Electron and Charge Transfer with Copper Complexes
Copper is one of the most important redox active metals and plays a central role in many biological processes.Blue copper electron transfer proteins (or Type 1 proteins) are nature´s workhorses for electron transfer. They use copper as a one electron relay, shuttling between the cuprous and cupric oxidation states. Their Cu(II)/Cu(I) reduction potentials span a large window, which tailors these proteins to interact with a wide variety of electron transfer (ET) partners. The inner coordination sphere most directly affects the redox properties of metal ions. The tight relationship between redox potential and structure has therefore been investigated for many years. There are multiple factors governing the redox potential: effects of first coordination sphere such as geometric constraints (tetrahedral versus square planar) and ligand donor atoms but also second coordination sphere effects.The detailed interplay between inner and second sphere charge transfer mechanism is still a crucial aspect in order to understand the functionality of these redox potentials. The amount of \(\sigma\)- and/or \(\pi\)-donation of the ligands pushes more electron density on the metal ion, moving the Cu(II)/Cu(I) redox potential to lower (more negative) values. Moreover, the kinetics of ET are also heavily influenced by the structural distortion between cuprous and cupric oxidation states in order to lower the Franck-Condon barrier for ET. Two complementary and very powerful techniques to study the Frank-Condon barrier for ET are resonance Raman and XAFS spectroscopy.
In spite of the flexibility of the coordination geometry, Cu(II) is one of the most strongly coordinated divalent transition metal ions. It has the highest hydration free energy and the largest complexation free energy for aliphatic N-containing ligands among the first-row transition metal ions with the same charge. Three factors entails this strong coordination: high electron affinity, small ionic radius, and large ligand field stabilization energy.
Within the discussion about the ET properties of Type 1 centers, the high Cu-S covalency as well as the rigidity of the amino acid chains and their hydrogen networks have been regarded as most prominent influences for the effectivity of the electron transfer. However, the presence of sulphur is not necessary for efficient electron transfer as was shown by several reports about hard-donor type models for Type 1 Cu proteins. In this context, since several years studies on small-molecule conformationally invariant Cu(II/I) couples have been performed but good examples are rare.
For deeper analysis of the “hard donor influence”, Gray et al. have generated a series of hard-ligand (i.e. only N- and O-containing ligands) high-potential copper sites in variants of the cupredoxin azurin from Pseudomonas aeruginosa (Figure left, PDB code: 3FPY). Among these constructs, they unexpectedly observed cases featuring small Cu hyperfine splittings in EPR spectra together with accelerated ET activities. Since these properties are rare for copper complexes, they proposed in their initial report that they should be referred to as “Type Zero” sites in order to distinguish them from Type 1 centers. Furthermore, they demonstrated that the enhanced ET properties are associated with low reorganization λ values, being a measure of the associated reorganization energy owing to site rigidity conferred by the same hydrogen bond network found in the wild-type (WT) protein. The reorganization energy is directly related to the barrier height of electron transfer according to the Marcus theory (Figure right). They performed electronic structure calculations that show clearly that outer-sphere interactions enforce the electronic structure of Type Zero copper centers.