Nonspherical large cages in structure I (sI) clathrates impose non-uniform motion of nonspherical guest molecules and anisotropic lineshapes in NMR spectra of the guest. In this work, we calculate the lineshape anisotropy of the linear CO2 molecule in large sI clathrate cages based on molecular dynamics simulations of this inclusion compound. The methodology is general and does not depend on the temperature and type of inclusion compound or guest species studied. The nonspherical shape of the sI clathrate hydrate large cages leads to preferential alignment of linear CO2 molecules in directions parallel to the two hexagonal faces of the cages. The angular distribution of the CO2 guests in terms of a polar angle θ and azimuth angle  and small amplitude vibrational motions in the large cage are characterized by molecular dynamics simulations at different temperatures in the stability range of the CO2 sI clathrate. These distributions are used to calculate the NMR powder spectrum of CO2 at different temperatures. The experimental 13C NMR lineshapes of CO2 guests in the large cages show a reversal of the skew between the low temperature (77 K) and the high temperature (238 K) limits of the stability of the clathrate. Good agreement between experimental lineshapes and calculated lineshapes is obtained. No assumptions regarding the nature of the guest motions in the cages are required.

<p>Nuclear magnetic resonance (NMR) spectroscopy is an established technique for macromolecular structure determination at atomic resolution. However, the majority of the current structure determination approaches require a large set of experiments and use large amount of data to elucidate the three dimensional protein structure. While current structure determination protocols may perform well in data-rich settings, protein structure determination still remains to be a difficult task in a sparse-data setting. Sparse data arises in high-throughput settings, for larger proteins, membrane proteins, and symmetric protein complexes; thereby requiring novel algorithms that can compute structures with provable guarantees on solution quality and running time.</p><p>In this dissertation project we made an effort to address the key computational bottlenecks in NMR structural biology. Specifically, we improved and extended the recently-developed techniques by our laboratory, and developed novel algorithms and computational tools that will enable protein structure determination from sparse NMR data. An underlying goal of our project was to minimize the number of NMR experiments, hence the amount of time and cost to perform them, and still be able to determine protein structures accurately from a limited set of experimental data. The algorithms developed in this dissertation use the global orientational restraints from residual dipolar coupling (RDC) and residual chemical shift anisotropy (RCSA) data from solution NMR, in addition to a sparse set of distance restraints from nuclear Overhauser effect (NOE) and paramagnetic relaxation enhancement (PRE) measurements. We have used tools from algebraic geometry to derive analytic expressions for the bond vector and peptide plane orientations, by exploiting the mathematical interplay between RDC- or RCSA-derived sphero-conics and protein kinematics, which in addition to improving our understanding of the geometry of the restraints from these experimental data, have been used by our algorithms to compute the protein structures provably accurately. Our algorithms, which determine protein backbone global fold from sparse NMR data, were used in the high-resolution structure determination protocol developed in our laboratory to solve the solution NMR structures of the FF Domain 2 of human transcription elongation factor CA150 (RNA polymerase II C-terminal domain interacting protein), which have been deposited into the Protein Data Bank. We have developed a novel, sparse data, RDC-based algorithm to compute ensembles of protein loop conformations in the presence of a moderate level of dynamics in the loop regions. All the algorithms developed in this dissertation have been tested on experimental NMR data. The promising results obtained by our algorithms suggest that our algorithms can be successfully applied to determine high-quality protein backbone structures from a limited amount of experimental NMR data, and hence will be useful in automated NOE assignments and high-resolution protein backbone structure determination from sparse NMR data. The algorithms and the software tools developed during this project are made available as free open-source to the scientific community.</p> / Dissertation

Abstract This thesis presents computational studies of both the static and dynamic parameters of the nuclear magnetic resonance (NMR) spectroscopy of gaseous xenon. First, state-of-the-art static magnetic resonance parameters are computed in small xenon clusters by using methods of quantum chemistry, and second, time-dependent relaxation phenomena are investigated via molecular dynamics simulations at different experimental conditions. Based on the underlying quantum and classical mechanics concepts, computational methods represent a procedure complementary to experiments for investigating the properties of atoms, molecules, clusters and solids. Static NMR spectral parameters, chemical shift, shielding anisotropy and asymmetry parameter, nuclear quadrupole coupling, and spin-rotation coupling, are calculated using different electronic structure methods ranging from the uncorrelated Hartree-Fock method to correlated second-order Møller-Plesset many-body perturbation, complete/restricted active space multiconfiguration self-consistent field, and to coupled-cluster approaches. The bond length dependence of these properties is investigated in the xenon dimer (Xe2). A well-characterized property in experimental NMR, the second virial coefficient of nuclear shielding, is theoretically calculated by a variety of methods and convincingly verified against experimental findings. Here, it is mandatory to include effects from special relativity as well as electron correlation. As a side result, a purely theoretical potential energy curve for Xe2, comparable to best experimental ones, is calculated. A pairwise additive scheme is established to approximate the NMR properties in differently coordinated sites of xenon clusters Xen (n = 2 - 12). Especially the pairwise additive chemical shift values are found to be in close agreement with quantum-chemical results and only a small scaling factor close to unity is needed for the correct behavior. Finally, a dynamical magnetic resonance property, the experimental nuclear spin-lattice relaxation rate R1 of monoatomic Xe gas due to the chemical shift anisotropy (CSA) mechanism is validated from first principles. This approach is based on molecular dynamics simulations over a large range of temperatures and densities, combined with the pairwise additive approximation for the shielding tensor. Therein, the shielding time correlation function is seen to reflect the characteristic time scales related to both interatomic collisions and cluster formation. For the first time, the physics of gaseous xenon is detailed in full in the context of CSA relaxation.

Various compounds were studied with solid-state 119Sn and 31P NMR spectroscopy and quantum chemical calculations. Connections were made between the shielding tensors and the geometric and electronic structures of the molecules. First, the 119Sn chemical shielding anisotropy of various para substituted tetraaryl tin compounds was shown to be dependent on the tilt angle of the phenyl rings. Tetrakis(o-tolyl) tin did not have the shielding anisotropy predicted by the tilt angle of the rings. It was suggested that ortho substitution distorts the structures of the phenyl rings causing the discrepancy. Analysis of the solid-state 31P NMR spectra of triphenylphosphorane ylides, Ph3P=CHC(O)R, determined that increasing the electron-donating effects of the R group decreased the δ33 component. Theoretical calculations showed that the component lay along the ylidic bond and was dependent on the difference in phosphorus-carbon bond lengths between the phenyl and ylidic bonds. Another study concerned the solid-state 31P NMR of the series of triphenylphosphine derivatives, PPh3-x(o-tolyl)x where x = 0 to 3. The addition of ortho methyl groups changed the position of the δ11 component which could be the result of the change in energy gap between the lone pair (HOMO) and σ* anti-bonding (LUMO). The solid-state 31P NMR spectra of deuterated piperazinium phosphonate and phosphonic acid were influenced by the shielding, dipolar and spin-spin interactions, as well as, second order quadrupolar effects. The spectrum of deuterated piperazinium phosphonate had a chemical shielding anisotropy of 130 ppm, an effective dipolar coupling of 2500 kHz and a one-bond phosphorus-deuterium J coupling of 90 Hz. The phosphorus-deuterium bond length was predicted to be 1.44(2) Å. A deuterium quadrupolar coupling constant of 104 kHz was obtained from the CP/MAS 2H spectrum. The non-axial symmetry of phosphonic acid complicated the analysis of the 31P spectrum. Phosphorus-deuterium bond lengths of 1.44(5) Å and 1.40(4) Å were obtained for the two inequivalent sites in the unit cell.

Abstract The present thesis describes a method for characterization of liquid crystals in confined spaces by means of NMR of probe atoms and molecules. 129Xe isotope enriched xenon gas and 13C isotope enriched methyl iodide and methane were used as probes. Behavior of solutes and liquid crystals confined to porous materials was investigated using 129Xe and 13C NMR spectroscopy. Uniaxial nematic liquid crystals Phase 4 and ZLI 1115 were used as a medium. Controlled pore glass with well defined and known properties was used as a porous material. The behavior of liquid crystals and solutes in various different size pores, temperatures and magnetic fields at different solute concentrations was explained. The average pore diameter of the material varied from mesopores to macropores. The studied temperature range covered solid, nematic and isotropic phases of bulk liquid crystals, and the highest magnetic field was 2.5 times stronger than the lowest one used (4.70 T). The chemical shifts, intensities, and line shapes of the resonance signals from the solutes were observed to contain lots of information about the effect of confinement on the state of the liquid crystals. Especially the line shape of the 13C resonances of methyl iodide was observed to be very sensitive to the liquid crystal orientation distribution in the pores. By varying experimental conditions the relative contribution of field and the surface forces of pore walls to the orientation of liquid crystal molecules inside the pores was seen to change quite drastically. In addition, it was also observed that when the sample is cooled very rapidly, xenon atoms do not squeeze out from the freezing medium but they are occluded inside the solid lattice, and their chemical shift is very sensitive to crystal structure. Furthermore, because solutes experienced on average isotropic environment inside the smallest pores, isotropic value of the shielding tensor could be determined at exactly the same condition and temperature as anisotropic counterpart between the pore particles. Thus, for the first time in the solution state, shielding anisotropies could be determined as a function of temperature.

Ce mémoire présente une méthodologie théorique pour comprendre l'origine de différence de comportement dynamique de complexes alkylidènes, catalyseurs de type Schrock de la métathèse des oléfines, greffés un support de silice amorphe. Dans un travail antérieur, les différences entre les valeurs de l'anisotropie de déplacement chimique (CSA) obtenus par des mesures de RMN du solide et celles estimées par le calcul pour des systèmes figés avaient conduit à suggérer des régimes dynamiques différents pour ces complexes, certains étant proposés comme immobiles, d'autres comme mobiles. Dans le premier groupe se trouve les complexes du molybdène et dans le second les complexes du tungstène, rhénium et tantale. Dans le cadre de cette thèse, nous nous sommes donc attachés à mettre en place une méthodologie pour déterminer ces CSA et donc la nature de la dynamique de chaque système qui conduit au CSA moyenné. Nous nous sommes d'abord intéressés à des systèmes moléculaires pour révéler des interactions non covalentes entre les complexes et le support silice à partir d'une approche de type petit cluster en utilisant divers niveaux de calculs DFT et modèles moléculaires. Cette modélisation moléculaire de la silice étant insuffisante, nous avons entrepris une modélisation de la surface de silice amorphe par dynamique moléculaire classique dont les caractéristiques ont été comparées aux données expérimentales existantes. Le comportement dynamique de ces systèmes greffés sur silice amorphe a été simulé par dynamique moléculaire ab initio QM/MM, couplant une description quantique du complexe organométallique à une description classique du support. Ces études dynamiques ont conduit à des valeurs de CSA moyennées dans le temps de la dynamique. La comparaison de ces valeurs calculées et des valeurs expérimentales a permis d'apporter des éléments de réponse sur l'origine des différences de comportement dynamique de ces complexes alkylidènes. De façon remarquable des mouvements d'ensemble des espèces greffées par rapport à la surface de silice et des modifications de la coordination du métal par l'apparition d'interaction agostique contribuent à moyenner le CSA. / This work presents a theoretical study aimed at analyzing the origin of the differences in the dynamics of alkylidenes complexes, known as Schrock olefin metathesis catalysts, supported on amorphous silica. The difference between the experimental chemical shift anisotropies (CSA) obtained from solid state NMR measurements and the values computed for the most stable configurations have been used in previous work to suggest different dynamical behaviors for the supported complexes. Some of the complexes were suggested to have limited mobilities while others were suggested to be mobiles. In the first group, one finds Mo complexes, and in the second, W, Re and Ta complexes. In this thesis, a methodology was established to compute the CSA and to obtain information on the dynamics that average the CSA over time. In the first part of this work, molecular species were considered and the non covalent interactions between the surface and the grafted complexes were studied with various DFT levels of calculations and various molecular models. This molecular modeling being inappropriate, a better representation of the surface of amorphous silica was carried out with classical molecular dynamic methods. The nature of the surface was analyzed and compared with available experimental information. In a following step, the dynamic behavior of these complexes was determined using anab initio molecular dynamics (QM/MM) approach in which the metal fragments are treated at the quantum level and the support represented in a classical manner. These molecular dynamics studies yield time averaged CSA that are reasonably close to the experimental values and confirm in particular the partition into immobile (Mo) and mobile (W, Re, Ta) complexes. A detailed analysis of the results leads to a better understanding of the nature of the dynamics. Remarkably, motions relative to the silica surface and vibrations influencing the coordination sphere of the metal involving in particular agostic interactions both contribute to average the CSA.

No description available.

The work presented in this thesis has two parts. The first part deals with methodological developments in the area of solid-state NMR, relevant to the study of partially ordered systems. Liquid crystals are best examples of such partially ordered systems and they are easily oriented by the magnetic field used for the NMR study. They provide spectra rich in information useful for the study of structure and dynamic s of the oriented molecule. Dipolar couplings and anisotropic chemical shifts are relatively easy to obtain for these systems. However, the methodologies used for extracting the required information are constantly undergoing change, with newer ideas being used for optimal use of the technique and increasing the sensitivity of the methodology. In this thesis, existing methods used for obtaining dipolar couplings from oriented liquid crystalline samples are examined in detail and conditions for optimal use of the methods are investigated. Different approaches for enhancing the sensitivity of the techniques are also proposed. Estimation of chemical shift anisotropy of carbons for a molecule that is used as a building block for several mesogens has been obtained and its utility for estimating the order parameters of the system have been examined. The second part of the thesis deals with the application of solid state NMR methods to the study of a number of novel liquid crystalline systems and for the estimation of dynamics, order and orientation of the mesogenic molecules in the magnetic field. Chapter-2 deals with a detailed and systematic study to improve the sensitivity of cross-polarization based separated local field (SLF) NMR spectroscopy techniques such as PISEMA(Polarization Inversion Spin Exchange at the Magic Angle) and PDLF(Pro-ton Detected Local Field). The chapter has been further divided into three sections. Section-A describes the optimization procedure for cross-polarization period for reducing zero-frequency peaks in SLF experiments. Polarization Inversion(PI) is one of the important components of PISEMA and plays a crucial role in enhancing the dipolar cross-peaks and suppressing the axial-peaks. Shortening this period has the advantage of less r.f. power input into the system, thus less susceptibility to sample heating. Therefore it is crucial to arrive at the optimum condition for which maximum sensitivity and resolution are obtained. A detailed experimental investigation of the role of the initial po1arization period has been carried out for two different samples of static oriented liquid crystalline material at two different temperatures and a contact time of 2ms has been found to be optimal for such samples. Insection-B of this chapter, the initial preparation period of the experiment is considered as a possible means of increasing the sensitivity of the experiment. Thus the use of cross-polarization via the dipolar bath by the use of a diabatic demagnetization in the rotating frame(ADRF-CP) has been proposed to be incorporated into PISEMA. To understand the CP dynamics, magnetization in double-and zero-quantum reservoirs of an ensemble of spin-1/2 nuclei and their role in determining the sensitivity the experiments have been theoretically examined. Experimentally, a modification incorporating ADRF-CP is shown to result in enhancement of signal-to-noise by as much as 90% in the case of rigid single crystals of a model peptide and up to 50% in non-rigid, partially ordered liquid crystalline systems. In section-C another useful SLF technique known as PDLF spectroscopy has also been examined. In this case a sweep of one of the r.f. amplitudes(RAMP-CP),rather than ADRF is found to work well. The reason for the different behaviours has been discussed. Chapter-3 highlights two experimental approaches used to extract the chemical shift anisotropy(CSA) tensor information from rotating solids. Section-A is devoted to the measurement of the CSA values of thiophene by using MAS side band analysis, by extracting the principal values from the intensities of just a few spinning side bands. Experiments have been performed on thiophene-2 carboxylic acid and thiophene-3 carboxylic acid samples and the carbon CSA values have been obtained. In section-B, CSA values of carbons of the core unit of the liquid crystal4- hexyloxybenzoic acid (HBA) have been obtained by using the recoupling pulse sequence SUPER(Separation of Undistorted Powder patterns by Effortless Recoupling).HBA belongs to an important class of thermotropic liquid crystals which are structurally simple and often used as starting materials for many novel mesogens. As this molecule could serve as an ideal model compound, high resolution13C NMR studies of HBA in solution, solid and liquid crystalline phases have been also undertaken. The CSA values obtained from the 2D SUPER experiment showed good agreement to those computed by DFT calculations. The CSA values were used for obtaining the order parameter of the system at different temperatures. These matched well the order parameter obtained from the 13C-1 H dipolar couplings in the nematic phase determined by SLF spectroscopy at various temperatures. A knowledge of the CSA of the carbons is thus very useful, as they can be used for gaining knowledge about the system from the chemical shifts obtained from a simple 1D spectrum. In chapter-4, 1-and 2-dimensional13CNMR techniques have been utilized to obtain extensive information about some novel mesogenic molecules. Four molecules of different structure and topology have been taken up for study. These molecules have the following features. Mesogen-1 has a terminal hydroxyl group. Such systems with further modification can result in mesogenic monomers for side chain liquid crystalline polymers. Mesogen-2 has a dimethyl amino group at one end and has three phenyl groups connected by appropriate linking units that form the core. In the third case, mesogen-3, the terminal hydroxyl group of mesogen-1 is replaced with a hydrogen such that13C-1 H dipolar couplings provide directly information on molecular ordering and orientation. In the fourth case, mesogen-4, the core is built with four phenyl rings. Here the fourth ring is linked to other three rings via a flexible chain unit. In each of these cases the 2DSLFNMR experiments have been carried out where13C-1 H dipolar couplings as well as13C chemical shifts were used for obtaining the order parameters of various segments of the molecule. The data provide useful insight into the phase behaviour, ordering and orientation of the molecules. Chapter-5 discusses the applications of the natural abundance 13CNMR techniques to thiophene based mesogens, that have the potential for use in molecular electronics material. Typically, these molecules consist of phenyl rings appropriately connected by linking units with thiophene. Different core units as well as different linking units to thiophene have been considered. The six mesogens thus obtained have been investigated in detail using 1D and 2D NMR methods.13C-1 H dipolar couplings have been used to obtain ordering information, that show interesting correlation to the molecular orientation and dynamics.