3H: a new probe for High Resolution Solid State NMR. . . ANR MASTRIT Blanche 2005-2009
T. Charpentier CEA - IRAMIS/SIS2M/LSDRM
January 17, 2010
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
Further readings . . . JACS comm. in press.
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
Solid State NMR and distance Measurements Providing restraints for biomolecules conformation studies
Why Solid State NMR?
Low aqueous solubility Systems prone to aggregation Amorphous systems
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
Need for long distance measurements. Taxol - Tubulin interaction
Taxol T. Charpentier 3
H MAS NMR
Tubulin CEA - IRAMIS/SIS2M/LSDRM
Principles of NMR distance Measurements The Dipolar Magnetic Interaction
State of the Art
13
C,15 N: low γ ⇒ Low Sensitivity, High Resolution ⇒ Max distance 5 − 6˚ A 1
H: High γ, ⇒ High Sensitivity ⇒ Poor Resolution, Multiple couplings ⇒ 1 H / 2 H dilution required
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
Principles of NMR distance Measurements Recoupling the dipolar interaction under MAS
MAS
R
HDij (t)dt ∝
R
× RD (Ωij (t)) × Tij dt = 0
=0
MAS + rotor synchronized spin rotation (RF)
R T. Charpentier 3
H MAS NMR
HDij (t)dt ∝
R
× RD (Ωij (t)) × Tij (t)dt 6= 0
6= 0
CEA - IRAMIS/SIS2M/LSDRM
Application of
T. Charpentier 3
H MAS NMR
13
C-13 C
α-helix vs β-strand
CEA - IRAMIS/SIS2M/LSDRM
Introducing a new nucleus in High Resolution Solid State NMR 3 H:
the highest gyromagnetic ratio (γ) High sensitivity and no (probe) backgroung Very low 3 H/1 H dilution Well isolated spin pair High resolution
Higher 3 H-3 H (or 3 H-X) dipolar interaction ⇒ Longer distances can be measured Estimated highest distance dTT ≈ 15˚ A T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
Spinning a radioactive powder sample Probe Sealings and Exhaust gas containment system
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H MAS NMR at work
≈ 1018 spins in one scan.
T. Charpentier 3
H MAS NMR
3
H: (very) long T1 !
CEA - IRAMIS/SIS2M/LSDRM
3H CPMAS NMR at work Taking advantage of 3 H / 1 H dilution . . .
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement Choice of the pulse sequence
Why HORROR? Aim: recoupling the weak 3 H-3 H dipolar interactions while decoupling the strong 3 H-1 H interactions. High 1 H RF field for efficient 3 H-1 H decoupling. HORROR, Nielsen et al., J. Chem. Phys. 101, 1994 (b) Novel implementation Constant Time HORROR
T. Charpentier 3
H MAS NMR
Low 3 H RF field to avoid 3 H-1 H CP match
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement The first result !
R S(t) = A d∆ g (∆) S(t; dTT , ∆) + B exp (−t/T1ρ )
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement . . . . . . at work
6˚ A
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement . . . . . . at work
9.4 ˚ A
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement Constant Time HORROR
HORROR, Nielsen et al., J. Chem. Phys. 101, 1994 (b) Novel implementation Constant Time HORROR
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement Constant Time HORROR
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurement . . . Constant Time Approach
13.8˚ A
R S(t) = A d∆ g (∆) S(t; dTT , ∆) + B T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H-3H distance Measurements Experiment vs Theory
3
H-3 H distances (˚ A)
1
2
3
4
Predicted
4.3
6.0
9.4
13.8
Measured
4.35 (0.02)
5.90 (0.1)
9.3 (0.2)
14.4 (1.8)
3
3
Predicted (DFT-PWSCF) vs measured H- H distances.
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
3H MAS NMR Perspectives . . .
3H
( 1 H ) Chemical Shift Anistropy
3 H-X (31 P, 13 C)
distance (and geometry) measurements
Multidimensional 3 H-1 H-X spectroscopy
T. Charpentier 3
H MAS NMR
CEA - IRAMIS/SIS2M/LSDRM
Need for long distance measurements. Taxol - Tubulin interaction
15 mars 2014 - En réalité , dès que la fumée est refoulée du plafond , tout devient rapidement noir. Le danger des fumées. ICOMIX. ' C:]CHAUDE. | OPAQUE ...
Nuclei observable by NMR. Page 5. Why some nuclei have no spin ? The proton is .... Ex: D x derivative operator. Ex: 1 unity operator 1f(x) = f(x). Commutation.
framework for the design of permanent magnets for portable NMR and MRI ... the light of applications of solid-state NMR in metabolomics and cell imaging.
Structure determination from NMR data is an non-linear inverse problem: Dihedral ... Protein dynamics leads to a non-linear averaging of NMR observables ...
NMR dipolar couplings provide a highly detailed description of conformational .... P()=. 1. 2. G( )e i d. +. J()=. 1. 2 c( )e i d. +. How can we describe of these fluctuating Local Fields? ..... No direct information about slower internal motion? Ï
Nuclear magnetic resonance (NMR) is exquisitely sensitive to protein ... In particular spin relaxation measurements provide precise information about local ...
DMCA. Copyrighted Work that you can Claim. Regional uptake of 3H-melatonin from blood or cerebrospinal fluid by rat brain. MELATONIN (5-methoxy N-acetyltryptamine) is synthesized in the pineal glands of mammals through the action of the enzyme hydrox
backbone geometries in fibrous proteins [4] or the determination of ...... 2-13C-glycerol, labels are selectively accumulated in the side chains and C a positions ...
are interesting because they mimic natural DNA lesions, while others have possible medical applications in anti-sense therapy or for RNA interference. Finally ...
Special feeding unit, specially designed for this machine and covering the whole work table. Two rollers, coated in white rubber, assu- re a perfect feeding of the ...
NMR Relaxation .... can be the lattice, the vibration-rotation spectrum of the molecules or the ... extent of proton signal is about 20ppm and the separation of multiplets is ... In MRI, the problem is different if we exclude the MRSI approach, we do
proteins. Our goal now is to gather as many data as possible (such as relaxation data, SAXS,. EPRâ¦) to be able to study completely those proteins. References.
Mar 9, 2008 - Selection of residues to be taken into account for determination of D or .... are not necessary (and can be left out) if no analysis of internal mobility .... If in doubt, ask a solid state nmr spectroscopist why she/he doesn`t assume .
