1. Chem 125 Lecture 63 Preliminary 4/1/08 Projected material This material is for the exclusive use of Chem 125 students at Yale and may not be copied or distributed further. It is not readily understood without reference to notes from the lecture.

2. A 90° pulse makes spinning nuclei ( 1 H, 13 C) “broadcast” a frequency that tells their local magnetic field.

3. MRI: locating protons within body using non-uniform field

4. MRI

5. How to find Crickets, if you can’t see them: Establish a temperature gradient and listen with a stopwatch.

6. X-Ray Tomography www.colorado.edu/physics/2000/tomography/final_rib_cage.html

7. MRI: find protons in body z-gradient Main Field (z) x-gradient y-gradient radio antenna (e.g. fluid H 2 O)

8. Functional MRI: locating protons whose signal strength is being fiddled with

9. BOLD Imaging http://www.csc.mrc.ac.uk/d/file/LargeFigs/Bell/fMRI.jpg Cell activity increases blood oxygen supply increases relaxation Functional MRI (fMRI) e.g. Blood Oxygen-Level Dependent (BOLD) Imaging Spatial Resolution ~1 mm Temporal Resolution 2 sec

10. NMR: locating protons within molecules using uniform field ?

11. HO-CH 2 -CH 3 http://www.wooster.edu/chemistry/is/brubaker/nmr Oscilliscope Trace (1951) The “Chemical” Shift 2.48 ppm Fractional difference in applied field 0.00000248 ! Requires very high uniformity of field

12. Dr. Lauterbur became interested in possible biological applications of nuclear magnetic resonance after reading a paper in 1971 by Raymond V. Damadian, who described how some cancerous tissues responded differently to the magnetic fields than normal tissue. Until then, most scientists placed the samples in a uniform magnetic field, and the radio signals emanated from the entire sample. Dr. Lauterbur realized that if a non-uniform magnetic field were used, then the radio signals would come from just one slice of the sample, allowing a two-dimensional image to be created. The nuclear magnetic resonance machine at SUNY was shared among the chemistry professors, and the other professors needed to perform their measurements in a uniform magnetic field. Dr. Lauterbur had to conduct his work at night, returning the machine to its original settings each morning. i.e. one particular frequency

13. Some of the Magnetic Resonance Spectrometers in Yale's Chemistry Department have put classical structure proof by chemical transformation (and even IR!) out of business. One “natural products” organic chemist turned to quantum theory, another to photography.

19. 500 MHz

21. 600 MHz

23. 800 MHz ~8 3 = 512 times as sensitive as 100 MHz (not to mention chemical shift advantage)

27. EPR (Electron Paramagnetic Resonance) (for Free Radicals with SOMOs) e magnet is 660x H + !

28. EPR (Electron Paramagnetic Resonance) 9 GHz ~3000 Gauss (0.3 Tesla)

29. NHFML - Florida State University Varian Associates New 900 MHz (21 Tesla) NMR spectrometers NHFML now has a pulsed field NMR at 45 Tesla (there is no charge for use, but you have to have a great experiment

30. HO-CH 2 -CH 3 http://www.wooster.edu/chemistry/is/brubaker/nmr Oscilliscope Trace (1951) 1 2 3 Area (integral) Which peak is which set of protons?

31. http://www.wooster.edu/chemistry/is/brubaker/nmr 2.91 1955 1) O 3 2) H 2 O 2 C-OH HO-C OO cis-caronic acid 1:11:1 Structural proof by chemical degradation (venerable) 3:13:1 ? ? O O O O O O O O

32. http://www.wooster.edu/chemistry/is/brubaker/nmr Advantage of “similarity” of protons (unlike IR where various modes have very different strengths) Higher Resolution Shows Splitting 1959

33. Ethyl Acetate Averages field inhomogeneities 1959

35. A 90° pulse makes spinning nuclei ( 1 H, 13 C) “broadcast” a frequency that tells their LOCAL magnetic field.

36. Components of Effective Magnetic Field. Inhomogeneous ~ 30,000 G for MRI CAT scan. (4 G/cm for humans, 50 G/cm for small animals) Applied Field: Homogeneous for Chemical NMR Spectroscopy (spin sample) Molecular Field: Net electron orbiting - “Chemical Shift” (Range ~12 ppm for 1 H, ~ 200 ppm for 13 C) Nearby magnetic nuclei - “Spin-Spin Splitting” (In solution J HH 0-30 Hz ; J CH 0-250 Hz) B effective B molecular (diamagnetic) B applied

37. Chemical Shift and Shielding high electron density shielded upfield high e - density low chemical shift low frequency deshielded downfield low e - density high chemical shift high frequency CH 3 C C-H ? ! ????? TMS B effective B molecular (diamagnetic) B applied N.B. The orbiting to give B is driven by B; so B  B.

38. ZERO! average over sphere average around circle  1/r 3 Electrons Orbiting Other Nuclei Diamagnetism from Orbiting Electrons B applied PPM

39. ZERO! average over sphere Electrons Orbiting Other Nuclei Unless orbiting depends on molecular orientation B applied Diamagnetic “Anisotropy” (depends on direction) NOT

40. Diamagnetic Anisotropy Benzene “Ring Current” B 0 can only drive circulation about a path to which it is perpendicular. If the ring rotates so that it is no longer perpendicular to B 0, the ring current stops.

41. Diamagnetic Anisotropy Acetylene “Ring Current” Warning! This handy picture of diamagnetic anisotropy due to ring current may well be nonsense! (Prof. Wiberg showed it to be nonsense for 13 C.) In acetylene C-H is parallel to B 0 when there is ring current (B 0 diminshed; shifted upfield). In benzene they are perpendicular (B 0 augmented; shifted downfield).

42. End of Lecture 63 April 1, 2009