The substituent effect from the perspective of local hyper-softness. An example applied on normeloxicam, meloxicam and 4-meloxicam: Non-steroidal anti-inflammatory drugs

Normeloxicam, meloxicam and 4-meloxicam were analyzed from the perspective of the conceptual density functional theory perspective to determine the substituent effect exerted by the methyl group that is located at the thiazole ring. This analysis was performed in absence and presence of water. The position of the methyl group suggests that differences that have been experimentally reported in a previous paper can be mainly attributable to electronic effects exerted by the substituent aforementioned group. Finally, the use of total electronic densities is encouraged in future calculations instead of densities of frontier molecular orbitals to obtain more accurate results. (C) 2014 Elsevier B.V. All rights reserved.