion properties. It is shown that the dependency of gas phase diffusion properties on the local chemical environment may not be neglected, e.g. in diffusion-controlled chemical reactions.

Orientation dynamics in isotropic phases of model oligofluorenes: glass or liquid crystal.

Orientation molecular dynamics were investigated in a series of "defect-free" oligofluorenes by depolarized dynamic light scattering and dynamic NMR spectroscopy. Typical liquid crystalline pretransitional dynamics were observed upon cooling the isotropic phase to the liquid crystalline phase with strong increase of the scattered intensity and slowing down of the characteristic time of the probed collective relaxation. This is well accounted for by the Landau-de Gennes theory, however, with a strong temperature dependence of the viscosity coefficient, reflecting the proximity of the glass transition. For the trimer the two transitions almost overlap and the molecular orientation coincide with the alpha-relaxation associated with the glass transition. The NMR measurements confirm that the time scale of the dynamics is completely governed by the glass process, yet the geometry of the motion is anisotropic, yielding order parameters ranging from 0.15 to 0.25 for the long axis in the liquid crystalline phase. The glass transition is therefore geometrically restricted with poorly ordered mesophase which is consistent with the weak transverse phonons in the light scattering experiment down to Tg+20 K.

A site-directed spin-labeling study of surfactants in polymer-clay nanocomposites.

Polymer-clay nanocomposites exhibit much improved mechanical, physical, and chemical properties compared to the pure polymer. The interaction of polymer and organically modified silicates is mainly influenced by the surfactant layer in the system. To investigate the structure and dynamics of this surfactant layer, various electron paramagnetic spectroscopy (EPR) techniques were applied. Continuous wave EPR experiments showed a temperature-dependent heterogeneous mobility of the surfactant layer in organoclay as well as a difference in dynamics along the alkyl chain. Intercalation of polystyrene causes a significant slowdown in surfactant dynamics. Electron spin echo envelope modulation indicates a closer contact of the polymer with the mid of the surfactant tail than with the end of the tail. From the obtained data the picture of flatly lying surfactants on clay platelets with a mobility gradient along their alkyl chains can be drawn.

Structure of amorphous poly-(ethylmethacrylate): a wide-angle x-ray scattering study.

The local, temperature dependent structure of poly-(ethylmethacrylate) was studied with wide-angle x-ray scattering. The results were set into context to recent wide-angle neutron scattering results as well as to the results from a multitude of studies of the dynamics of this polymer. The temperature dependence of the wide angle x-ray results point to the development of local order which is backed by the neutron scattering results and which is connected to characteristic temperatures of the relaxation dynamic T(g) and T(c). The poly-(ethylmethacrylate) was studied in its predominantly syndiotactic as well as predominantly isotactic state displaying vastly different local structures as manifested in the x-ray results.