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 (2',6' -dihydroxy-4'-methoxy-3',5'-dimethyl-dihydrochal-cone) 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.
Mathiesen
L
L
Department of Pharmacology, School of Pharmacy, University of Oslo, Norway.
Malterud
K E
KE
Sund
R B
RB
D000098:Acetophenones / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D015764:Bepridil / Q000031:analogs & derivatives*; D001713:Biphenyl Compounds; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D015394:Molecular Structure; D010851:Picrates; D010944:Plants / Q000737:chemistry*; D011522:Protons; D051381:Rats; D013329:Structure-Activity Relationship
D000098:Acetophenones; D000975:Antioxidants; D001713:Biphenyl Compounds; D047188:Chalcones; D005419:Flavonoids; D016166:Free Radical Scavengers; D005609:Free Radicals; D010851:Picrates; D011522:Protons; C100377:myrigalone B; D002599:Chalcone; D015764:Bepridil; C105002:angoletin; C004931:1,1-diphenyl-2-picrylhydrazyl