HYDROGEN-BOND FORMATION AS BASIS FOR RADICAL SCAVENGING ACTIVITY - A STRUCTURE-ACTIVITY STUDY OF C-METHYLATED DIHYDROCHALCONES FROM MYRICA-GALE AND STRUCTURALLY RELATED ACETOPHENONES

A naturally occurring flavonoid, myrigalone B hydroxy-4'-methoxy-3',5' -dimethyl-dihydrochalcone) is an effective antioxidant and scavenger o f the diphenylpicrylhydrazyl radical, while the closely related angole tin hydroxy-6'-methoxy-3',5'-dimethyl-dihydrochalcone) is inactive. Fr om NMR spectra, it appears that myrigalone B has a time-averaged confo rmation in which the substituted aromatic ring is orthogonal to the ca rbonyl group, while angoletin is coplanar. By donating a phenolic hydr ogen in radical scavenging, myrigalone B will lose its symmetrical str ucture and may thereby change to a coplanar conformation forming a str ong intramolecular hydrogen bond between the remaining phenolic hydrog en and the carbonyl group. The energy gain entailed would then appear to be a driving force for the radical scavenging by myrigalone B. Ango letin, being coplanar, lacks this driving force. To verify this hypoth esis, the conformation and radical scavenging activity of a series of phenolic acetophenones were studied. All substances that had an orthog onal 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 o f intramolecular hydrogen bonds may lead to radical scavenging activit y. Copyright (C) 1996 Elsevier Science Inc.