Reactions of OH-radicals with procarbazine. A pulse radiolysis and computer simulation study
Delipetar-Grudl, A.; Solar, S.; Getoff, N.
Anticancer Research 26(1a): 405-410
2006
ISSN/ISBN: 0250-7005 PMID: 16475725 Document Number: 596752
Pulse radiolysis was applied to study the reactivity of (OH)-O-center dot radicals with procarbazine (PC), a cytostatic agent widely used in radiation- and chemotherapy. An overall rate constant of k((OH)-O-center dot+PC)=3.7x10(9) l.mol(-1).s(-1) was determined. The thereby formed transients had a strong absorption at 350 run, epsilon(350)=4.46x10(3) l.mol(-1).cm(-1), and a weak absorption band around 530 nm. Computer simulation studies to elucidate the most probable sites of (OH)-O-center dot attack on the PC molecule showed that (OH)-O-center dot radical addition to the aromatic ring had the highest probability. These transients decayed by a first order reaction, k=1.75x10(3) s(-1), whereby species having a maximum absorption at 300 nm and broad shoulder at 340-380 nm were formed. Similar absorptions were observed after gamma radiolysis of PC A reaction mechanism is suggested. For the reaction of H-atoms with PC, a rate constant k(H-center dot+PC)=6.4x10(8) l.mol(-1).s(-1) was determined.