Carlos E. Crespo-Hernández
Department of Chemistry
Email: carlos.crespo@case.edu
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.

Ultrafa st Excited Sta te Dynamics of Nucleic Acids
…
…
…

S
1
Lifetimes for Nucleosides
6
4
2
0
6
4
Ado:

= 290 ± 40 fs
DNA
6
4
0.0
2.5
Guo:

= 460 ± 40 fs
5.0
2
0
6
Thd:

= 540 ± 40 fs
0.0
2.5
5.0
Cyd:

= 1.00 ± 0.04 ps
10
8
6
4
2
0
4
RNA
Urd:

= 230 ± 30 fs
0.0
1.0
Time / ps
2 2
0 0
0.0
2.5
Time / ps
5.0
0.0
2.5
Time / ps
5.0
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
Nucleotides: unstack
↔ unstack
0.4
0.2
0.0
1.0
0.8
0.6
-2 0 2
ApC
AMP + CMP
4
6 8
10
Time / ps
2 4 6 8
100
2
263.6 nm, 0.0298
H -> L+1 60%
H-1 -> L 40%
S
2
S
1
S
0
H
275.6 nm, 0.0266
H -> L 78%
H-1 -> L+1 22%
H-1
1.5
1.0
0.5
0.0
-2 0
TpdA
AMP + TMP
2 4
6 8
10
Time / ps
2 4 6 8
100
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-2 0
ApA
AMP
2 4
6
10
Time / ps
2 4 6
100
2 4

R
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
A-AA
R = 3 Å
5.2
AA AMP
5.0
4.8
S
1
S
2
4.6
 E= 0.2 eV
3.0
4.0
5.0
Distance / Å
6.0
R = 4
Å
3000
2500
2000
1500
1000
500
R = 5
Å
R = 6
-80 -40 0 40

P-O Torsion Angle / degrees
80
Å
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
-5
-10
5
0
-15
-20
-25
0
-5
-10
-15
-20
0
250 nm
H
2
O
D
2
O
5 10 100
Time / ps d(GC)
9
•d(GC)
9
1000 d(IC)
9
•d(IC)
9
buffer
D2O
0
-4
-8
buffer
D2O
20 40
-12
60
100
Time / ps
2 3 4 5 6
1000
10 20 30 40 50
100
Time / ps
ΔG(GC) > ΔG(AT) > ΔG(IC)
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
0.50
0.25
fs-Transient Absorption
570 nm 5'-TTTTTTTTTTTTTTTTTT-3'
TMP
0.00
-2 0 2 4
Time / ps
100 1000
 = 740  12 fs

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 Yield
Exp.
Yield
MD
(x 10 2 )
-----------------------------------------------------------
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
6 eV
4.2 eV
0 eV probe pump k r
S n

A
S
1 k nr

OD
0-
S
0 t < 0 probe
600 nm probe
…
…
S n
S
1 pump t = 0
“initiation” t = t
1
Time / fs
…
…
S
0 t = t n probe delay pump
267 nm
Delay / fs

Femtosecond Pump-Probe Transient Absorption Setup
Mira, Evolution, Legend
2.9 W, 800 nm, 35 fs
OPA; 230-1300 nm
Optical Chopper mm BBO
400 nm
Computer Controlled Wave Plate mm BBO
267 nm
Prism-Compressor
Polarizer
1mm Flow Cell Beam Blocker
Lockin Amplifier
Delay Stage
Water Cell
1cm
WLC; 350-900 nm
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.

6
4
2
0
-2
0.4
0.2
0.0
1.0
0.8
0.6
0
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.
PolyA T = 26 °C
T = 34 °C
T = 52 °C
0
100 200 300
Time / ps
400 500
(a)
poly(A) n
(A)
4
ApA
0
AMP
2 4
Time / ps
6
26 °C
34 °C
52 °C
8 10
0
0
(b)
?
poly(A) n
?
(A)
4
?
ApA
10
2 4 6
100
Time delay / ps
2 4 6
1000