Activation-Deactivation of Inter-Peptide Bond in Fluoro-<i>N</i>-(2-hydroxy-5-methyl phenyl)benzamide Isomers, Induced by the Position of the Halogen Atom in the Benzene Ring
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Date
2022
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Abstract
The synthesis and XRD characterization at 295 K of three isomers, X-fluoro-N-(2-hydroxy-5-methyl phenyl) benzamide: (o-FPhB), (m-FPhB), and (p-FPhB), are presented. o-FPhB and m-FPhB show high structural affinity concerning molecular and packing structures. The planarity of the C1-C7(O1)-N1-C8 peptide bond in o-FPhB, and m-FPhB confers high stability, favoring its tendency to acquire a resonant structure in the peptide segment and in the molecule. For p-FPhB, a stereochemical gate opens, leading to the activation of N-H center dot center dot center dot center dot O interpeptide bonds, defining its supramolecular properties. Active participation of the halogen in the assembly of the structures is observed, forming intramolecular rings and molecule chains during crystal growth. The o-FPhB and m-FPhB form parallel sheets that develop hydrogen C-H center dot center dot center dot Cg, halogen C-F center dot center dot center dot Cg, or C=O center dot center dot center dot Cg interactions. Theoretical evaluations of the properties performed by the DFT/B3LYP/(6-311G(d,p) showed good agreement with the experimental values. The IR analysis reaffirms the presence of N-H, C=O, O-H, C-F, and C-H. In the UV-Vis, an increase in the energetic stability, O center dot center dot center dot H interactions, and electrostatic potential in the NH region reaffirm the disposition of p-FPhB for the formation of the N-H center dot center dot center dot O interpeptide bond. A molecular docking on the benzamides involving protein receptors showed similar behavior for all three isomers.
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crystal structure, fluorobenzamide, Hirshfeld surface, MEP, molecular docking