| 1. |
|
|
| 2. |
- Ghalebani, Leila
(author)
-
Probing Dynamics of Oligosaccharides by Interference Phenomena in NMR Relaxation
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information that is difficult to be determined by other means. Moreover, the anisotropy of the carbon-13 chemical shielding tensor in the methylene group has been estimated, using the interference between dipole-dipole and chemical shift anisotropy.This thesis also discusses using the PRE to investigate sugar dynamics relative to a paramagnetic MRI contrast agent in solution, which might be important in medicine. We have studied the intramolecu-lar dynamics of the trisaccharide raffinose in the presence of a gadolinium complex. We also investigated the effect of translational diffusion instead of rotational diffusion, which is normally more important in NMR. The paramagnetically enhanced spin–lattice relaxation rates of aqueous protons over a wide range of magnetic fields and of carbon-13 and protons of the sugar at high fields have been measured. The nuclear magnetic relaxation dispersion of water protons and the PREs of proton and carbon in the sugar are interpreted in terms of the model recently developed in our laboratory, allowing both outer- and inner-sphere PREs for water protons, but allowing only the outer sphere PRE for nuclei in the sugar. We found that the relative diffusion has a stronger effect on the PRE than the electron spin relaxation.
|
|
| 3. |
- Khan, Shehryar, 1986-
(author)
-
Combined Quantum Mechanical and Molecular Dynamics study of paramagnetic complexes : Towards an understanding of electronic spin relaxation
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- The prime objectives of contrast agents in Magnetic Resonance Imaging (MRI) is to accelerate the relaxation rate of the solvent water protons in the surrounding tissue. Paramagnetic relaxation originates from dipole-dipole interactions between the nuclear spins and the fluctuating magnetic field induced by unpaired electrons. Currently Gadolinium(III) chelates are the most widely used contrast agents in MRI, and therefore it is incumbent to extend the fundamental theoretical understanding of parameters that drive the relaxation mechanism in these complexes. In compounds such as Gadolinium(III) complexes with total electron spins higher than 1 (in this case S=7/2) the Zero-Field Splitting (ZFS) plays a significant role in influencing the electron spin dynamics and nuclear spin dynamics. For this purpose, the current research delves into an understanding of the relaxation process, focusing on ZFS in various complexes of interest, using multi-scale modelling by combining quantum, semi-quantum and newtonian methods.We compare and contrast Density Function Theory (DFT) with multi-configurational quantum chemical calculation and find that DFT is highly functional dependent and unreliable in accurately reproducing experimental data for the static ZFS. It was found that long-range corrected functionals (in particular LC-BLYP) perform significantly better as compared to other functionals in predicting the magnitude of the static ZFS. We study hydrated Gd(III) and Eu(II) systems to compare and contrast these isoelectronic complexes (both contain 7 unpaired electrons in their valence shell) and through ab-initio molecular dynamics (AIMD) sampling followed by multi-reference quantum chemical calculations, it was established that inclusion of the first shell has a dominant influence (over 90%) on the ZFS. We also studied the complex [Gd(III)(HPDO3A)(H2O)], which is of clinical relevance as a contrast agent for MRI, through post-Hartree-Fock and DFT calculations by utilizing configurations derived from AIMD trajectories. From the fluctuations in the ZFS tensor, we extract a correlation time of the transient ZFS which is on the sub-picosecond time scale, showing a faster decay than experimental data.
|
|
| 4. |
- Nikkhou Aski, Sahar, 1976-
(author)
-
NMR Studies of Inclusion Compounds
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- This thesis presents the application of some of the NMR methods in studying host-guest complexes, mainly in solution. The general focus of the work is on investigating the reorientational dynamics of some small molecules that are bound inside cavities of larger moieties. In the current work, these moieties belong to two groups: cryptophanes and cyclodextrins. Depending on the structure of the cavities, properties of the guest molecules and the formed complexes vary. Chloroform and dichloromethane are in slow exchange between the cage-like cavity of the cryptophanes and the solvent, on the chemical shift time scale, whereas adamantanecarboxylic acid, quinuclidine and 1,7-heptanediol in complex with cyclodextrins are examples of fast exchange. Kinetics and thermodynamics of complexation are studied by measuring exchange rates and translational self-diffusion coefficients by means of 1-dimenssional exchange spectroscopy and pulsed-field gradient (PFG) NMR methods, respectively. The association constants, calculated using the above information give estimates of the thermodynamic stability of the complexes. Carbon-13 spin relaxation data were obtained using conventional relaxation experiments, such as inversion recovery and dynamic NOE, and in some cases HSQC-type (Hetereonuclear Single Quantum Correlation Spectroscopy) experiments. Motional parameters for the free and bound guest, and the host molecules were extracted using different motional models, such as Lipari-Szabo, axially symmetric rigid body, and Clore models. Comparing the overall correlation times and the order parameters of the free and bound guest with the overall correlation time of the host molecule one can estimate the degree of the motional restriction, brought by the complexation, and the coupling between the motion of the bound guest and the reorientation of the host molecule. In one case, the guest motions were also investigated inside the cavities of a solid host material.
|
|
| 5. |
- Šoltésová, Mária, 1984-
(author)
-
Fast Dynamic Processes in Solution Studied by NMR Spectroscopy
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- Nuclear magnetic resonance (NMR) spectroscopy is capable to deliver a detailed information about the dynamics on molecular level in a wide range of time scales, especially if accompanied by suitably chosen theoretical tools. In this work, we employed a set of high-resolution NMR techniques to investigate dynamics processes in several weakly interacting molecular systems in solution.Van der Waals interactions play an important role in inclusion complexes of cryptophane-C with chloroform or dichloromethane. The complex formation was thoroughly investigated by means of 1H and 13C NMR experiments along with the quantum-chemical density functional theory (DFT) calculations. We characterized kinetics, thermodynamics, as well as fine details of structural rearrangements of the complex formation.Internal dynamics of oligo- and polysaccharides presents a considerable challenge due to possible coupling of internal and global molecular motions. Two small oligosaccharides were investigated as test cases for a newly developed integrated approach for interpreting the dynamics of the molecules with non-trivial internal flexibility. The approach comprised advanced theoretical tools, including stochastic modeling, molecular dynamics (MD) simulations, and hydrodynamic simulations.A biologically important bacterial O-antigenic polysaccharide from E. Coli O91 was addressed employing selective isotope labeling and multiple-field 13C relaxation experiments. The complex dynamics of the polysaccharide is characterized by the conformational motion of the exocyclic groups of the sugars, superimposed to the breathing motion of the polymeric chain.Hydrogen bonding is another major non-covalent interaction. Dilute solutions of ethanol were chosen as a model of liquid systems containing extensive hydrogen-bonded networks. We developed a new methodology consisting of NMR diffusion measurements, DFT calculations, and hydrodynamic modeling and utilized it to determine average size of the molecular clusters of ethanol at given conditions.
|
|
| 6. |
- Takacs, Zoltan, 1982-
(author)
-
Chloromethane Complexation by Cryptophanes : Host-Guest Chemistry Investigated by NMR and Quantum Chemical Calculations
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Host–guest complexes are widely investigated because of their importance in many industrial applications. The investigation of their physico–chemical properties helps understanding the inclusion phenomenon. The hosts investigated in this work are cryptophane molecules possessing a hydrophobic cavity. They can encapsulate small organic guests such as halo–methanes (CH2Cl2, CHCl3). The encapsulation process was investigated from both the guest and the host point of view. With the help of Nuclear Magnetic Resonance (NMR), the kinetics of complex formation was determined. The information was further used to obtain the activation energies of the processes. Having done this on five different cryptophanes, it is possible to relate the energies to structural differences between the hosts. Via the dipolar interaction between the guest’s and host’s protons, one can get information on the orientation of the guest inside the cavity. Moreover, the dynamics of the guest can be further investigated by its relaxation properties. This revealed restricted motion of the guest inside the host cavity. Not only the nature of the guest plays an important role. The host is also changing its properties upon encapsulation. All the cryptophanes investigated here can exchange rapidly between many conformers. These conformers have different–sized cavities. Quantum chemical optimization of the structure of the conformers makes volume estimation possible. Not only the cavity volumes, but also the quantum-chemically obtained energies and the calculated chemical shifts of the carbon–13 atoms can be helpful to follow the changes of the host upon complex formation. The host cannot be considered as a rigid entity. Analysis of variable temperature proton and carbon-13 spectra shows that the encapsulation can be considered as a mixture of conformational selection and induced fit. The structures of the formed complexes are further investigated by means of two-dimensional nuclear Overhauser spectroscopy (NOESY). The complex formation, its kinetics and thermodynamics are found to be a complicated function of structure elements of the host, the cavity size and the guest size and properties.
|
|
| 7. |
- Zhou, Xiangzhi, 1975-
(author)
-
An Analysis of NMRD profiles and ESR lineshapes of MRI Contrast Agents
- 2004
-
Doctoral thesis (other academic/artistic)abstract
- To optimize contrast agent in MRI scan region, e.g. to enhance paramagnetic relaxation in the MRI scan fields(0.1T-3T), one possible way is to slow down the tumbling of the paramagnetic complex. The effect of slowing down the reorientational motion of the complex to increase relaxivity is obvious and this strategy has already been employed in producing MRI contrast agent that can bind to specific proteins. An example is MS-325 binds to human serum albumin(HSA). The slow down effects on the ligands around paramagnetic ion, and on the zero field splitting(ZFS) interaction are under studies and the physics behind is still not clear. In this thesis, a generalized Solomon-Bloembergen-Morgan(GSBM) theory together with stochastic Liouville approach(SLA), is applied to investigate the mechanism behind the slow down effects. Two gadolinium complexes, MS-325+HSA and Gd(H2O)83++glycerol are studied by means of NMRD and ESR experiments.GSBM is a second order perturbation theory with closed analytical form. The computation based on this theory is fast, but it has its limitation and in the case of Gd(S=7/2) the ZFS strength times its correlation time(Δt.τƒ) should be less than 0.1. In comparison, the SLA is an "exact" theory that can evaluate the validity of GSBM calculation. However, the calculation in SLA is time consuming due to the large matrix it constructed. The major model used in GSBM is a two dynamic model, characterized by transient ZFS Δt and static ZFS Δs and their corresponding correlation time τƒ and τR, while in SLA the model is only described by Δt and τƒ. A combined NMRD and ESR analysis is used to understand the details of ZFS interaction. Both models can reproduce experimental NMRD profiles and model parameters are similar; for ESR linewidths the model parameters are quite different. The fitting results indicate the NMRD profiles are less sensitive to the detail expression of ZFS correlation function. In order to interpret both NMRD and ESR experiments with identical parameters, a more complex ZFS interaction model should be developed.
|
|
