X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics X-FEL Experiments on Organic and Biological Systems Karim Fahmy.
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X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
X-FEL Experiments on Organic and Biological Systems
Karim FahmyDivision of Biophysics
Institute of RadiochemistryHelmholtz-Zentrum Dresden-Rossendorf
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
X-FEL Experiments on Organic and Biological Systems
Talking about biological systems in the context of HED physics is challenging
High energies and densities do not necessarily help to reveal
the secrets of life
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
X-FEL Experiments on Organic and Biological Systems
Two fundamental processes govern organic and biological chemistry:
1) formation and breaking of chemical bonds
=> involves electron transfer reactions
2) conformational freedom / restriction
=> involves isomerization / protein folding, aggregation...
Problem-solving applications of X-FEL should address:
photo-inducedelectron transfer
metal organic systems
photo-inducedconformational transitions
in proteins
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Three systems to be discussed for X-FEL experiments
1) Uranyl photochemistry: excited state electron transfer affects redox state - light-dependent solubility changes, relevance to environmental mobility - technological applications (separation / photon-induced partitioning)
structural basis: ligand to metal charge transfer LMCT
photo-induced electron transfer metal organic systems
photo-induced conformational transitions in proteins
3) Photoreaction of rhodopsin (basis of vision and molecular model for hormone reception)
2) Dye-sensitized photovoltaics - ligt-induced injection of electrons from an organic chromophore into the conductance band of a semiconductor
structural basis: metal to ligand charge transfer MLCT
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Aqueous coordination chemistry and photochemistry of uranyl(VI) oxalate revisited: a density functional theory studySatoru Tsushima, Vinzenz Brendler and Karim Fahmy 2010, 39, 10953–10958
Photo-induced electron transfer metal organic systems1) Uranyl photochemistry
Observation: Complexes of UO22+ with organic acids decompose under light
reaction products CO2, CO, UVI -> UIV , depends on pH, stoichiometry...
Zhang et al. Radiochimica Acta (2010). Uranyl photochemistry: decarboxylation of gluconic acid
How does the coordination structuredefine the chemical reaction pathway?
hydrogen abstraction / charge transfer
Can it be predicted from first principles?
solution complexes of Uranyl oxalate
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Photo-induced electron transfer metal organic systems1) Uranyl photochemistry
Reaction coordinate predicted from DFT calculations based on spin density in the excited triplet state of UO2
2+
Suggestion:
optical pump / X-ray probe experiment in (poly)crystalline state
requires a) strong pump beam (optical transition in Uranyl is forbidden)
b) single shot probe X-ray: pumping is chemically destructive
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Photo-induced electron transfer metal organic systems2) Dye-sensitized photovoltaics
An organic dye transfers an electron into the conductance band of a semi onductor
DSP is beyond prototype and on the market
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Principle of Dye-Sensitized Solar Cells
nano-crystalline TiO2 electrode
Michael Grätzel, EPFL
Photo-induced electron transfer metal organic systems2) Dye-sensitized photovoltaics
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Optical transition has the character of a Metal-to-Ligand-Charge Transfer (MLCT), large cross-section, e-injection into TiO2 within fs-ps.
Suggestion:Structural and dynamic properties of dye to semiconductor electron transfer.Studies on selfassembled 2D arrays may profit from high intensity beams byenlarging the pumped surface
More general field for X-FEL studies: photocatalysis at liquid / solid interfaces
Photo-induced electron transfer metal organic systems2) Dye-sensitized photovoltaics
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Photo-induced conformational transitions in proteins3) Time-resolved protein conformational changes
The central goal in modern Structural Biology:resolve the 3D structure of large proteins
identify the structural basis of biological function
rational design of drugs, which enhance or inhibit function by interfering with key structural elements of their protein targets
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
1) The classical approach: crystallization and isomorphic replacement
- Crystallization difficult for proteins residing in the cell membrane
However: 50% of pharmaceuticals target membrane proteins
Limitations and challenges
low T trapping of intermediates in the crystal
Photo-induced conformational transitions in proteins3) Time-resolved protein conformational changes
2) Obtained structures are static
However: structural transitions are the basis of biological function
- dynamics not resolved, crystal contacts lock flexible domains
Bacteriorhodopsincurrently Rhodopsin
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Photo-induced conformational transitions in proteins3) Time-resolved protein conformational changes
Suggestion: Follow structural changes in rhodopsin, a photosensitive membrane protein
Primary photoreaction (200 fs)followed by slow thermally activated conformational changes
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
Photo-induced conformational transitions in proteins3) Time-resolved protein conformational changes
Rhodopsin can be prepared in a variety of states:
3D and 2D crystals, micelles, liposomes, nanodiscs
a = 44 Åb = 131 Å
Davies et al., 1996 JStrBiol
functionality in these states is well characterized
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
high energy pump and probe may allow sampling large spot sizesin lateraly extended samples
visualize photoisomerization in real-time (fs-ps) at atomic resolution
alternatively: small angle X-ray scattering may resolve helical movements
visualize large domain movements over ~100 µs
Photo-induced conformational transitions in proteins3) Time-resolved protein conformational changes
The longer time scales are more informative for pharmacology
X-FEL Workshop, Dresden-Rossendorf, Sep. 5th to 10th 2011 Karim Fahmy, Div. Biophysics
SUMMARY
There is large interest in studying biological photoreaction mechanismsat atomic resolution and in real time:
- metal organic systems in photosynthesis and photocatalysis are attractive
- proteins should be studied for which crystal structures have been solved
- fs to ps data are relevant to quantum yields (primary photoreaction)
- longer time scales are required to elucidate protein function
- rhodopsin has become a paradigm for membrane proteins and will surely find its way into time-resolved X-ray studies
- but where: at synchrotron or at X-FEL?
- many aspects have not been addressed but may become crucial: liquid sample handling, flow through systems, hydration control... a.o. efforts to maintain nativeness
THANK YOU FOR YOUR ATTENTIONnon-native fishnative olive oil
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