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)₃(dmp)⁺, and one or two tryptophans (W₁, W₂). Experimental kinetics investigations showed that the two closely spaced (3 to 4 Å) intervening tryptophans dramatically accelerated long-range electron transfer (ET) from Cu^I 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^I(His)(CO)₃(dmp)⁺-W₁(-W₂) exhibited crossings between sensitizer-localized (*Re) and charge-separated [Re^I(His)(CO)₃(dmp^•-)/(W₁^•+ or W₂^•+)] (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)₃(dmp)⁺←W₁ ET occurs, and CS1 becomes the lowest triplet state. ET is promoted by solvation dynamics around *Re(CO)₃(dmp)⁺(W₁); and CS1 is stabilized by Re(dmp^•-)/W₁^•+ electron/hole interaction and enhanced W₁^•+ solvation. The second hop, W₁^•+←W₂, is facilitated by water fluctuations near the W₁/W₂ unit, taking place when the electrostatic potential at W₂ drops well below that at W₁^•+ Insufficient solvation and reorganization around W₂ make W₁^•+←W₂ ET endergonic, shifting the equilibrium toward W₁^•+ 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.