A DFT study for paracetamol and 3,5-disubstituted analogues

Abstract

Quantum chemistry calculations at the B3LYP theory level, together with the 6-31G* basis set were employed to obtain energy ( E), ionization potential (IP), bond dissociation energies (BDE), and spin-density distribution for paracetamol (PAR) and 3,5-disubstituted analogues of PAR. Calculations of spin densities were performed for radical formed by hydrogen abstraction from the phenolic hydroxyl group. The unpaired electron remains is localized on the O 7 phenolic oxygen (31–40%), C 3 and C 5 carbon atoms at the ortho (17–27 and 21–27%) and C 1 carbon atom at the para (25–33%) positions. The correlation between analgesic activity, cytotoxicity, and electronic properties was obtained by using correlation matrix. The IP, and BDE O–H are significant related with the in vitro inhibition of cyclooxygenase, while BDE O–H, BDE N–H and IP are significant related with the cytotoxicity (LDH).