An old but simple and efficient method to elucidate the oxidation mechanism of NAD(P)H model 1-Aryl-1,4-dihydronicotinamides by cations 2-methyl-5-nitroisoquinolium, tropylium, and xanthylium in aqueous solution.
Cations 2-methyl-5-nitroisoquinolinium (IQ+), tropylium (T+), and xanthylium (Xn+) were treated by an NAD(P)H model 1-(p-substituted phenyl)-1.4-dihydronicotinamide series (1) in buffered aqueous solution to give the corresponding reduced products by accepting hydride. Effects of the 4-substituents of 1 on the reaction rates were investigated. Hammett's linear free energy relationship analysis on the three reactions of 1 provides the reaction constants of -0.48, -2.2, and -1.4 with IQ+, T+, and Xn+ as the hydride acceptors, respectively. Comparison of the present reactions with the reaction examples whose mechanisms are well-known, such as the reaction of 1 with a one-electron oxidant Fe(CN)6(-3), shows that the active site of 1 in the oxidation with IQ+ is at the 4-position on the dihydropyridine ring but that the active site of 1 in the oxidations with T+ and Xn+ is at the 1-position, which is in agreement with the results from the Brønsted-type linear analysis and the relation studies of the logarithm of the second-order rate constants with the oxidation potentials of the hydride donors. According to the dependence of the reaction mechanism on the active site of 1, a conclusion can be made that the reaction of 1 with IQ+ proceeds by direct one-step hydride transfer mechanism, but the reactions of 1 with T+ and Xn+ would take place via multistep hydride transfer mechanism initiated by one-electron transfer.
Zhu
X Q
XQ
Department of Chemistry, Nankai University, Tianjin 300071, China. xqzhu@nankai.edu.cn
Liu
Y
Y
Zhao
B J
BJ
Cheng
J P
JP
D003508:Cycloheptanes / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D009243:NAD / Q000737:chemistry*; D009249:NADP / Q000737:chemistry*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry*; D010084:Oxidation-Reduction; D011806:Quinolinium Compounds / Q000737:chemistry*; D012996:Solutions; D013329:Structure-Activity Relationship; D013816:Thermodynamics
C430849:2-methyl-5-nitroisoquinolinium; D003508:Cycloheptanes; D006575:Heterocyclic Compounds, 3-Ring; D011806:Quinolinium Compounds; D012996:Solutions; C015145:dihydronicotinamide; C430852:tropylium; C430851:xanthylium; D009243:NAD; D009536:Niacinamide; D009249:NADP