New Advances in Fast Methods of 2D NMR Experiments

Abstract

Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, quantification, and structural elucidation, it suffers from inherently low sensitivity limitations. This chapter focuses on recently reported methods that enable quick acquisition of NMR spectra, as well as new methods of faster, efficient, and informative two-dimensional (2D) NMR methods. Fast and efficient data acquisition has risen in response to an increasing need to investigate chemical and biological processes in real time. Several new techniques have been successfully introduced. One example of this is band-selective optimized-flip-angle shorttransient (SOFAST) NMR, which has opened the door to studying the kinetics of biological processes such as the phosphorylation of proteins. The fast recording of NMR spectra allows researchers to investigate time sensitive molecules that have limited stability under experimental conditions. The increasing awareness that molecular structures are dynamic, rather than static, has pushed some researchers to find alternatives to standard, time-consuming methods of 15 N relaxation observables acquisition.Keywords: NMR, 2D NMR, ultrafast data processing, SOFAST, relaxation 15 N, 29 Si, 30 Al, 31 P to 235 U). As the resonating frequency is unique for each type of nuclei, one can envision an NMR for each nucleus as a separate spectroscopy such as 1 H NMR spectroscopy, 13 C NMR spectroscopy, 235 U NMR spectroscopy (Figure 1), etc. More importantly, NMR has the ability to evaluate information about the environment of each atom and their neighbor's nuclei (both through space and through bond), allowing researchers to differentiate the unique magnetic environments of the same nuclei in different positions of a single molecule. Thus, NMR spectroscopy is extensively used for the identification and in the structural elucidation in a wide Nuclear Magnetic Resonance 2 range of applications in gas [2,3], liquid [4][5][6][7][8][9][10][11][12][13][14][15][16], and solid-state samples [17][18][19][20][21][22][23][24][25][26][27][28]. Nowadays, NMR spectroscopy is one of the most important analytical tools that has been used in several fields. These fields include structural biology [29][30][31][32][33][34][35][36][37][38], organic chemistry [39][40][41][42][43][44][45][46][47][48][49][50][51][52], polymer characterization [40,46,[53][54][55][56][57][58][59][60][61][62][63][64], inorganic chemistry [65][66][67][68][69][70][71][72][73][74][75], and physics [76][77][78][79][80][81][82][83].Despite its significant advantages, NMR suffers from some limitations, of which the relatively low sensitivity seems to be the most severe. An NMR sample can be treated as a collection of many nuclear spins of magnetically active nuclei that act as small bar magnets. These nuclear spins have two possible orientations with different energy levels that adapt when placed within the strong magnetic field. The number of nuclear spins occupying each energy level is determined by the Boltzmann distribution equation: N ...

NMR as a “Gold Standard” Method in Drug Design and Discovery

“…From another perspective, one can further optimize the process of obtaining spectra by using different methods of measurements. One of these, called SOFAST, helps to reduce the delay between scans resulting in lowering acquisition time for 2D experiments such as HMQC utilizing 1 H, 15 N or 1 H, 13 C [ 117 , 446 , 447 ]. The basic principle of this method is to use selective 1 H pulses that will excite only a small portion of the available nuclei pool, while the unperturbed spins provide a magnetization “heat sink” thus improving the spin-lattice relaxation (T 1 ) rate via dipolar interactions [ 446 ].…”

“…The basic principle of this method is to use selective 1 H pulses that will excite only a small portion of the available nuclei pool, while the unperturbed spins provide a magnetization “heat sink” thus improving the spin-lattice relaxation (T 1 ) rate via dipolar interactions [ 446 ]. These methods can be highly efficient when studying drug binding and molecular interactions [ 117 ].…”

“…Another method, called ultrafast 2D NMR, enables obtaining a 2D spectra within a single scan but with the associated cost of reduced sensitivity [ 117 , 448 ]. The principle of this method is to divide the sample into n number of fractions, and apply the appropriate incremental aspect to each fraction, while recording them all simultaneously within the one scan [ 448 ].…”

“…Lastly, a method termed non-uniform sampling (NUS) may provide an advantage by reducing the total time for measurement while maintaining the same resolution of spectra [ 117 ]. NUS effectively skips over parts of the total dataset, collecting only around 20 to 30% of the total.…”

“…Currently, novel approaches such as “smart isotope labeling” have been developed [ 114 ]. Also, the SOFAST (Band-Selective Optimized Flip Angle Short Transient) technique can help but results in substantial hardware considerations/drawbacks and often increased concentrations, and/or dramatically longer experiments are still required [ 115 , 116 , 117 ].…”