Hypochlorous Acid Scavenger Activity of HeteroarylNitrones. A Combined Experimental and Theoretical Study

FRIDA C. D. DIMARCO PALENCIA,[A] [; MARIO G. DIAZ,[A] ; ESTEBAN G. VEGA-HISSI,[A]*; SANDRA E. GOMEZ MEJIBA,[B, C]; DARIO C. RAMIREZ,[B, C] ; JUAN C. GARRO MARTINEZ

CHEMISTRY-A EUROPEAN JOURNAL

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2024

0947-6539

The HClO scavenging capacity of a group of heteroaryl-nitrones(HA N) that contain a substituted five-membered ring (furan orthiophene) in their structure was studied using experimentaland quantum computational methods. Experimentally, it wasfound that four HA N showed scavenging activity with IC50values ranging from 26.15 to 61.20 nM, while two HA N werefound to be inactive. To explain the HClO activity of theanalyzed HA N, we proposed and investigated a reactionmechanism based on a nucleophilic attack by the hypochlorousanion (pKa=7.46) on α-carbon of each HA N, taking intoaccount the results obtained by calculating the electrostaticpotential. For this purpose, we used the B3LYP functional of thedensity functional theory (DFT) and the basis set 6-311+G(d,p)included in the Gaussian 09 program. We calculated the rateconstants (k), the HOMO and LUMO energies, and severalreactivity indices such as the electronic chemical potential (μ),chemical hardness (η), and global electrophilicity (ω) toestablish a quantified relationship with the observed activities.The SAR analysis and the correlation between the rate constantsand the global electrophilicity with the HClO scavenging activityallow us to explain the experimental activity presented by thesix HA N analyzed