On the Importance of CH/pi and CH⋅⋅⋅HC Interactions in the Solid State Structure of 15-Lipoxygenase Inhibitors Based on Eugenol Derivatives

Abstract

[eng] In this manuscript the X-ray structures of two potent and known inhibitors of 15-lipoxygenase, that is, 4-allyl-2-methoxyphenyl- 1-admantanecarboxylate (1) and allyl-2-methoxyphenyl- 1-cyclohexanecarboxylate (2), are reported. Their solid-state architectures show that they have a strong ability to establish C¢H/p and C¢H···H¢C interactions. For the former interaction, the adamantane or cyclohexane moieties are the C¢H donors and the electron-rich methoxyphenyl ring is the p system. For the latter, the C¢H bonds belong to the aliphatic rings of the inhibitors. Interestingly, the active site of lipoxygenase enzyme family is rich in isoleucine and leucine amino acids that participate in the binding of the unsaturated fatty acid substrate by means of multiple hydrophobic C¢H···H¢C interactions. By means of theoretical calculations, we analyze the ability of compounds 1 and 2 to establish C¢H/p and C¢H···H¢C interactions in the solid state.