Chiral discrimination in nuclear magnetic resonance spectroscopy

Abstract

Chirality is a fundamental property of molecules whose spatial symmetry is characterized by the absence of improper rotations, making them not superimposable to their mirror image. Chiral molecules constitute the elementary building blocks of living species and one enantiomer is favoured in general (e.g. L-aminoacids and D-sugars pervade terrestrial homochiral biochemistry) because most chemical reactions producing natural substances are enantioselective. Since the effect of chiral chemicals and drugs on living beings can be markedly different between enantiomers, the quest for practical spectroscopical methods to scrutinize chirality is an issue of great importance and interest. Nuclear magnetic resonance (NMR) is a topmost analytical technique, but spectrometers currently used are 'blind' to chirality, i.e. unable to discriminate the two mirror-image forms of a chiral molecule, because, in the absence of a chiral solvent, the spectral parameters, chemical shifts and spin-spin coupling constants are identical for enantiomers. Therefore, the development of new procedures for routine chiral recognition would offer basic support to scientists. However, in the presence of magnetic fields, a distinction between true and false chirality is mandatory. The former epitomizes natural optical activity, which is rationalized by a time-even pseudoscalar, i.e. the trace of a second-rank tensor, the mixed electric dipole/magnetic dipole polarizability. The Faraday effect, magnetic circular dichroism and magnetic optical activity are instead related to a time-odd axial vector. The present review summarizes recent theoretical and experimental efforts to discriminate enantiomers via NMR spectroscopy, with the focus on the deep connection between chirality and symmetry properties under the combined set of fundamental discrete operations, namely charge conjugation, parity (space inversion) and time (motion) reversal.

Highlighting spin selectivity properties of chiral electrode surfaces from redox potential modulation of an achiral probe under an applied magnetic field

“…Importantly, only when interacting with a truly chiral system the energy of enantiomeric probes can be different (corresponding to diastereomeric situations), while no loss of degeneration in energy levels can happen in a falsely chiral system; however, asymmetry could be obtained for processes out of thermodynamic equilibrium 27. Consistent with Barron's rationale, a magnetic field alone cannot produce true chirality, as already stated by Lord Kelvin in 1904,28 not even, in spite of an early assumption by Pierre Curie,28 upon addition of a collinear, uniform and constant electric field, a combination which, as more recently demonstrated,30 cannot affect the enantiomer equidistribution in a racemate at equilibrium. Instead, according to Barron's approach, an electron in helical roto-translational motion with spin–orbit coupling ( i.e.…”

Physical achirality in geometrically chiral rotamers of hydrazine and boranylborane molecules

“…Capitals denote n ‐electron vector operators, for example, for position, canonical, and angular momentum, except for the electric and magnetic dipoles, 49–51 …”

“…The static anapole magnetizability a αβ is a nonsymmetric parity‐odd, time‐even, second‐rank tensor, expressed as the sum of paramagnetic and diamagnetic contributions, 51,53–58 …”

“…The sum rule 51 arrived at by summing the terms in the numerator of Equation (6), corresponds to the Condon sum rule 59 for rotational strengths R aj , useful to check the accuracy of computed mixed electric‐dipole magnetic‐dipole polarisability, defined by the nonsymmetric parity‐odd, time‐even, second‐rank tensor, 49–51 …”

Direct distinction of ibuprofen and flurbiprofen enantiomers by ion mobility mass spectrometry of their ternary complexes with metal cations and cyclodextrins in the gas phase

“…Many technologies and methods have been developed for enantioselective analysis, including HPLC [11][12][13][14], CE [15][16][17][18], GC [19,20], supercritical fluid chromatography [21], and nuclear magnetic resonance (NMR) [22,23]. These methods have been widely applied and intensively investigated and developed over the past several decades.…”