ASAP - Acceleration by Sharing Adjacent Polarization

NMR is a non destructive technique and so reducing acquisition time can be used either to increase sample throughput, or to lower the detection limit. To lower the detection limit a given amount of time is used to acquire a greater number of scans than would normally be acquired. A relatively recent method for reducing acquisition time is ASAP (Acceleration by Sharing Adjacent Polarization)¹. The ASAP technique speeds acquisition by greatly reducing the length of the relaxation delay.

Pure shift NMR - Broad band homodecoupled HSQC

In most 2D NMR spectra the position of the peaks, the chemical shift, is the most important piece of information. If splitting of the peaks by scalar coupling is observed, it is usually ignored. In fact, in many cases scalar coupling in 2D experiments can be detrimental. The splitting increases the chance of overlap and makes it harder to determine accurately the chemical shift. Pure shift experiments, in which the scalar coupling is removed, do not have these problems and are also more sensitive because the peaks are narrower and taller. Heteronuclear 2D experiments, such as HSQC, can be converted to pure shift experiments without loss of sensitivity by applying broad band homo decoupling during acquisition.

Pure Shift NMR - PSYCHE

Pure shift NMR spectra are spectra in which the scalar coupling has been removed so that all signals appear as singlets, as in 1D ¹³C spectra. For ¹³C spectra the coupling is removed by applying ¹H composite pulse decoupling during acquisition. Acquiring a pure shift ¹H spectrum, however, is not so easy because applying ¹H decoupling during acquisition would saturate the ¹H signals and prevent them from being detected. To acquire pure shift ¹H NMR spectra two ingenious modifications have been developed to enable removal of the coupling in a 1D ¹H spectrum. This technique is known as PSYCHE (Pure Shift Yielded by CHirp Excitation)¹.

Measuring long range heteronuclear couplings

Three bond coupling constants are particularly useful for determining stereochemistry as the Karplus relationship relates them to torsion angles. Typically, however, only a qualitative analysis to define rotamers is used, as measuring the couplings accurately is not easy. Homonuclear ³J_HH couplings are normally obtained from ¹D ¹H spectra, and are fairly straightforward to measure, but heteronuclear ³J_CH couplings are more difficult to obtain. There are a variety of methods available for measuring long range heteronuclear couplings, each with their own advantages and disadvantages. Three of them, that have been implemented at the Skaggs NMR Facility, will be described below.

Sensitivity in HMBC and LR-HSQMBC experiments

Long range correlations are critical for structure elucidation. They are typically identified using HMBC experiments¹, but a relatively recent alternative is the LR-HSQMBC experiment². Recent attempts to confirm the structure of several challenging molecules in the Facility prompted an examination of the sensitivity of these two experiments to determine which is most likely to provide the crucial long range correlations.

Distinguishing chlorine and bromine by 1H-13C HSQC

Natural products often incorporate chlorine or bromine, but less rarely are both halogens found in the same molecule. When they are, the problem becomes how to distinguish them. Typically, chlorinated carbon resonances are assumed to be shifted further downfield than brominated ones. This rule of thumb was of no help to one of our users who recently isolated a compound containing both chlorine and bromine because the two halogenated carbons had very similar chemical shifts. How then could we distinguish the two halogens?

Hadamard NMR

Hadamard NMR is a method for reducing the acquisition time of two-dimensional experiments by only acquiring the rows in the 2D that contain signals. By using a Hadamard matrix, multiple selective one-dimensional spectra can by acquired simultaneously and deconvoluted post-acquisition.

Non uniform sampling

Non uniform sampling (NUS) is a method for collecting a subset of the indirect points typically acquired, thereby reducing experiment time. As little as 10% of an indirect dimension can be collected without reducing spectral quality. NUS offers significant time savings, particularly for higher dimensionality experiments.

Aliasing

Aliasing is the appearance of resonances at somewhere other than their natural chemical shift in the indirect dimension(s) of multi-dimensional spectra. Aliasing can be used to reduce the time taken to acquire spectra without sacrificing resolution or sensitivity.

Processing: linear prediction

Linear prediction is the process of extending an FID by predicting additional points from experimental data points. It is often used in the indirect dimensions of multidimensional experiments where time restrictions prevent full sampling of the decay.

Processing: zero filling

Zero filling is the process of extending an FID with extra points of zero intensity. After fourier transformation the extra points interpolate between the experimental points smoothing the spectrum and often increasing resolution.

Processing: window functions

NMR data are often manipulated after acquisition to reduce artifacts or emphasize different aspects of the spectrum. One of the ways this is achieved is by multiplying the free induction decay (FID) by "window functions" to apodise the data. A typical application of a window function is to reduce the artifacts caused by incomplete sampling of the decaying NMR signal.