Room Temperature Chiral Discrimination in Paramagnetic NMR Spectroscopy

Abstract

A recently proposed theory of chiral discrimination in NMR spectroscopy based on the detection of a molecular electric polarization P rotating in a plane perpendicular to the NMR magnetic field [A. D. Buckingham, J. Chem. Phys. 140, 011103 (2014)], is here generalized to paramagnetic systems. Our theory predicts new contributions to P , varying as the square of the inverse temperature. Ab initio calculations for ten Dy 3+ complexes, at 293K, show that in strongly anisotropic paramagnetic molecules P can be more than 1000 times larger than in diamagnetic molecules, making paramagnetic NMR chiral discrimination amenable to room temperature detection.Despite its central role in biological processes and in a wide range of chemical reactions, chirality, the property of molecules lacking improper symmetry elements to be distinguishable from their mirror image (or enantiomer), remains a challenging property to detect and quantify [1], making the development of new spectroscopic techniques to achieve this goal a strategic research field [2-9].Magnetic resonance spectroscopies, despite being among the most useful characterization techniques due to their high sensitivity to tiny details of the geometrical and electronic structure of molecules, are blind to chirality. However, it has been recently proposed by Buckingham [3,9] and Fischer [5] that NMR could be used to achieve chiral discrimination for closed-shell chiral molecules via a minor modification of the experimental set up, so to make it fit for the detection of a rotating average electric polarization P induced by the combined effect of the NMR magnetic field B, and the nuclear magnetic dipole moment m I associated to a nucleus I of the chiral molecule, rotating in the plane perpendicular to B following a resonant π/2 radiofrequency pulse. In particular, the induced P is always oriented along B × m I (thus rotating with m I ), points in opposite directions for the two enantiomers (hence its chirality-sensitivity), and is proportional to the pseudoscalar σ (1) , isotropic average of a third-rank tensor σ ijk (i, j, k = x, y, z) known as shielding polarizability [3, 5,10]. However, computational estimates of σ (1) in diamagnetic molecules suggest that it is generally too small to be detected [9,11,12].In this Letter we propose a theory of paramagnetic NMR chiral discrimination which is valid for molecules with a ground state of arbitrary degeneracy. We describe the response of the degenerate system in terms of a generalized shielding polarizability tensor Φ ijk defined by analytical third-derivatives of the free energy, reducing to σ ijk in the limit of a non-degenerate ground state. The proposed free-energy response theory features previously unexplored terms proportional to the square of the inverse temperature β = 1/k B T , so that σ (1) becomes σ (1) + β 2 σ (1p) . Finally, we present ab initio calculations showing that β 2 σ (1p) yields a contribution to P at 293K that is orders of magnitude larger than in closed-shell molecules, potentially observable at room...

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“…Having a very high magnetic susceptibility tensor anisotropy, which is a prerequisite for the SMM behavior, these cobalt(II) complexes can also be used as paramagnetic tags for structure determination of biological macromolecules 39,40 (such as cholesterol-binding proteins 41 ) or as model compounds for chiral discrimination by NMR spectroscopy. 42…”

Antisymmetric Couplings Enable Direct Observation of Chirality in Nuclear Magnetic Resonance Spectroscopy

“…Because antisymmetric Jcouplings are similar in magnitude to the isotropic rank-0 term, 26,27 we assume a residual J xy of 1 Hz, corresponding to a orientational order parameter of ∼10 −2 , typical of electric-field orientation experiments. 32 For a one-bond 13 C− 1 H coupling with this degree of orientation, the alignment induced by the electric field results in a residual dipolar coupling of ∼0.7 Hz (see the Supporting Information). Oscillating magnetization emerges along the x axis with the sign of the signal determined by the sign of J xy (Figure 3a,b), thereby distinguishing right and left enantiomers.…”

“…Several proposals exist for direct observation of chirality via an electric-field-induced pseudoscalar term in the NMR Hamiltonian. These involve either the detection of an induced oscillating molecular electric dipole moment [11][12][13][14] or a magnetic dipole signal induced via application of an electric field [15][16][17].…”

“…Several proposals exist for direct observation of chirality via an electric-field-induced pseudoscalar term in the NMR Hamiltonian. These involve either the detection of a chiral nuclear magnetic shielding via induced oscillating molecular electric dipole moment − or a magnetic dipole signal-induced via application of an electric field. − Chiral effects may also manifest in the electric polarizability of the spin–spin J -coupling …”

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