A new insight into how nature operates a number of basic processes is guiding researchers in the design of proteins prepared as needed for applications such as artificial photosynthetic centers, long-distance electron transport, and catalysts for fuel cells for energy conversion.
From iron rusting, through forest fires to the beating of the human heart, redox reactions, in which electrons are transferred from one atom to another, are at the core of many chemical and biological processes. Each process requires a unique redox potential, in the same way that different electronic devices require their own unique batteries.
The manner in which nature adjusts these potentials throughout a wide variety of systems while only slightly changing the electronic properties or efficiency of the proteins still remains a mystery.
Now, a research team led by chemistry professor Yi Lu from the University of Illinois, has uncovered one of nature's secrets and begun harnessing it for its utilitarian needs. The research findings appear in an article published in the scientific journal Nature.
"We were able to show that two important interactions - hydrophobicity (the tendency to repel water) and hydrogen bonds - are able to adjust the redox potential in a certain family of copper-containing proteins, called "cupredoxins", explains the lead researcher. "We were able to extend the range, both above and below what was previously known in nature."
The research team also showed that the effects of the hydrophobicity and the hydrogen bonds are cumulative, thus enabling additional control and expanding the range of redox potentials (short for the term oxidation-reduction) beyond what nature itself offers.
In the past, in order to exploit a wide range of potentials, scientists were required to use several different redox factors in the coupling. This fact made the ability to adjust the reduction potentials without changing other properties difficult, if possible at all.
In addition, water-soluble and stable redox factors are rare, explains the researcher, and those available have a limited potential range. "As a result, there is a huge demand for water-soluble and efficient redox materials with a wide potential range for research in the fields of biochemistry or environmentally friendly aquatic environments," the researcher notes.
In order to crack nature's secrets, the scientists examined the behavior of the copper-containing protein azurin from the cuprodoxin family. These are copper-containing redox proteins that play an essential role in many important processes, including photosynthesis and cellular signaling. These proteins have a single redox center, whose potential can be adjusted without damaging their structure and electronic properties.
The researchers found that the two interactions - hydrophobicity and hydrogen bonds - can selectively increase or decrease the oxidation potential of azurin. The interactions occur not only in the main, innermost core of the protein, but also in a secondary layer surrounding the core.
Increasing the hydrophobicity of the secondary layer can greatly increase the oxidation potential, the researchers report. The more water-repellent (hydrophobic) this secondary shell is, the more the overall charge on the copper ion becomes unstable and the potential increases.
The effects of the hydrogen bonds are weaker than the effects of the hydrophobic interaction, says the lead researcher. Hydrogen bonds can both increase and decrease the electron density around the group that binds to the copper ion in the protein, thus making it easier or harder to redox, while slightly changing the redox potential.
"This is nature's secret," says the researcher. "By adjusting the hydrophobicity and the hydrogen bonds, it is possible to increase or decrease the oxidation potential, without changing the electronic properties of the protein and without impairing its efficiency." The result is a pre-designed reduction factor that can have a potential higher, lower or in between these values.
"This unprecedented level of control over electron transfer proteins was achieved by precise mapping of the main interactions," explains the researcher, "this approach can also be applied to other interesting cycling proteins."
