J. Phys. Chem. B 2008, 112, 3231-3239
3231
Solvation Dynamics of Hoechst 33258 in Water: An Equilibrium and Nonequilibrium Molecular Dynamics Study Kristina E. Furse, Beth A. Lindquist, and Steven A. Corcelli* Department of Chemistry and Biochemistry, UniVersity of Notre Dame, Notre Dame, Indiana 46556 ReceiVed: NoVember 21, 2007; In Final Form: January 28, 2008
Integrated within an appropriate theoretical framework, molecular dynamics (MD) simulations are a powerful tool to complement experimental studies of solvation dynamics. Together, experiment, theory, and simulation have provided substantial insight into the dynamic behavior of polar solvents. MD investigations of solvation dynamics are especially valuable when applied to the heterogeneous environments found in biological systems, where the calculated response of the environment to the electrostatic perturbation of the probe molecule can easily be decomposed by component (e.g., aqueous solvent, biomolecule, ions), greatly aiding the molecularlevel interpretation of experiments. A comprehensive equilibrium and nonequilibrium MD study of the solvation dynamics of the fluorescent dye Hoechst 33258 (H33258) in aqueous solution is presented. Many fluorescent probes employed in experimental studies of solvation dynamics in biological systems, such as the DNA minor groove binder H33258, have inherently more conformational flexibility than prototypical fused-ring chromophores. The role of solute flexibility was investigated by developing a fully flexible force-field for the H33258 molecule and by simulating its solvation response. While the timescales for the total solvation response calculated using both rigid (0.16 and 1.3 ps) and flexible (0.17 and 1.4 ps) models of the probe closely matched the experimentally measured solvation response (0.2 and 1.2 ps), there were subtle differences in the response profiles, including the presence of significant oscillations for the flexible probe. A decomposition of the total response of the flexible probe revealed that the aqueous solvent was responsible for the overall decay, while the oscillations result from fluctuations in the electrostatic terms in the solute intramolecular potential energy. A comparison of equilibrium and nonequilibrium approaches for the calculation of the solvation response confirmed that the solvation dynamics of H33258 in water is well-described by linear response theory for both rigid and flexible models of the probe.
I. Introduction Ultrafast solvation dynamics experiments employing organic dye molecules as fluorescent probes have been extremely successful in elucidating the detailed mechanisms and timescales for the response of solvents to instantaneous perturbations of charge distributions and geometry.1-3 In these experiments, an electrostatic perturbation is introduced by exciting the probe molecule from its ground to first excited state, producing a change in the solute intramolecular charge distribution. As the solvent molecules move to establish new equilibrium positions and orientations relative to the excited-state solute charge distribution, the emission spectrum shifts to longer wavelengths, reflecting the relaxation of the solute-solvent interaction energy. The solvent reorganization is typically characterized by a timedependent solvent response function, S(t) ) [ν(t) - ν(∞)]/ [ν(0) - ν(∞)], where ν(∞) is the emission frequency after the solvent has completely responded to the excited-state charge distribution. For most solvents, S(t) exhibits multiexponential behavior with a fast (
