Photoinduced hole hopping through tryptophans in proteins.

Hole hopping through tryptophan/tyrosine chains enables rapid unidirectional charge transport over long distances. We have elucidated structural and dynamical factors controlling hopping speed and efficiency in two modified azurin constructs that include a rhenium(I) sensitizer, Re(His)(CO)(dmp), and one or two tryptophans (W, W). Experimental kinetics investigations showed that the two closely spaced (3 to 4 Å) intervening tryptophans dramatically accelerated long-range electron transfer (ET) from Cu to the photoexcited sensitizer. In our theoretical work, we found that time-dependent density-functional theory (TDDFT) quantum mechanics/molecular mechanics/molecular dynamics (QM/MM/MD) trajectories of low-lying triplet excited states of Re(His)(CO)(dmp)-W(-W) exhibited crossings between sensitizer-localized (*Re) and charge-separated [Re(His)(CO)(dmp)/(W or W)] (CS1 or CS2) states. Our analysis revealed that the distances, angles, and mutual orientations of ET-active cofactors fluctuate in a relatively narrow range in which the cofactors are strongly coupled, enabling adiabatic ET. Water-dominated electrostatic field fluctuations bring *Re and CS1 states to a crossing where *Re(CO)(dmp)←W ET occurs, and CS1 becomes the lowest triplet state. ET is promoted by solvation dynamics around *Re(CO)(dmp)(W); and CS1 is stabilized by Re(dmp)/W electron/hole interaction and enhanced W solvation. The second hop, W←W, is facilitated by water fluctuations near the W/W unit, taking place when the electrostatic potential at W drops well below that at W Insufficient solvation and reorganization around W make W←W ET endergonic, shifting the equilibrium toward W and decreasing the charge-separation yield. We suggest that multiscale TDDFT/MM/MD is a suitable technique to model the simultaneous evolution of photogenerated excited-state manifolds.