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

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 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 RNA 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.

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 275.6 nm,0.0266 H -> L 78% H-1 -> L+1 22% 263.6 nm,0.0298 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

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

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

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.

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

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.

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.

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

Femtosecond Pump-Probe Transient Absorption Setup Mira, Evolution, Legend 2.9 W , 800 nm, 35 fs OPA; 230-1300 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; 350-900 nm PD/PMT Lockin Amplifier Monochrometer Beam Blocker

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. PolyA AMP