Abstract
Some pathogens use heme-containing nitric oxide reductases (NORs) to reduce NO to N(2)O as their defense mechanism to detoxify NO and reduce nitrosative stress. This reduction is also significant in the global N cycle. Our previous experimental work showed that Fe and Co porphyrin NO complexes can couple with external NO to form N(2)O when activated by the Lewis acid BF(3). A key difference from conventional two-electron enzymatic reaction is that one electron is sufficient. However, a complete understanding of the entire reaction pathways and the more favorable reactivity for Fe remains unknown. Here, we present a quantum chemical study to provide such information. Our results confirmed Fe's higher experimental reactivity, showing advantages in all steps of the reaction pathway: easier metal oxidation for NO reduction and N-O cleavage as well as a larger size to expedite the N/O coordination mode transition. The Co system, with a similar product energy as the enzyme, shows potential for further development in catalytic NO coupling. This work also offers the first evidence that this new one-electron NO reduction is both kinetically competitive and thermodynamically more favorable than the native pathway, supporting future initiatives in optimizing NO reduction agents in biology, environment, and industry.