Nuclear Magnetic Resonance Applications - Advanced Analytical Chemistry - Lecture Slides, Slides of Analytical Chemistry

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Selected Applications of NMR  Structural analysis  Stereochemical and conformational analysis  Quantitative analysis  Solid-state analysis docsity.com NMR Experiments  NMR experiments fall into some basic categories: – Basic pulse methods  Single pulse  Selective pulse or selective decoupling  Solvent suppression – 2D and multi-dimensional experiments  unravel complex spectra by separation of overlapping signals, control of “mixing” between signals (to obtain more data) – Multiple resonance (heteronuclear techniques)  Are often 2D or nD sequences – Diffusion, dynamics and relaxation experiments docsity.com An Example of 1D NMR Top – 1H spectrum Middle – Selective pulse Bottom – homonuclear decoupling docsity.com Structural Analysis – 13C NMR and Editing 13C spectra of cholesteryl acetate: (a) continuous 1H decopling (b) 1H during acquisition (no NOE) (c) GASPE (APT) (d) DEPT-135 docsity.com The Gated Spin Echo Pulse Sequences  1D gated spin echo for 13C editing: a mixture of pulses and delays that take advantage of J-coupling differences between C, CH, CH2, and CH3 groups: broadband decoupling /2 relaxation delay  1/J 1/J X H broadband decoupling docsity.com An Example of 2D NMR – the COSY Experiment Correlations are observed between J- coupled protons! (Example is a sample of sucrose in D2O, analyzed with the double-quantum filtered version of COSY – “DQFCOSY”) docsity.com COSY Pulse Sequences  COSY-45 and double-quantum filtered COSY (the latter implements a “two proton” filter) docsity.com Structural Analysis: 1H –13C Correlation The 1H-13C HSQC analysis of clarithromycin: docsity.com Structural Analysis: 1H –15N Correlation The 1H-15N long- range HMQC analysis of telithromycin: docsity.com Determination of Relative S NOE difference spectr 42a a 88 ° H 4 i H r7oimH | a im Nye 4 on HY 22 4 Phase s O He 4 oy minor 2 Ap ‘io T 75 70 65 60 55 5.0 45 40 35 1H chemical shift (ppm from TMS) Determination of Absolute Stereochemistry Remember the ring current effect? J. A. Dale and H. S. Mosher, J. Am. Chem. Soc., 95, 512-519 (1973). C. E. Johnson and F. A. Bovey, J. Chem. Phys., 29, 1012 (1958). Che mical Shie lding around the Be nze ne Ring -2 0 2 4 6 8 10 12 0.0 2.0 4.0 6.0 8.0 Dis tance from Ring Cente r (A) A bs ol ut e Is ot ro pi c Sh ie ld in g (p pm ) Above Ring In Ring Plane Che mical Shie lding around the Be nze ne Ring (Expande d Vie w) -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1 4.0 5.0 6.0 7.0 8.0 Dis tance from Ring Cente r (A) A bs ol ut e Is ot ro pi c Sh ie ld in g (p pm ) Above Ring In Ring Plane shielding (opposes field) deshielding (aligned with field) docsity.com Solid-state Nuclear Magnetic Resonance  NMR in solids, like solution-state, relies on the behavior of nuclear spin energy levels in a magnetic field. However, the interactions that affect NMR spectra act differently.  In liquids, molecules reorient and diffuse quickly, leading to narrow isotropic resonances.  In solids, the fixed orientation of individual crystallites leads to a range of resonance frequencies for anisotropic interactions. E m=+1/2 m=-1/2 No field Field = B0 E=(h/2)B0 docsity.com Solid-state NMR: Magic-Angle Spinning  These can be averaged away over time by spinning at a root of the scaling factor:  The result of magic angle spinning (often combined with dipolar decoupling):   1cos3 cos 2 2   P broadening E. R. Andrew, A. Bradbury, and R. G. Eades, Nature, 183, 1802 (1959). I. J. Lowe. Phys. Rev. Lett. 2, 285 (1959).  The following anisotropic interactions are dependent on their orientation with respect to the large magnetic field (B0): – dipolar (homo- and heteronuclear) coupling – 1st-order quadrupolar coupling – anisotropic chemical shift docsity.com Cross-Polarization  Cross-polarization is an example of a double resonance experiment – Two resonances, typically two different nuclei, are excited in a single experiment.  Cross-Polarization combined with MAS (CP-MAS): – Enhancement of signal from “sparse” spins via transfer of polarization from “abundant” spins – The “Hartmann-Hahn condition” allows for efficient energy transfer between the two spins, usually via dipolar interactions – The basic CP pulse sequence for 1H to 13C experiments: 1H 13C CP CP 90 CW Decoupling E. O. Stejskal and J. D. Memory. “High Resolution NMR in the Solid State,” Oxford University Press, New York (1994). A. Pines, M. G. Gibby and J. S. Waugh. J. Chem. Phys., 59, 569 (1973). docsity.com LC-SPE-NMR for Impurity Analysis LC separation and solid-phase extraction (SPE) concentration docsity.com Magnetic Resonance Imaging • The basic idea: a linear magnetic field gradient imposes a linear spread of Larmor frequencies on a sample. Figure from S. W. Homans, A Dictionary of Concepts in NMR, Oxford, 1989. For more details, see P. G. Morris, NMR Imaging in Medicine and Biology, Oxford University Press, 1986. 00 B  Gradient 00 B  docsity.com Magnetic Resonance Force Microscopy Rugar, D.; et al. Nature 2004, 430, 329–332. R. Mukhopadhyay, Anal. Chem. 2005, 449A-452A.  A “combination” of AFM and EPR/NMR  Uses a nano-scale cantilever to detect spin motion induced by RF via in an magnetic field docsity.com