1. Carlos E. Crespo-Hernández
Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison
Carlos E. Crespo-Hernández
Department of Chemistry
Ohio Supercomputer Center
Columbus, Ohio
April 4, 2008

2. Ohio Supercomputer Center Case Western Reserve University
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 CHE

3. Ohio Supercomputer Center Allocations
(since 2005)
Software
Gaussian 03: 2CPUs in parallel, hrs, ~ RUs
GROMACS: 4 CPUs in parallel (scaling: 99%), 150 ns 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.

4. Ultrafast Excited State Dynamics of Nucleic Acids… …

5. S1 Lifetimes for Nucleosides
DNA
RNA
Pecourt, J.-M.L.; Peon, J.; Kohler, B. J. Am. Chem. Soc. 2001, 123,
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.

6. 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,
Merchán, M.; Serrano-Andrés, L. J. Am. Chem. Soc., 2003, 125, 8108.

7. Nucleic Acid Multimers Photophysics:
The Role of Base Stacking and Base Pairing

8. Effect of Base Stacking Interactions
275.6 nm, H -> L 78%
H-1 -> L+1 22%
263.6 nm, H -> L+1 60%
H-1 -> L 40% S0 S1 S2 H L
L+1
H-1
TD-DFT/B3LYP/6-311G(d,p)
Dinucleotides: stack ↔ unstack
Nucleotides: unstack

9. 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.
Ade
A-AA
R = 3 Å
R = 4 Å
R = 5 Å
R = 6 Å
HOMO
A-AA6
LUMO R
AA AMP
E= 0.2 eV

10. Reversible Redox Potentials of DNA Nucleosides
Crespo-Hernández, C.E.; Close, M. D.; Gorb, L.; Leszczynski J. Phys. Chem. B 2007, 111, 5386.

11. 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.

12. 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
d(GC)9•d(GC)9
d(IC)9•d(IC)9
ΔG(GC) > ΔG(AT) > ΔG(IC)

13. Excited State Dynamics and DNA Photochemistry: Making Connections
T<>T photodimers account
for ~90% of DNA Damage* UV
Singlet or triplet state?
Formation time scale?
* Cadet, J.; Vigny, P. In Bioorganic Photochemistry; Morrison, H., Ed.; Wiley: New York, 1990; Vol.1, p 1.

14. 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
Time / ps
 = 740  12 fs

15. 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% ±
40% ±
50% ±
Hypothesis: ground-state conformation at the instant when dTpT absorbs light controls the photodimer yield.

16. Our combined experimental and computational studies have shown:
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.

18. Conceptual Pump-Probe Transient Absorption Experiment
Time / fs A Sn S1 S0
t < 0
t = 0
t = t1
t = tn …
“initiation”
pump
probe
probe delay S0 S1 kr
knr Sn
Energy
4.2 eV
0 eV
6 eV
probe
pump
DOD 0-
probe 600 nm
pump 267 nm
Delay / fs

19. Femtosecond Pump-Probe Transient Absorption Setup
Mira, Evolution, Legend
2.9 W
, 800 nm, 35 fs
OPA; nm
mm BBO
Delay Stage
400 nm
1mm F l o w C el
267 nm
mm BBO
Prism-Compressor
Computer Controlled Wave Plate
Optical Chopper
Polarizer
1cm
Water Cell
WLC; nm
PD/PMT
Lockin Amplifier
Monochrometer
Beam Blocker

20. 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,

21. Temperature Dependence of the Decays of PolyA and AMP
Crespo-Hernández, C.E.; Kohler, B. J. Phys. Chem. B 2004, 108,
Excimer State is Localized between two Stacked Bases.
PolyA
AMP