Development and Evaluation of Experiments for Pure Shift Solution-State Magnetic Resonance Spectroscopy

• Main Author: Kaltschnee, Lukas
• Format: Others
• Language: en
• Published: 2016
• Online Access: https://tuprints.ulb.tu-darmstadt.de/5650/7/20160826_Diss_Kaltschnee.pdf; https://tuprints.ulb.tu-darmstadt.de/5650/8/supplementary_material.zip; Kaltschnee, Lukas <http://tuprints.ulb.tu-darmstadt.de/view/person/Kaltschnee=3ALukas=3A=3A.html> (2016): Development and Evaluation of Experiments for Pure Shift Solution-State Magnetic Resonance Spectroscopy.Darmstadt, Technische Universität, [Ph.D. Thesis]

Nuclear Magnetic Resonance Spectroscopy (NMR) nowadays is one of the most versatile tools for chemists to study molecular structure and dynamics in solution. The unique feature of this spectroscopic method is that different NMR experiments, by means of different NMR pulse sequences, can be used to collect various information about atomic connectivity, molecular geometry and molecular dynamics, mostly using a single sample and a single spectrometer. This thesis reports on NMR pulse sequence developments leading to homonuclear broadband decoupled NMR spectra, a field of work which recently attracted renewed attention as the field of “pure shift NMR”. The experiments developed in this work enable the extraction of NMR structure parameters from spectra with simplified signal appearance. The work is separated in four distinct projects: In project A it is shown, that the extraction of interatomic distances, via the nuclear Overhauser effect (NOE), is possible from pure shift NOESY and pure shift 1D NOE experiments in a quantitative fashion. Requirements for unbiased distance measurements from pure shift spectra and factors possibly limiting the accuracy of the measurement are discussed. Project B describes the development and testing of pure shift HSQC experiments, based on CLIP/CLAP-HSQC experiments, designed for accurate measurement of one-bond residual dipolar couplings (RDCs). All experiments described in this chapter enable the extraction of the heteronuclear coupling constants 1J(XH) and 1T(XH) in the high-resolution proton dimension, which features partial or full suppression of homonuclear coupling pattern. It is shown, that the CLIP/CLAP-HSQC experiments with F2-BIRD and F2-perfectBIRD homonuclear decoupling presented enable high-accuracy measurement of one-bond RDCs. Further, F2-real-time-BIRD homonuclear decoupled CLIP/CLAP-HSQC experiments are presented, which enable the measurement for one-bond RDCs in experiments with instant homonuclear decoupling. Project C makes direct use of the perfectBIRD decoupling scheme derived in project B. A fully homo- and heteronuclear decoupled F2-perfectBIRD HSQC experiment is presented, which is tailored for highest field strengths available. This experiment provides direct access to HSQC correlation information with notably good signal separation, which is demonstrated in the case study of an oligomeric urea-derivative, normally leading to heavily overlapped spectra. Project D presents a practical solution to the long-standing problem of recording COSY-type correlation spectra with in-phase absorptive signal appearance. The CLIP-COSY experiment presented achieves these desirable spectral features even with a single scan per t1-increment and thus provides rapid access to COSY-type spectra with simple signal appearance along both spectral dimensions. The robustness of the experiment, e.g. towards signal loss in the case of line broadening, and the possibility of combining the experiment with pure shift acquisition techniques are presented.