Density Functional Theory Study on Chemical Reactivity of Aspirin: Substituent Effect

Abstract

There is strong evidence that thrombotic and inflammatory mechanisms play a role in COVID-19 severity. COVID-19 morality may be reduced by common drugs that block these pathways, such as Aspirin. New Aspirin derivatives were suggested by functionalizing the benzene ring with acetate, amine, amide, and ribose at 2, 3, 4, and 5 positions. Through density functional theory (DFT) B3LYP / (6–31G), their energetic characteristics and chemical reactivity were estimated. The band gap of Aspirin is 0.199 eV, while 3-acetate Aspirin, 3-amine Aspirin, 4-amide Aspirin, and 5-ribose Aspirin have the least band gap equal to 0.187, 0.144, 0.177, and 0.162 eV, respectively. Electronegativity (χ), chemical potential (µ), hardness (η), electrophilicity index (ω), ionization potential (I), and electron affinity (A) of Aspirin are -0.166, 0.166, 0.098, -0.14, 0.265, and 0.068 eV, while for 3-amine Aspirin they are -0.130, 0.130, 0.072, -0.117, 0.202, and 0.058, respectively. On the other hand, the energy barriers of Aspirin and 3-amine Aspirin reactions with Serine are -39.286 and -152.559 Hartree, respectively. These results indicate that 3-amine Aspirin is more active than Aspirin. However, these results open the way for the development of new effective drugs for anti-inflammatory and cardiovascular diseases.

Keywords

• Aspirin, Chemical reactivity, DFT, Global index, Serine.