Concepts in Magnetic Resonance Part A最新文献

Electron paramagnetic resonance spectra of nitroxide radicals are reporters of molecular tumbling correlation times. The concepts of electron paramagnetic resonance and molecular tumbling are demonstrated by examination of spectra of the radical tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) in water:glycerol mixtures. Analysis of the spectral line shapes with the Kivelson model and computer simulation with EasySpin are discussed. Values of the tumbling correlation times obtained by the two methods are shown to be in good agreement. Comparison of the experimental tumbling correlation times with values calculated with the Stokes-Einstein model indicates a slip coefficient of 0.066, which is consistent with other reports for nitroxides in various solvents.

Alex D. Bain was an exceptional NMR spectroscopist who played an important role in the development of modern NMR methods and whose keen intellect and wonderful personal qualities endeared him to faculty and students alike who often sought him out for NMR advice. In this brief recollection, I will focus on a number of seminal contributions that Alex made that greatly influenced my research, illustrating how they changed the practice of modern NMR spectroscopy and laid the foundation for new experiments that are currently in widespread use.

An unusually large geminal coupling has been observed in a stereochemically rigid system that permits a favorable coupling alignment between the methylene protons and an adjacent carbon-carbon double bond. Such couplings have been found to depend on both the alignment of a line connecting the geminal hydrogens and the nodal plane of the adjacent double bond, and the orientation of lone-pair electrons on adjacent heteroatoms. Electron withdrawal from symmetrical bonding orbitals results in more slightly positive geminal coupling constants while that from antisymmetrical bonding orbitals produces more negative coupling constants, which has been found to be very large in certain rigid systems.

The presence of fluorine in an active pharmaceutical ingredient (API) can impart important pharmacological attributes with regards to metabolism, stability, and selectivity. As such, nearly one-third of newly approved small molecule drugs contain at least one fluorine atom. ¹⁹F is 100% naturally abundant lending to virtually unimpeded detection of fluorine-containing molecules, even in complex mixtures. Despite these promising characteristics, the thorough evaluation of a method for ¹⁹F qNMR (quantitative NMR) has been lacking. Herein we present experimental methodology and optimized parameters for uniform quantitative sampling of fluorine-containing drugs and we compare results obtained using both gravimetric and absolute concentration methods for data reduction.

Prof. David Case is based in the Department of Chemistry and Chemical Biology at Rutgers University. In this interview he speaks about force field development and validation, predictive power of MD models, combining physics-based force fields with empirical scoring functions, MD modeling of disordered proteins and RNA, synergies between MD simulations and NMR measurements, and chemical shift calculations. The video of this interview is available on the YouTube site (URL https://www.youtube.com/watch?v=bumGM1CWA7Y).

The measurement of residual dipolar couplings (RDCs) exhibited by samples prepared in suitable alignment media can help in the elucidation of macromolecular structures. For any dipolar interactions that are not averaged to zero by molecular reorientations RDCs provide information about the possible orientations of the averaged interactions to the magnetic field. As such they contain information about the permitted relative positions of different motionally averaged bond vectors. This situation is often induced using nematic liquid crystalline phases with which the macromolecule under study interacts. While a single set of RDC measurements does not produce unique solutions for the orientation of each bond, multiple independent RDC datasets can be combined to restrict each bond to two diametrically opposed orientations. Attempts to obtain such datasets have primarily focused on performing experiments with multiple alignment media that interact with the macromolecule of interest in a different way. Other work has attempted to control the orientation of the media itself relative to that of the magnetic field. The latter has been explored using pre-formed gels and might also be potentially realized using the application of different external fields during signal acquisition. This article seeks to clarify which approaches might generate independent RDC datasets and their utility in further restricting possible bond orientations using pictorial representations of simulated data.