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

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 BDEO-H are significant related with the in vitro inhibition of cyclooxygenase, while BDEO - H, BDEN - H and IP are significant related with the cytotoxicity (LDH). (C) 2004 Elsevier B.V. All rights reserved.