Transcript Relaxation of Excess Electronic Energy and Ultrafast

Excess Energy Flow in DNA: Bench and
Computer Experiments Working in Unison
Carlos E. Crespo-Hernández
Department of Chemistry
Email: [email protected]
Ohio Supercomputer Center
Columbus, Ohio
April 4, 2008
Acknowledgement
Prof. Bern Kohler and Group Members
National Institute of Health (R01-GM64563)
Prof. Terry Gustafson and the Center for Chemical and Biophysical
Dynamics, The Ohio State University
Ohio Supercomputer Center
Case Western Reserve University
NSF-ACES Program and NSF-MRI Grant CHE0443570
Ohio Supercomputer Center Allocations
(since 2005)
Software
• Gaussian 03: 2CPUs in parallel, 10-12 hrs, ~ 150-200 RUs
• GROMACS: 4 CPUs in parallel (scaling: 99%), 150 ns trajectories @ 0.767 hrs/ns,
~ 50 RUs + ~ 100 RUs for free energy simulations: ~100 RUs
Storage Needs
• For the systems and trajectories we are currently running we use ~ 200MB/ns or ~100GB of
storage space (before compressed) + scratch space.
• Future larger model systems would necessitate larger scale simulations: 8CPus in parallel
(scaling: ~81%) at 2.4 hrs/ns.
Publications
1. Close, M. D.; Crespo-Hernández, C. E.; Gorb, L.; Leszczynski, J. J. Phys. Chem. A 2005, 109, 9279.
2. Close, M. D.; Crespo-Hernández, C. E.; Gorb, L.; Leszczynski, J. J. Phys. Chem. A 2006, 110, 7485.
3. Crespo-Hernández, C. E.; Close, M. D.; Gorb, L.; Leszczynski, J. J. Phys. Chem. B 2007, 111, 5386.
4. Crespo-Hernández, C. E.; Marai, C. N. J. AIP Conference Proceedings 2007, 963, 607.
5. Law, Y. K.; Azadi, J.; Crespo-Hernández, C. E.; Olmon, E.; Kohler, B. Biophysical J. 2008, in press.
6. Close, M. D.; Crespo-Hernández, C. E.; Gorb, L.; Leszczynski, J. J. Phys. Chem. A 2008, in press.
7. Crespo-Hernández, C. E.; Burdzinski, G.; Arce, R. J. Phys. Chem. A 2008, submitted.
Ultrafast Excited State Dynamics of Nucleic Acids
…
…
…
S1 Lifetimes for Nucleosides
DNA
4
0
6
2.5
5.0
/ ps ± 40 fs
Guo:Time
 = 460
A / 10
4
4
6
S
2
S
4
2
0
Urd:  = 230 ± 30 fs
10
8
6
4
0.0
2.5
5.0
2
/ ps ± 0.04 ps 0
Cyd:Time
 = 1.00
A / 10
2
0.0
4
RNA
4
S
4
0
A / 10
Thd:  = 540 ± 40 fs
6
Ado:  = 290 ± 40 fs
A / 10
A / 10
4
6
0.0
4
1.0
Time / ps
2
0
0.0
2.5
Time / ps
5.0
0.0
2.5
5.0
Time / ps
Pecourt, J.-M.L.; Peon, J.; Kohler, B. J. Am. Chem. Soc. 2001, 123, 10370.
Crespo-Hernández, C.E.; Cohen, B.; Hare, P.; Kohler, B. Chem. Rev., 2004, 104, 1977.
Cohen, B.; Crespo-Hernández, C.E.; Kohler, B. J. Chem. Soc., Faraday Discuss. 2004, 127, 137.
2.0
Role of Conical Intersections in the Radiationless
Decay of DNA Monomers: Cytosine
Conical intersections are a likely mechanism for the
ultrafast lifetimes of cytosine and the other DNA bases.
Pecourt, J.-M.L.; Peon, J.; Kohler, B. J. Am. Chem. Soc. 2001, 123, 10370.
Merchán, M.; Serrano-Andrés, L. J. Am. Chem. Soc., 2003, 125, 8108.
Nucleic Acid Multimers Photophysics:
The Role of Base Stacking and Base Pairing
Effect of Base Stacking Interactions
TD-DFT/B3LYP/6-311G(d,p)
L+1
L
Dinucleotides: stack ↔ unstack
Nucleotides: unstack
1.0
s
A / 10
3
0.8
ApC
AMP + CMP
0.6
263.6 nm,0.0298
H -> L+1 60%
H-1 -> L 40%
0.4
S2
S1
275.6 nm,0.0266
H -> L 78%
H-1 -> L+1 22%
S0
0.2
H
H-1
0.0
-2
0
2
4
6 8
2
4
10
Time / ps
6 8
2
100
1.2
1.0
A / 10
3
TpdA
AMP + TMP
1.0
s
A / 10
3
1.5
0.6
s
0.5
ApA
AMP
0.8
0.4
0.2
0.0
-2
0
2
4
6 8
10
Time / ps
2
4
6 8
100
0.0
-2
0
2
4
6
10
Time / ps
2
4 6
2
100
4
Electronic Coupling versus Interchromophoric Distance
TD-DFT/B3LYP/6-311G(d,p) Calculations of A-Form ApA
Crespo-Hernández, C.E.; Marai, C.N.J. AIP Conference Proceedings 2007, 963, 607.
LUMO
A-AA6
HOMO
R
AA
AMP
5.0
4.8
E= 0.2 eV
4.6
3.0
4.0
5.0
Distance / Å
S1
S2
6.0
-1
5.2
R=4Å
R=3Å
Excition Splitting / cm
Excitation Energy / eV
A-AA
R=5Å
R=6Å
3000
2500
2000
1500
1000
500
-80
-40
0
40
 P-O Torsion Angle / degrees
80
Ade
Reversible Redox Potentials of DNA Nucleosides
Crespo-Hernández, C.E.; Close, M. D.; Gorb, L.; Leszczynski J. Phys. Chem. B 2007, 111, 5386.
Charge Transfer Character of the Excimer/Exciplex
Tomohisa, T.; Su, C.; de la Harpe, K; Crespo-Hernández, C.E.; Kohler, B. Proc. Natl. Acad. Sci. USA 2008, accepted.
G°  E°ox - E°red  IP - EA
The decay rates of the long-lived states increase with increasing driving force
for charge recombination as expected in the Marcus inverted region.
Role of the Driving Force for Charge Separation
Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Nature 2005, 436, 1141.
Crespo-Hernández, C. E.; de la Harpe, K.; Kohler, B. J. Am. Chem. Soc. 2008, submitted.
d(AT)9•d(AT)9
A / 10
-3
0
250 nm
-5
-10
H2O
D2O
-15
-20
0
5
10
Time / ps
100
1000
d(GC)9•d(GC)9
5
d(IC)9•d(IC)9
0
buffer
D2O
-10
-15
-20
-25
3
-5
A / 10
A / 10
3
0
buffer
D2O
-4
-8
-12
20
40
60
2
100
Time / ps
3
4 5 6
1000
10
ΔG(GC) > ΔG(AT) > ΔG(IC)
20
30
40
50100
Time / ps
2
3
4 5 6
1000
Excited State Dynamics and DNA Photochemistry:
Making Connections
Singlet or triplet state?
UV
Formation time scale?
T<>T photodimers account
for ~90% of DNA Damage*
* Cadet, J.; Vigny, P. In Bioorganic Photochemistry; Morrison, H., Ed.; Wiley: New York, 1990; Vol.1, p 1.
Thymine Dimerization in DNA is an Ultrafast Reaction
Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Nature 2005, 436, 1141.
Schreier, W.J.; Schrader, T.E.; Koller, F.O.; Gilch, P.; Crespo-Hernández, C.E.; Swaminathan, V.N.; Carell,
T.; Zinth, W.; Kohler, B. Science 2007, 315, 625.
Steady State IR
fs-Time-Resolved IR
fs-Transient Absorption
570 nm
5'-TTTTTTTTTTTTTTTTTT-3'
TMP
0.25
 = 740  12 fs
s
A / 10
-3
0.50
0.00
-2
0
2
4
100
Time / ps
1000
Prediction of T<>T Yields from MD Simulations
Law, Y.K.; Azadi, J.; Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Biophysical J. 2008, in press.
Water/EtOH YieldExp.
YieldMD (x 102)
----------------------------------------------------------0%
1.6 ± 0.3
1.7
40%
1.1 ± 0.1
1.3
50%
0.7 ± 0.2
0.6
Hypothesis: ground-state conformation at the instant when dTpT absorbs light
controls the photodimer yield.
Conclusions
Our combined experimental and computational
studies have shown:
• Base stacking controls the excited state dynamics on single and double
stranded DNA, forming new long-lived singlet excited states not observed
in the monomers.
• The driving force for charge separation and charge recombination in the
DNA base stacks modulates the dynamics of the long-lived singlet state.
• The major DNA photoproduct, the thymine photodimer, is formed in less
than 1ps in thymine-thymine base stacks and the ground state conformation
controls whether the photodimer reaction takes place or not.
• Theoretical calculations have been essential for the visualization of the
molecular processes and the elucidation of specific mechanisms of
nonradiative deactivation of the excited states in DNA.
Conceptual Pump-Probe Transient Absorption Experiment
Energy
probe
Sn
6 eV
…
S1
…
…
S0
t = tn
probe delay
pump
t<0
t=0
t = t1
“initiation”
S1
pump
Sn
A
probe
4.2 eV
…
Time / fs
OD
kr
knr
0-
0 eV
S0
probe
600 nm
Delay / fs
pump
267 nm
Femtosecond Pump-Probe Transient Absorption Setup
Mira, Evolution, Legend
OPA; 230-1300 nm
2.9 W, 800 nm, 35 fs
mm BBO
Delay Stage
400 nm
Water Cell
mm BBO
Computer Controlled Wave Plate
1cm
267 nm
WLC; 350-900 nm
Prism-Compressor
Optical Chopper
Lockin Amplifier
Polarizer
1mm Flow Cell Beam Blocker
Monochrometer
PD/PMT
Ultrafast Deactivation Channel
for Thymine Dimerization
Boggio-Pasqua, M.; Groenhof, G.; Schäfer, L.V.; Grubmüller, H.;
Robb, M.A. J. Am. Chem. Soc. 2007, 129, 10996.
Temperature Dependence of the Decays of
PolyA and AMP
Crespo-Hernández, C.E.; Kohler, B. J. Phys. Chem. B 2004, 108, 11182.
Excimer State is Localized between two Stacked Bases.
0.8
T = 26 °C
T = 34 °C
T = 52 °C
PolyA
0.6
0.4
0.2
0.0
0
100
200
300
400
500
Time / ps
4
AMP
26 °C
34 °C
52 °C
A (Normalized)
s
A / 10
4
6
2
0
-2
0
2
4
6
Time / ps
8
A (Normalized)
s
A (normalized)
1.0
0
(a)
poly(A)n
(A)4
ApA
0
(b)
?
?
?
10
0
10
2
4 6
100
Time delay / ps
poly(A)n
(A)4
ApA
2
4 6
1000