Hydrogen Bond Formation as Basis For Radical Scavenging Activity: A Structure–Activity Study of C-Methylated Dihydrochalcones from Myrica gale and Structurally Related Acetophenones

• Published in: Free radical biology & medicine Vol. 22; no. 1; pp. 307 - 311
• Main Authors: Mathiesen, Liv, Malterud, Karl E., Sund, Reidar B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1997
• Subjects: Acetophenones; Acetophenones - chemistry; Acetophenones - pharmacology; Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Bepridil - analogs & derivatives; Biphenyl Compounds; Chalcone - analogs & derivatives; Chalcone - chemistry; Chalcone - pharmacology; Chalcones; Diphenylpicrylhydrazyl; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Free Radical Scavengers - pharmacology; Free Radicals; Hydrogen Bonding; Magnetic Resonance Spectroscopy - methods; Molecular Conformation; Molecular Structure; Myrigalone B; Picrates; Plants - chemistry; Protons; Radical scavenging; Rats; Structure-Activity Relationship; Structure–activity; Acetophenones; Flavonoids; Free radicals; Myrigalone B; Structure–activity; Radical scavenging; Diphenylpicrylhydrazyl
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(96)00277-8

A naturally occurring flavonoid, myrigalone B (2′,6′-dihydroxy-4′-methoxy-3′,5′-dimethyl-dihydrochalcone) is an effective antioxidant and scavenger of the diphenylpicrylhydrazyl radical, while the closely related angoletin (2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethyl-dihydrochalcone) is inactive. From NMR spectra, it appears that myrigalone B has a time-averaged conformation in which the substituted aromatic ring is orthogonal to the carbonyl group, while angoletin is coplanar. By donating a phenolic hydrogen in radical scavenging, myrigalone B will lose its symmetrical structure and may thereby change to a coplanar conformation forming a strong intramolecular hydrogen bond between the remaining phenolic hydrogen and the carbonyl group. The energy gain entailed would then appear to be a driving force for the radical scavenging by myrigalone B. Angoletin, being coplanar, lacks this driving force. To verify this hypothesis, the conformation and radical scavenging activity of a series of phenolic acetophenones were studied. All substances that had an orthogonal conformation and could form intramolecular hydrogen bonds by loss of a phenolic hydrogen were DPPH scavengers, while compounds lacking these properties were inactive. From this, we propose that formation of intramolecular hydrogen bonds may lead to radical scavenging activity. Copyright © 1996 Elsevier Science Inc.