title: On the Importance of C-H/π and C-H⋅⋅⋅H-C Interactions in the Solid State Structure of 15-Lipoxygenase Inhibitors Based on Eugenol Derivatives.
abstract: 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/π 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 π 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/π and C-H⋅⋅⋅H-C interactions in the solid state.
authors.affiliation: Department of Chemistry, Ferdowsi University of Mashhad, Mashhad 917751436 (Iran). mirzaeesh@um.ac.ir.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mirzaei
authors.affiliation: Department of Chemistry, School of Sciences, Ahvaz Branch, Islamic Azad University, Ahvaz 6134968875 (Iran).
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nikpour
authors.affiliation: Department of Chemistry, Universitat de les Illes Balears, 07122 Palma de Mallorca (Baleares) (Spain).
authors.forename: Antonio
authors.initials: A
authors.lastname: Bauzá
authors.affiliation: Department of Chemistry, Universitat de les Illes Balears, 07122 Palma de Mallorca (Baleares) (Spain). toni.frontera@uib.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Frontera
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005054:Eugenol / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; D005054:Eugenol; D001093:Arachidonate 15-Lipoxygenase
keywords: CH/π interaction; CH⋅⋅⋅hC interaction; DFT calculations; noncovalent interactions; supramolecular chemistry