- HYPOCHLOROUS ACID SCAVENGER ACTIVITY OF NITRONES: AN EXPERIMENTAL AND THEORETICAL STUDY .

DIMARCO FCD; DÍAZ MG; VEGA-HISSI EG; ANDRADA MF; GOMEZ MEJIBA SE; RAMIREZ DC; GARRO MARTINEZ JC

SAN JUAN

Congreso; SBC; 2023

Hypochlorous acid (HOCl) is a hydrohalogenated reactive oxygen species (ROS) that is produced in living organisms, in the presence ofhydrogen peroxide (H2O2). When HOCl is produced in excessive amounts, it can oxidize the body's own biomolecules such as proteins, lipids,and nucleic acids, leading to tissue damage and the appearance of certain cardiovascular and neurodegenerative diseases in addition to otherssuch as atherosclerosis, arthritis, and cancer. A group of organic molecules called nitrones is of interest in this field because they are capableof acting as ROS scavengers. Chemically, nitrones are N-oxides of imines with a general molecular structure of the type R1R2C=N+-O- R3(where R1, R2 and R3 = an alkyl group, and R1 or R2=H). The nitrone functional group (C=N+-O-) is formed by three atoms that share four πelectrons. This specific structure is responsible for the reactivity, turning these molecules into organic compounds effective against differentoxidizing species and free radicals. The objective of this research is to determine the HOCl scavenger activity of six of nitrones, whichcontain in their structure a substituted five-membered ring (furan or thiophene), and to explain the experimental activity using computationalmethods. Experimentally, four nitrones showed HOCl scavenging activity with IC50 values ranging from 26.15 to 61.20 nM, while twonitrones were inactive. To explain their activity, a reaction mechanism based on a nucleophilic attack of the hypochlorous anion (pKa=7.46)on the α-carbon of each nitrone was proposed using DFT calculations. In addition, the rate constants (k), HOMO and LUMO energies, andvarious reactivity indices such as electronic chemical potential (μ), chemical hardness (η), and overall electrophilicity (ω) were calculated.We found that the rate constants and the global electrophilicity show a high correlation with the activity. Concurrently, we performed a SARanalysis to elucidate the influence of the substituents presented in the six nitrones.