Improving the Resolution of Quantitative NMR

Quantitation is a core challenge in chemical analysis, with particular importance in pharmaceutical research, development and quality control. NMR is unique in combining chemical specificity and resolving power with a fundamentally quantitative character: the signal intensities measured are, over a very wide dynamic range, directly proportional to the numbers of spins involved. However, in mixture analysis NMR is rarely used to its full potential. This is primarily because the methods that give the best quantitation (notably pulse-acquire) have the poorest resolution, and the methods (e.g. multidimensional NMR, pure shift NMR) that have the best resolution give relatively poor quantitation because signal is lost, through a variety of different mechanisms. This project seeks to extend the fully quantitative character of pulse-acquire methods to a much wider range of NMR techniques, giving a step function improvement in the quantitative performance of NMR methods in the most challenging analytical problems.

The student will investigate novel experimental NMR and data analysis methods for correcting the effects of signal loss in multiple pulse NMR experiments. Signal is lost through spin relaxation, through diffusion and convection in experiments using pulsed field gradients, through instrumental limitations including finite radiofrequency pulse power and variations in magnetic field gradient and radiofrequency field amplitude across a sample, and through spin physics complications such as strong coupling. We will focus initially on "pure shift" NMR methods, because these offer the highest resolving power of any current NMR techniques, but the new advances created will be applicable across the full range of multiple pulse NMR.

If successful, this research will find wide application in academic and industrial chemistry.