Photoinduced hole hopping through tryptophans in proteins

Abstract

Significance Electron (hole) hopping through tryptophan residues activates protein cofactors, participates in cellular photosignaling, and protects enzymes from oxidative degradation. The energetics of excited chromophores, together with their positions relative to proximal indoles, are evolution-optimized in natural photolyases and cryptochromes. Our theoretical analysis of photoinduced hole hopping through tryptophans in rhenium-modified blue copper proteins has shed light on the roles of electronic coupling and adiabaticity, as well as electrostatic-field fluctuations and solvation dynamics in driving charge transport rapidly over long distances. The take-home message is that attention should be paid to solvation of redox-active molecules in hopping chains in the design of bioinspired light-harvesting systems and functional photocatalysts. 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 CuI 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 ReI(His)(CO)3(dmp)+–W1(–W2) exhibited crossings between sensitizer-localized (*Re) and charge-separated [ReI(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.