Nuclear magnetic resonance spectroscopy: beyond molecular structure assignment

Abstract

Nuclear Magnetic Resonance (NMR) is the most powerful spectroscopic technique for detailed chemical information in solution. Fundamental parameters such as chemical shifts (d) and coupling constants (J) are the most important sources of information to achieve unequivocal molecular structure assignment. These two parameters can also be applied to determine the conformation adopted by a molecule in solution. The chemical shifts and coupling constants are dependent of electronic molecular structure and their experimental measurements can be used as a probe to evaluate small changes in electronic structure, but for these purposes, the experimental NMR parameters (d and J) must be supported by quantum chemistry calculations.NMR spectroscopy can also be applied to identify unknown components present in a sample, but the efficiency of this procedure depends on the sample. In complex biological samples, this information can unfortunately be obscured by the vast quantity of signals, so even state-of-the-art spectrometers are unable to provide sufficient resolution. Very recently, the advent of broadband homodecoupled methods (pure shift) has made available ultra-high resolution experiments that can tackle an order of magnitude more complex problems than was previously possible. In these experiments there is only a single signal (a singlet) from each type of proton, typically providing a factor 10 improvement in resolution. Even at this exquisite resolution, it can still be difficult to assign signals to different components in biological and chemical complex mixtures. Here we will employ diffusion NMR to separate the signals from different species due to their diffusion behaviour (diffusion-ordered spectroscopy, DOSY). In the most difficult cases, when compounds diffuse at the same rate (as is common for cognate species), we will manipulate the matrix in which they diffuse, analogous to what is done in chromatography, in matrix-assisted DOSY (MAD) experiments.In this application we suggest some projects such as: evaluation of conformational preferences for some small organic molecules; the influence of stereoelectronic interaction into 13C NMR chemical shift parameter for molecules containing heavy atoms, such as iodine; influence of stereoelectronic interaction on spin-spin coupling constants; evaluation of some organic reaction mechanism and application of pure shift and diffusion based NMR methods for complex mixture analysis such as pharmaceuticals and food.In this project, the deliverables will include a better understanding of important fundamental NMR parameters (´ and J), new NMR methodologies for analysis of complex sample, as well as high-level training in modern NMR, of PhD students and post docs. The latter is important to a large part of the Brazilian chemistry community. NMR is a very important tool for many chemists and well-trained NMR spectroscopists are in short supply both in laboratories at Universities and in the Industry. (AU)