Bioinorganic systems responsive to the diatomic gases O₂, NO, and CO: From biological sensors to therapy

The diatomic molecules, O₂, NO and CO, have had a myriad of roles in biology. Due to this, nature has developed many sensing proteins to perceive and respond to changes in the levels of these molecules. The large majority of these proteins are metalloproteins, due to the capacity of metals to bind efficiently to those diatomic molecules. At the same time, nature developed advanced structural and electronic adjustments to fine tune these proteins for sensing, enabling them to function in diverse organisms and environmental conditions. These features are broadly discussed and focus on heme-based proteins, a superfamily of gas sensors. A brief description of heme-based sensors of O₂, NO and CO, along with a discussion on their possible role in redox sensing is presented. During the last 20 years, these systems have been more intensively studied. Some key functional and structural features have been revealed and are highlighted here. Beyond the biological sensing systems for these molecules, therapeutic interventions on those gas sensors and other biological targets can also be used. NO and CO donor molecules have become a large area of investigation that has provided compounds for many potential medical treatments, from cardiovascular disorders to bacterial infections, inflammatory issues and cancer therapy. Some newer and exciting strategies to deliver NO and CO, which provide site selectivity, and systems for efficient generation of reactive oxygen species (¹O₂) upon light control, are discussed. Overall, we bring together a fundamental understanding of gaseous regulatory metalloproteins and the design of small diatomic molecules as essential components to fuel further these major fields of interconnected studies.