Electron tunneling through sensitizer wires bound to proteins

Abstract

We report a quantitative theoretical analysis of long-range electron transfer through sensitizer wires bound in the active-site channel of cytochrome P450cam. Each sensitizer wire consists of a substrate group with high binding affinity for the enzyme active site connected to a ruthenium-diimine through a bridging aliphatic or aromatic chain. Experiments have revealed a dramatic dependence of electron transfer rates on the chemical composition of both the bridging group and the substrate. Using combined molecular dynamics simulations and electronic coupling calculations, we show that electron tunneling through perfluorinated aromatic bridges is promoted by enhanced superexchange coupling through virtual reduced states. In contrast, electron flow through aliphatic bridges occurs by hole-mediated superexchange. We have found that a small number of wire conformations with strong donor-acceptor couplings can account for the observed electron tunneling rates for sensitizer wires terminated with either ethylbenzene or adamantane. In these instances, the rate is dependent not only on electronic coupling of the donor and acceptor but also on the nuclear motion of the sensitizer wire, necessitating the calculation of average rates over the course of a molecular dynamics simulation. These calculations along with related recent findings have made it possible to analyze the results of many other sensitizer-wire experiments that in turn point to new directions in our attempts to observe reactive intermediates in the catalytic cycles of P450 and other heme enzymes.

New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and 1O2 Generation

“…Excited states of Ru(II) complexes have been used in solar energy conversion, 1–5 in charge transfer reactions, 6,7 as sensors and switches, 8,9 and as potential therapeutic agents in photochemotherapy (PCT) and imaging. 10–16 Although many complexes are derived from [Ru(bpy) 3 ] 2+ (bpy = 2,2′-bipyridine) (Figure 1a), 17 these applications often have different demands.…”

Therapeutic Potential of Photochemically Active Metal Complexes based on Interaction with Enzymes

“…A more detailed analysis of the correlation between the structure of the photoactive diimine wire compounds and the electron transfer reaction to the iron center of cytochrome P450 CAM was possible using theoretical methods. This analysis revealed a dramatic dependence of electron transfer rates on the chemical structure of both the bridging group and the substrate [2].…”

“…From a point of application the cellular nucleus containing the DNA and the mitochondria containing the redox active enzymes responsible for respiration are very interesting targets which under certain conditions may be selectively reached [41,47,48]. Based on these relatively recent informations previous studies with regard to the basic understanding of electron transfer reaction in proteins between covalently bound photoactive metal complexes and metal centers of redox active enzymes become very interesting [1,2,5,[62][63][64][65][66][67][68][69][70][71][72][73][74][75][76].…”

“…Detailed studies of the interaction between rhenium(I) and ruthenium(II) complexes with metal containing proteins have been performed during the last three decades and have been summarised in several excellent reviews [1,2,5,[62][63][64][65][66][67][68][69][70][71][72][73][74][75]. Several different metallo enzymes like cytochromes, blue copper proteins and myoglobin were modified with photoactive metal complexes.…”

“…In the second process, Ru(II)* is reductively quenched by an external redox partner, followed an electron transfer to the Fe(III) center to produce an Fe(II) heme. Recent investigations suggest that especially polyfluorinated biphenyl wires still allow substrate access to the active site, which might enable a photochemically activated catalytic turn over at the heme site [77].…”