Researchers from the Freunberger group at the Institute of Science and Technology Austria (ISTA) have unveiled pivotal insights into the redox chemistry of oxygen and reactive oxygen species (ROS). While some ROS play essential roles in cell signaling, the particularly harmful singlet oxygen damages cells and degrades batteries. For the first time, the team uncovers a way to tune it. The results, published in Nature, could have broad applications, including in energy storage processes.
While "oxidation" sounds oddly similar to "oxygen," the two words have little in common. Oxidation-reduction—or simply redox—refers to two tightly linked phenomena involving the exchange of electrons in a chemical reaction. The molecule that loses electrons gets oxidized, whereas the one that gains electrons gets reduced. As a result, substances can exist in various redox states. But the redox chemistry of oxygen, one of the most abundant elements, has not yet revealed all its secrets.
From the most reduced to the most oxidized form, the four common redox states of oxygen are called oxide, peroxide, superoxide, and molecular oxygen. Oxide is the form that exists in water, rust, and sand, while peroxide is commonly used in bleaching agents. On the other hand, superoxide is the closest state to molecular oxygen and is necessarily involved in any chemical reaction that consumes or generates it. Peroxide and superoxide have interesting chemical properties, making them so-called "reactive oxygen species," or ROS. But things get even more interesting with molecular oxygen.
The dark side of the oxygen we breathe
Usually, molecular oxygen is the relatively unreactive dioxygen that we breathe (O₂), known by chemists as "triplet oxygen." However, it can also exist as the highly reactive "singlet oxygen," a much more powerful and harmful ROS than superoxide. Apart from causing cell damage, this 'bad' oxygen is also a primary source of degradation in human-made oxygen redox systems such as batteries.
Although the 'good' triplet and 'bad' singlet oxygen have the same chemical structure and overall number of electrons, the way these electrons are distributed makes all the difference. In triplet oxygen, the two outer valence electrons are unpaired: they each occupy an orbital and spin around the oxygen atoms in the same direction. However, in singlet oxygen, the two outer valence electrons occupy the same orbital, moving in opposite directions. This leaves one electron orbital empty and very eager to snatch additional electrons from any organic molecule that crosses its path.
Professor Stefan Freunberger from the Institute of Science and Technology Austria (ISTA) underlines a fundamental problem in the redox chemistry of oxygen: "While superoxide can give rise to either singlet or triplet oxygen, we still did not know what exactly causes the 'bad' singlet oxygen to evolve and how it can be tuned."
When does oxygen take the wrong turn?
Now, a team of researchers led by Freunberger and the recent ISTA PhD graduate Soumyadip Mondal tackles the foundations of how specific ROS arise from other members of the ROS family. These molecules are relevant in a biological context principally for two roles: first, they typically cause cell damage, earning them their infamous reputation. However, these oxygen species also act as signaling agents, regulating a wide range of functions from inflammation to cell growth and all forms of cell death.
Inside cells, the mitochondria, also called the 'powerhouse of the cell,' produce superoxide. Since it is toxic to cells, the mitochondria break it down to peroxide, another ROS form that is essential for cell signaling. "We demonstrate the principle of 'superoxide disproportionation,' also known as 'superoxide dismutation,' in a laboratory setup: If two superoxide molecules 'shake hands,' one gets reduced to peroxide and the other one gets oxidized to oxygen," says Mondal. Inside mitochondria, this reaction is even accelerated by the enzyme superoxide dismutase. "But the question remains: which form of oxygen gets released—the 'good' triplet or the 'bad' singlet—and under which condition?" According to the team, the pH inside mitochondria might hold the answer.
Batteries inspired by biology
The pH inside our cells varies greatly between the compartments known as organelles. It can range from 4.7 in the acidic lysosomes—the cell's 'degradation centers'—to 8.0 inside mitochondria. This alkaline—or basic—environment is essential for the mitochondria so they produce large amounts of ATP, the 'molecular unit of currency' for intracellular energy transfer.
The team shows that the driving force for superoxide disproportionation is pH-dependent. "There is a competition between two forms of oxygen gas: if one dominates, the other slows down," says Freunberger. At a high (basic) pH, the driving force is low, and more 'good' triplet oxygen is produced. This is the scenario that plays out inside mitochondria. However, if the environment shifts to an acidic (low) pH, the reaction's driving force will increase. In this case, the levels of 'good' oxygen drop fast, and the 'bad' singlet oxygen quickly gains the upper hand. The scientists linked this behavior to the Marcus theory, which describes a reaction's initially growing speed followed by its counterintuitive slowing down beyond a specific driving force .
In non-biological applications, the team must still find defense mechanisms that will help them tune the reaction and put the 'bad' oxygen on a leash. "Biological systems know how to defend themselves from singlet oxygen. Whether we are doing basic chemistry or developing batteries, we must take inspiration from biology to keep the reaction's driving force low," says Mondal. The team can do so either by using the right combination of cations and electrolytes in the reaction solution or by developing better defense systems, such as materials that can resist or quench singlet oxygen.
Optimizing green energy processes?
While the Freunberger group specializes in materials electrochemistry and focuses on applications in energy storage devices such as rechargeable batteries, their present findings affect the very foundations of redox chemistry. The fundamental relevance of this research thus promises broad applications in pure chemistry, the life sciences, and energy storage. Beyond advancing rechargeable battery technologies, the findings may also help optimize water splitting, a technique used to produce green fuel hydrogen while releasing molecular oxygen as a byproduct. However, water splitting as a green energy source remains inefficient and often consumes more electrical energy than the generated hydrogen is worth. "How singlet oxygen formation impacts the efficiency of water splitting and potentially degrades the electrolyzer's carbon carrier remains to be investigated," says Freunberger. "With our present knowledge, we might soon be able to tame the 'bad' oxygen in various applications."
