NMR in Medicine and Biology MRI- Magnetic Resonance Imaging (water) In-vivo spectroscopy (metabolites) Solid-state NMR (large structures) Solution NMR –Bioanalytical, primary structure –Three-dimensional structure –Molecular motions –Molecular interactions- binding, reactions Ligand screening (Pharma)
Nuclear Spin Nuclear spin angular momentum is a quantized property of the nucleus in each atom, which arises from the sub-atomic properties of neutrons and protons The nuclear spin angular momentum of each atom is represented by a nuclear spin quantum number (I) All nuclei with odd mass numbers have I=1/2,3/2... Nuclei with even mass numbers and an even number of protons have I=0 Nuclei with even mass numbers and an odd number of protons have I=1,2,3… Biomolecular NMR: primarily spin 1/2 nuclei ( 1 H, 13 C, 15 N, 31 P)
Nuclei With Non-Zero Spin Align in Magnetic Fields HoHo anti-parallel parallel Alignment Energy E = h H o Efficiency factor- nucleus ConstantsStrength of magnet
NMR: The Bar Magnet Analogy +-+- H o = force non-alignment2. release p ap p p
Resonance: Perturb Equilibrium HoHo h E H1H1 2. pump in energy E = h H o Efficiency factor- nucleus ConstantsStrength of magnet p ap 1. equilibrium EE p ap 3. non-equilibrium
Return to Equilibrium (Relax): Read Out Signals p ap 5. equilibrium h E 4. release energy (detect) p ap EE 3. Non-equilibrium
Magnetic Resonance Sensitivity E is small At room temp., N ~ 1:10 5 Intrinsically low sensitivity Need lots of sample E = h H o Efficiency factor- nucleus ConstantsStrength of magnet N p N ap = e - E/kT Sensitivity (S) ~ population) S ~ N = Increase sensitivity by increasing magnetic field strength
Intrinsic Sensitivity of Nuclei Nucleus Natural Relative Abundance Sensitivity 1 H2.7 x C6.7 x N -2.7 x P1.1 x
The Classical Treatment: Nuclear Spin Angular Momentum HoHo anti-parallel parallel Torque + int. motion = precession Precession around Z axis Larmor frequency ( ): E = h H o E = h = H 0 = Two spins All spins Sum Bulk Magnetization excess facing down