Design of Novel NMR Methodologies to address diverse challenging problems in Chemistry

Abstract

The thesis entitled “Design of Novel NMR Methodologies to address diverse challenging problems in Chemistry” discusses the design of number of novel NMR methodologies which have broader utility and, also the extensive investigations carried out on the weak molecular interactions like Hydrogen bonding. The applications of the novel sequences to address various challenging problems encountered in chemistry have been demonstrated. The first part of the thesis discusses the manipulation of the spin dynamics for the development of two novel NMR methodologies. The first developed methodology is cited as PASS-J¬-Resolved, which is used for the extraction of the scalar coupling information for a selected proton along with combating the inherent sensitivity issue of Clean-G-SERF experiment. Unlike Clean-G-SERF experiment, the new sequence not only yields the active couplings, but also the passive coupling information. Further, to enhance the resolution of PASS-J-Resolved experiment, another experiment cited as PASS-J-Resolved-NOAP has been developed in which the final spectrum is obtained from the inphase terms which yield the spectrum with enhanced resolution. The distinct advantages of these experimental techniques have been demonstrated by extracting the coupling information for a selected proton from the complex spectra of β-butyrolactone and strychnine. Another new pulse sequence developed is the Phase Modulated (PM) one-dimensional TOCSY. The phase modulation of the chosen spin relative to other spins can be achieved by appropriate manipulation of the delay period before the isotropic mixing. It helps to differentiate different spin systems, based on the 180-degree phase difference between the selectively excited proton with the remaining spins or by nullifying the signal of the chosen spin. The wide utility of this methodology has been demonstrated on; the spin systems identification in a multicomponent mixture, identification of α- and β- anomers of glucose and suppression of residual water peak and providing the solution for enantiomeric discrimination in challenging situations. In another direction, the investigations on the hydrogen bond (HB) have been carried out by the extensive utility of NMR experiments on the synthesised binaphthalene benzamide derivatives. The application of various multinuclear and multidimensional NMR experiments indubitably established the existence of HB in all the synthesised molecules. Two-dimensional experiments like HOESY on the fluorine substituted molecule confirmed the close spatial proximity between 19F and 1H, conducive for HB interactions. The 15N-1H HSQC experiment aided in the determination of both scalar couplings and the couplings mediated through HB. All the NMR experimental findings are corroborated by theoretical computations, using DFT based approaches, such as, QTAIM and NCI. Single crystal XRD structure of the fluoro-derivative is also obtained which aided in ascertaining the spatial proximity between the fluorine and hydrogen atom, and confirmed the NMR observations. From the XRD structure, the reason for the retention of strong HB in the high polarity solvents like DMSO-d6 has been understood.