ShakaROESY n friends

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Shaka-ROESY n friends

• Brent Riffel Brett Shapiro
• Chem 172 May 7, 2002

Brent Riffel Brett Shapiro May 7, 2002
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The Big Picture

• Who Erythromycin Enol Ether
• What Assign NOEs between protons
• Why Elucidate 3D Structure
• How NOE Difference Spectrum GOESY New
  Shaka-ROESY

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Erythromycin Enol Ether

• Antibiotic metabolite
• From Erythromycin A
• Diarrhea, Flatulence
• Structure
• Two sugar rings
• Lactone ring
• Examine 1" proton

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Preliminary 3D Conformation

• Prior Research
• Preliminary structure from ROESY data (SYBYL)
• Current Project
• Examine 1'' proton protons in spatial proximity

1"
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ROESY and Shaka-ROESY

• ROESY
• Peak phase independent of tc
• Traps magnetization about y-axis using spin-lock
• Problems
• COSY contamination from antiphase magnetization
• TOCSY contamination when Hartmann-Hahn condition
  met
• Shaka-ROESY
• Advanced pulse sequence suppresses TOCSY
  contamination

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Shaka-ROESY
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Zoom in on Shaka-ROESY!
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Nuclear Overhauser Effect

• NOE caused by dipole-dipole relaxation
• Relevant parametersare T1 and tc
• Double quantum (2Q) zero quantum (0Q)
  transitions allowed in relaxation

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NOE Difference Experiment

• Irradiate to saturate protons magnetic
  transitions
• Baseball bat (!!!)
• System seeks equilibrium (0Q 2Q transitions)
• NOE diff. Spectrum
• irradiated MINUS control
• Negative peak corresponds to proton of interest
• Positive peaks indicate NOE
• Subtraction artifacts
• Peaks are dependent on tc

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Theoretical
Erythromycin Enol Ether
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GOESY Theory 1

• GOESY Gradient Enhanced Overhauser Spectroscopy
  
• NO subtraction artifacts
• ½ S/N ratio as NOESY, but more than com-pensates
  b/c no subtraction artifacts
• Detect NOE enhancements lt 0.1

Comparison of GOESY and NOE Difference Spectra
for Progesterone. Adapted from J. Am. Chem.
Soc., Vol. 117, No. 14, 1995.
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GOESY Theory II
GOESY Pulse Sequence 90º(x, sel)-G1-90º(x)-tm-Gm-
90º(x)-t2-180º(x)-G2-acq

• G1 and G2 adjusted to exactly defocus and refocus
  the magnetization
• Gm eliminates all but wanted
  z-magnetization
• Peaks in spectrum
• Protons selectively irradiated
• Nearby protons experiencing cross-relaxation

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GOESY and NOE diff. Compared
Proton Spectrum
GOESY Spectrum
NOE diff. Spectrum
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Zoom in on GOESY!
GOESY Spectrum (full)
Proton Spectrum (expansion)
GOESY Spectrum (expansion)
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Problems with GOESY
Original GOESY Pulse Sequence
90º(x, sel)-G1-90º(x)-tm-Gm-90º(x)-t2-180º(x)-G2-a
cq

• Can have zero-q coherence
• Caused by 2nd 90º(x) pulse
• Cannot be separated from wanted z-magnetization
• Appears in spectrum antiphase

Pulse sequence developed by the SHAKA group to
suppress antiphase contributions
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Compare to 3D Preliminary Conformation
3"OMe
4"
2"ax
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2"eq
1"
2Me