Residual quadrupolar couplings contain important structural information comparable with residual dipolar couplings. However, the measurement of sign and size of especially small residual quadrupolar couplings is difficult. Here, we present an extension of the E.COSY principle to spin systems consisting of a Spin 1 coupled to a spin ½ nucleus, which allows the determination of the sign of the quadrupolar coupling of the Spin 1 nucleus relative to the heteronuclear coupling between the spins. The so-called Q.E.COSY approach is demonstrated with its sign-sensitivity using variable angle NMR, stretched gels and liquid crystalline phases applied to various CD and CD₃ groups. Especially the sign-sensitive measurement of residual quadrupolar couplings that remain unresolved in conventional deuterium 1D spectra is shown. Copyright © 2016 John Wiley & Sons, Ltd.

Residual dipolar couplings are highly useful NMR parameters for calculating and refining molecular structures, dynamics, and interactions. For some applications, however, it is inevitable that the preferred orientation of a molecule in an alignment medium is calculated a priori. Several methods have been developed to predict molecular orientations and residual dipolar couplings. Being beneficial for macromolecules and selected small-molecule applications, such approaches lack sufficient accuracy for a large number of organic compounds for which the fine structure and eventually the flexibility of all involved molecules have to be considered or are limited to specific, well-studied liquid crystals. We introduce a simplified model for detailed all-atom molecular dynamics calculations with a polymer strand lined up along the principal axis as a new approach to simulate the preferred orientation of small to medium-sized solutes in polymer-based, gel-type alignment media. As is shown by a first example of strychnine in a polystyrene/CDCl₃ gel, the simulations potentially enable the accurate prediction of residual dipolar couplings taking into account structural details and dynamic averaging effects of both the polymer and the solute. Copyright © 2015 John Wiley & Sons, Ltd.

Fast measurement of heteronuclear one-bond couplings, a class of NMR parameters valuable for structure elucidation, is highly desirable, especially if samples undergo chemical reactions or dynamic processes are observed. Methods presented so far face severe limitations in terms of resolution, accessible bandwidth, and sensitivity. We present the CLean InPhase-Acceleration by Sharing Adjacent Polarization-HSQC (CLIP-ASAP-HSQC) pulse sequence that allows fast acquisition of spectra with clean inphase multiplets in about 25 s. The performance in terms of accurate extraction of one-bond couplings is demonstrated on three test samples including partially aligned molecules. Copyright © 2015 John Wiley & Sons, Ltd.

Pulse sequences in NMR spectroscopy sometimes require the adjustment of effective flip angles with respect to experiment-specific or sample-specific parameters. Here, we present a quality factor for efficient optimization of offset-compensated broadband excitation pulses with RF amplitude-dependent effective flip angles (RADFA). After proof of principle, physical limits of RF amplitude-restricted and RF power-restricted broadband RADFA pulses are explored and corresponding pulse shapes and performances characterized in detail. Copyright © 2015 John Wiley & Sons, Ltd.

Heteronuclear TOCSY (HEHAHA) experiments for ¹H,⁶Li spin pairs in organolithium compounds with adjacent strongly coupled ¹H,¹H spin systems showed unexpected cross peak behaviour: for n-butyllithium ¹H,⁶Li cross peaks were completely missing, whereas for the dimer of (Z)-2-lithio-1-(o-lithiophenyl)ethane, a cross peak for remote protons was observed even at very short mixing times. It was assumed that strong magnetization transfer within the proton spin systems was responsible for these results, which prevented unambiguous chemical shift assignments. Selective experiments with the ⁶Li,¹H-HET-PLUSH-TACSY sequence then showed the expected ⁶Li,¹H cross peaks for the transfer via the directly coupled ¹H and ⁶Li nuclei. For n-butyllithium transfer to H(C_α) via an unresolved heteronuclear coupling constant below 0.1 Hz is unambiguously observed. Cross peaks in the 2D ⁶Li,¹H-HET-PLUSH-TACSY spectra for the dimer of (Z)-2-lithio-1-(o-lithiophenyl)ethane are readily explained by the measured coupling network and the corresponding active mixing conditions. Copyright © 2014 John Wiley & Sons, Ltd.

Deuterium NMR imaging was used to evaluate the spatial distribution of the degree of alignment in different types of alignment media by monitoring the deuterium quadrupolar splitting using spatially resolved NMR techniques in conventional liquid state NMR instruments. These images allow the unambiguous distinction of magnetic field and alignment inhomogeneities present in partially aligned samples, revealing the underlying reasons for linebroadening within an alignment medium that cannot be explained by the sole analysis of 1D ²H NMR spectra. For example, alignment inhomogeneities due to broken gels or the presence of concentration gradients in liquid crystalline solutions are clearly detected by the imaging methods proposed in this work.

Robust experiments that cover a wide range of chemical shift offsets and J-couplings are highly desirable for a multitude of applications in small molecule NMR spectroscopy. Many attempts to improve individual aspects of the robustness of pulse sequence elements based on rational and numerical design have been reported, but a general optimization strategy to cover all necessary aspects for a fully robust sequence is still lacking.

In this article, a viable optimization strategy is introduced that covers a defined range of couplings, offsets, and B₁-field inhomogeneities (COB) in a time-optimal way. Individual components of the optimization strategy can be optimized in any adequate way. As an example for the COB approach, we present the ¹H − ¹³C-COB-INEPT with transfer of approximately 99% over the full carbon and proton bandwidth and ¹J_CH-couplings in the range of 120–250 Hz, which have been optimized using efficient algorithms derived from optimal control theory. The theoretical performance is demonstrated in a number of corresponding COB-HSQC experiments. Copyright © 2012 John Wiley & Sons, Ltd.

Heteronuclear one-bond couplings have a variety of applications, and their accurate determination is the basis for obtaining specific structural information of mostly small organic compounds. In this context, it is of utmost importance to reduce signal overlap to a minimum, and a number of techniques has been introduced during the last decades. Here, we introduce a modified version of the HR-HMBC (Magn. Reson. Chem. 2010, 48, 179-183) for heteronuclear one-bond coupling measurements with improved resolution because of the J-resolved-like tilt of corresponding multiplet patterns. The pulse sequence is introduced, and its performance is compared with a standard ω₂-coupled HSQC experiment. Example spectra on glucose and maltose demonstrate that signals can be resolved that overlap otherwise. The approach is discussed in detail. Copyright © 2012 John Wiley & Sons, Ltd.