The reductive deglycosylation of adriamycin in aqueous medium: a pulse radiolysis study.
The free radical (II) produced by one-electron reduction of adriamycin (I) exists in aqueous solution at pH 7.0 in equilibrium with the parent and the two-electron reduced form (III). Over some hundreds of milliseconds deglycosylation takes place yielding an aglycone (IV) which subsequently rearranges to form a more stable aglycone, 7-deoxyadriamycinone (V). The changes in the optical absorption spectrum accompanying these processes are reported. The rate constant for III----IV is 1.1 s-1 and for IV----V is 1.5 x 10(-2) s-1. At pH 4.0 the two electron reduced form of adriamycin exists predominantly in a different tautomeric form (VII). It is suggested that this deglycosylates via a free radical mechanism involving the acidic form of the semiquinone free radical (VI).
Lea
J S
JS
Paterson Institute for Cancer Research, Christie Hospital & Holt Radium Institute, Manchester, UK.
Rushton
F A
FA
Land
E J
EJ
Swallow
A J
AJ
D055598:Chemical Phenomena; D002621:Chemistry; D004317:Doxorubicin / Q000032:analysis* / Q000528:radiation effects; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000032:analysis; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis; D011809:Quinones / Q000032:analysis; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D005609:Free Radicals; D006873:Hydroquinones; D011809:Quinones; D004317:Doxorubicin; D005947:Glucose