New Tools in Bio-NMR: Indirect Detection of Nitrogen-14 in Solids

Abstract

Nnuclei.Thetwo-dimensionalcorrelationmethodspresentedherearecloselyrelatedtothewellknownheteronuclearsingle-andmultiple-quantumcorrelation(HSQCandHMQC,respectively)experiments, alreadywidelyusedfortheinvestigationofmoleculesinliquids.Nitrogen-14NMRspectraexhibitpowderpat-ternscharacterizedbysecond-andthird-orderquadrupolarcouplingswhichcanprovideimportantinformation aboutstructureanddynamicsofmoleculesinpowdersamples.

Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs

“…48,77 A variety of techniques have been explored for the acquisition of 14 N SSNMR spectra, including the direct observation of 14 N NMR signals from single crystals, 78 14 N magic-angle spinning (MAS) NMR using specialized probes with precisely tuned rotor angles, 56,79 overtone 14 N MAS NMR, 80-83 14 N NMR enhanced by dynamic nuclear polarization (DNP), 84 and various indirect detection techniques. [85][86][87][88][89] However, many of these techniques have not been widely adopted thus far owing to technical difficulties, costly hardware, and/or issues relating to the nature of the nitrogen sites in samples under investigation. O'Dell and Cavadini recently provided thorough reviews of 14 N SSNMR experiments involving direct and indirect detection, respectively.…”

An efficient NMR method for the characterisation of 14N sites through indirect 13C detection

“…More recently however a class of MAS experiments has been proposed which utilizes a proximal spy nucleus, typically 13 C or protons, to probe the spectral properties of an adjacent 14 N site. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Experiments utilizing these 'spy' nuclei approach lead to the indirect detection of the 14 N signal and are loosely based on the analogous liquid-state HMQC and HSQC experiments. However in this instance, coherence between the 14 N and the spy nuclei is mediated not only by the J-coupling but also by the secondorder quadrupolar-dipolar interactions, sometimes referred to as the residual dipolar splittings, which are not completely averaged by MAS, 23 and by the dipole-dipole interaction if suitable recoupling methods are adopted.…”

Dynamic Nuclear Polarization and Other Magnetic Ideas at EPFL

“…Even when spinning rapidly, 14 N spectra often feature dozens of spinning sidebands, [50] rendering their excitation and detection very challenging. We therefore developed methods that combine MAS with indirect detection of 14 N via neighbouring spy nuclei with a more favourable spin S = ½ such as 1 H or 13 C. [51][52][53][54] These methods are closely related to the well-known heteronuclear single-and multiple-quantum correlation experiments (HSQC and HMQC) in liquids. Indirect detection of 14 N in solids was used to study local dynamics in peptides and revealed motions on time-scales near 10 -7 s that had never been observed before by NMR.…”