N. Suryaprakash

Spin selective multiple quantum NMR for spectral simplification, determination of relative signs, and magnitudes of scalar couplings by spin state selection

In the present work we demonstrate a novel method for spectral simplification and determination of the relative signs of the scalar couplings using a spin selective multiple quantum NMR experiment. A spin selective excitation of double quantum coherence of A and M spins in a weakly coupled three spin system of the type AMX, results in a doublet in the double quantum dimension whose separation corresponds to the sum of couplings of the active spins to the passive spin X. One component of the doublet has the passive spin X in mid R:alpha state while the other component has the passive spin X in mid R:beta state. The spin selective conversion of double quantum coherence to single quantum coherence does not disturb the spin states of the passive spin thereby providing the spin state selection. There will be two domains of single quantum transitions in single quantum dimension at the chemical shift positions of A and M spins. The mid R:alpha domain of A spin is a doublet because of mid R:alpha and mid R:beta states of M spin only, while that of mid R:beta domain is another doublet in a different cross section of the spectra. The scalar coupling J(AM) can be extracted from any of the mid R:alpha and mid R:beta domain transitions while the relative displacements of the two doublets between the two domains at the two chemical shifts provides the magnitude and sign of the scalar coupling J(AX) relative to the coupling J(MX). Similar result is obtained for zero quantum studies on AMX spin system. The proposed technique is discussed theoretically using product operator approach. The new spin state selective double quantum J-resolved sequence has also been developed. The methodology is confirmed experimentally on a homonuclear weakly coupled three spin system and applied to two different heteronuclear five spin systems.

Discerning the degenerate transitions of scalar coupled 1H NMR spectra: Correlation and resolved techniques at higher quantum

The blend of spin topological filtering and the spin state selective detection of single quantum transitions by the two dimensional multiple quantum-single quantum correlation and higher quantum resolved techniques have been employed for simplifying the complexity of scalar coupled (1)H NMR spectra. The conventional two dimensional COSY and TOCSY experiments, though identify the coupled spin networks, fail to differentiate them due to severe overlap of transitions. Non-selective excitation of homonuclear higher quantum of protons results in filtering of spin systems irrespective of their spin topologies. The spin state selection by passive (19)F spins provides fewer transitions in each cross section of the single quantum dimension simplifying the analyses of the complex spectra. The degenerate single quantum transitions are further discerned by spin selective double and/or triple quantum resolved experiments that mimic simultaneous heteronuclear and selective homonuclear decoupling in the higher quantum dimension. The techniques aided the determination of precise values of spectral parameters and relative signs of the couplings.

Binuclear spin state selective detection of 1H single quantum transitions using triple quantum coherence: a novel method for enantiomeric discrimination.

In the present work a novel methodology is developed for the unambiguous discrimination of enantiomers aligned in chiral liquid crystalline media and the simultaneous determination of 1H-1H and 13C-1H couplings in a single experiment. An INEPT transfer and back transfer of magnetization to protons retain the 13C edited 1H magnetization which is utilized to generate spin selective homonuclear triple quantum coherence of dipolar coupled methyl protons. Spin selective correlation of triple quantum to single quantum coherence results in spin state selective detection by 13C spin and the remaining passive protons. The difference between the successive transitions in the triple quantum dimension pertains to sum of the passive couplings and results in enhanced resolution by a factor of three. This results in unambiguous chiral visualization. The masked 13C satellite transitions in the single quantum spectrum are extracted for chiral discrimination. The technique retains all the passive homo- and heteronuclear couplings in the triple quantum dimension by the application of non-selective refocusing pulse on 1H as well as on 13C spins. This, however, refocuses the chemical shift evolution in the triple quantum dimension, and also overcomes the problem of field inhomogeneity. The method enables the determination of spectral information which is otherwise not possible to derive from the broad and featureless proton spectra. The elegant experimental technique has been demonstrated on different chiral molecules.

Spin state selective coherence transfer: a method for discrimination and complete analyses of the overlapped and unresolved 1H NMR spectra of enantiomers.

In general, the proton NMR spectra of chiral molecules aligned in the chiral liquid crystalline media are broad and featureless. The analyses of such intricate NMR spectra and their routine use for spectral discrimination of R and S optical enantiomers are hindered. A method is developed in the present study which involves spin state selective two dimensional correlation of higher quantum coherence to its single quantum coherence of a chemically isolated group of coupled protons. This enables the spin state selective detection of proton single quantum transitions based on the spin states of the passive nuclei. The technique provides the relative signs and magnitudes of the couplings by overcoming the problems of enantiomer discrimination, spectral complexity and poor resolution, permitting the complete analyses of the otherwise broad and featureless spectra. A non-selective 180 degrees pulse in the middle of MQ dimension retains all the remote passive couplings. This accompanied by spin selective MQ-SQ conversion leads to spin state selective coherence transfer. The removal of field inhomogeneity contributes to dramatically enhanced resolution. The difference in the cumulative additive values of chemical shift anisotropies and the passive couplings, between the enantiomers, achieved by detecting Nth quantum coherence of N magnetically equivalent spins provides enhanced separation of enantiomer peaks. The developed methodology has been demonstrated on four different chiral molecules with varied number of interacting spins, each having a chiral centre.

Band selective small flip angle COSY: A simple experiment for the analyses of 1H NMR spectra of small chiral molecules

The NMR spectroscopic discrimination of enantiomers in the chiral liquid crystalline solvent is more often carried out using (2)H detection in its natural abundance. The employment of (1)H detection for such a purpose is severely hampered due to significant loss of resolution in addition to indistinguishable overlap of the spectra from the two enantiomers. This study demonstrates that the band selected small flip angle homonuclear correlation experiment is a simple and robust technique that provides unambiguous discrimination, very high spectral resolution, reduced multiplicity of transitions, relative signs of the couplings and enormous saving of instrument time.

Chapter 4 Analyses of Proton NMR Spectra of Strongly and Weakly Dipolar Coupled Spins: Special Emphasis on Spectral Simplification, Chiral Discrimination, and Discerning of Degenerate Transitions

Abstract The 1 H NMR spectra of partially aligned molecules become rapidly complex with the increase in the number of interacting spins and the decrease in the symmetry of the molecules. In the strongly orienting thermotropic liquid crystals, the analyses of the complex spectra are very challenging due to their second-order character. The numerical iterative calculations that are generally employed for such analyses are tedious and time consuming. On the other hand, in weakly ordering media such as bicelles or in chiral liquid crystal solvent poly-γ-benzyl- l -glutamate (PBLG), the spin systems are weakly coupled and the first-order analysis is generally possible. However, for the chiral molecules aligned in the chiral liquid crystal medium, the 1 H NMR spectra are not only complex, but also broad and featureless due to large number of pair-wise interactions of nuclear spins resulting in degenerate or near-degenerate transitions, in addition to an indistinguishable overlap of the spectra of enantiomers. This enormous loss of resolution severely hampers the analyses of proton spectra, even for spin systems with five to six interacting protons, thereby restricting its routine application. In this chapter, we report the diverse methods available to circumvent the difficulties in the analyses of such spectra, in both strongly and weakly orienting media. The discussion is devoted to recent methodological developments in the context of spectral simplification, chiral discrimination, and the discerning of the degenerate transitions.

Chemical shift anisotropy edited complete unraveling of overlapped 1H NMR spectra of enantiomers: Application to small chiral molecules

The differential values of NMR spectral parameters like chemical shift anisotropies, dipolar couplings and quadrupolar couplings of enantiomers in chiral liquid crystalline media are employed not only for their visualization but also for their quantification. Large differences in chemical shift anisotropies and the quadrupolar couplings between the enantiomers enable the use of 13C and extensive 2H NMR detection for such a purpose. In spite of high magnetic moment, high sensitivity and abundant presence of protons in all the chiral molecules, 1H detection is not routinely employed due to severe overlap of unresolved transitions arising from short and long distance couplings. Furthermore, the doubling of the spectra from two enantiomers and their indistinguishable overlap due to negligible difference in chemical shift anisotropies hampers their discrimination. The present study demonstrates the use of proton chemical shift anisotropy as an exclusive parameter for such a discrimination. The method employs the non-selective excitation of homonuclear Nth quantum coherence of N coupled protons. The simultaneous flipping of all the coupled spins results in a single transition in the multiple quantum dimension at the cumulative sum of their anisotropic chemical shifts for each enantiomer, with the measurable difference between them, resulting in their complete unraveling.

“Near magic angle” sample spinning in NMR spectra of molecules oriented in individual and mixed liquid crystals of opposite diamagnetic anisotropies

The dynamics of the liquid crystal director in “near magic angle” sample spinning has been investigated in mesophases with positive and negative diamagnetic susceptibility anisotropies and their mixtures with near-zero macroscopic diamagnetic anisotropy. To this end the deuteron quadrupolar splitting of deuterochloroform dissolved in liquid crystals has been monitored. In systems with weakly positive diamagnetic susceptibility anisotropy (Δχ), the director has been observed to switch from an orientation parallel to the spinning axis at low rotational speeds to one perpendicular to the spinning axis at high rotational speeds when the angle (θ) the axis of rotation makes with the magnetic field is smaller than the magic angle (θm). For systems with a small negative Δχ similar director behaviour has been observed for θ greater than θm.

Spin-selective multiple quantum excitation: Relative signs of the couplings and ambiguous situations

Homonuclear higher quantum NMR spectra of heteronuclear spin systems result in fewer transitions aiding the analyses. In such experiments the spin states of the heteronuclei do not get disturbed in both single and multiple quantum dimensions resulting in the separation of active homonuclear and passive heteronuclear couplings in two dimensions. The cross sections of the single-quantum dimension get displaced according to the strengths of the passive couplings. The directions of the displacement of these cross sections provide relative signs among the passive couplings. The present study demonstrates the situations when the displacement vectors, though provide the relative signs, could be ambiguous. The dynamics of the spin systems in homo- and heteronuclear multiple quantum studies have been discussed using polarization operator approach. The experimental results on (13)C- and (15)N-labeled isotopomers of acetonitrile, in both isotropic and thermotropic liquid crystalline phases, are reported.

Chiral discrimination of secondary alcohols and carboxylic acids by NMR spectroscopy.

The manuscript reports two novel ternary ion‐pair complexes, which serve as chiral solvating agents, for enantiodiscrimination of secondary alcohols and carboxylic acids. The protocol for discrimination of secondary alcohols is designed by using one equivalent mixture each of enantiopure mandelic acid, 4‐dimethylaminopyridine (DMAP) and a chiral alcohol. For discrimination of carboxylic acids, the ternary complex is obtained by one equivalent mixture each of enantiopure chiral alcohol, DMAP and a carboxylic acid. The designed protocols also permit accurate measurement of enantiomeric composition. Copyright