Kinetic studies on the reaction between dicyanocobinamide and hypochlorous acid.
Hypochlorous acid (HOCl) is a potent oxidant generated by myeloperoxidase (MPO), which is an abundant enzyme used for defense against microbes. We examined the potential role of HOCl in corrin ring destruction and subsequent formation of cyanogen chloride (CNCl) from dicyanocobinamide ((CN)2-Cbi). Stopped-flow analysis revealed that the reaction consists of at least three observable steps, including at least two sequential transient intermediates prior to corrin ring destruction. The first two steps were attributed to sequential replacement of the two cyanide ligands with hypochlorite, while the third step was the destruction of the corrin ring. The formation of (OCl)(CN)-Cbi and its conversion to (OCl)2-Cbi was fitted to a first order rate equation with second order rate constants of 0.002 and 0.0002 µM(-1) s(-1), respectively. The significantly lower rate of the second step compared to the first suggests that the replacement of the first cyanide molecule by hypochlorite causes an alteration in the ligand trans effects changing the affinity and/or accessibility of Co toward hypochlorite. Plots of the apparent rate constants as a function of HOCl concentration for all the three steps were linear with Y-intercepts close to zero, indicating that HOCl binds in an irreversible one-step mechanism. Collectively, these results illustrate functional differences in the corrin ring environments toward binding of diatomic ligands.
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America.
Dhiman
D
Maitra
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America; Department of Biochemistry and Genetics, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Iyad
I
Ali
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America.
Rasha M
RM
Abdulridha
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America.
Faten
F
Shaeib
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America.
Sana N
SN
Khan
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America.
Ghassan M
GM
Saed
Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States of America.
Subramaniam
S
Pennathur
Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America; Department of Biochemistry and Molecular Biology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, United States of America.
Husam M
HM
Abu-Soud
D003486:Cyanides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000737:chemistry*; D007700:Kinetics; D009570:Nitriles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*
D003486:Cyanides; D009570:Nitriles; D009942:Organometallic Compounds; C513735:dicyanocobinamide; C014430:cyanogen chloride; D006997:Hypochlorous Acid