Reversible dissociation and ligand-glutathione exchange reaction in binuclear cationic tetranitrosyl iron complex with penicillamine.
This paper describes a comparative study of the decomposition of two nitrosyl iron complexes (NICs) with penicillamine thiolic ligands [Fe2(SC5H11NO2)2(NO)4]SO4 ·5H2O (I) and glutathione- (GSH-) ligands [Fe2(SC10H17N3O6)2(NO)4]SO4 ·2H2O (II), which spontaneously evolve to NO in aqueous medium. NO formation was measured by a sensor electrode and by spectrophotometric methods by measuring the formation of a hemoglobin- (Hb-) NO complex. The NO evolution reaction rate from (I)  k 1 = (4.6 ± 0.1)·10(-3) s(-1) and the elimination rate constant of the penicillamine ligand k 2 = (1.8 ± 0.2)·10(-3) s(-1) at 25°C in 0.05 M phosphate buffer,  pH 7.0, was calculated using kinetic modeling based on the experimental data. Both reactions are reversible. Spectrophotometry and mass-spectrometry methods have firmly shown that the penicillamine ligand is exchanged for GS(-) during decomposition of 1.5·10(-4) M (I) in the presence of 10(-3) M GSH, with 76% yield in 24 h. As has been established, such behaviour is caused by the resistance of (II) to decomposition due to the higher affinity of iron to GSH in the complex. The discovered reaction may impede S-glutathionylation of the essential enzyme systems in the presence of (I) and is important for metabolism of NIC, connected with its antitumor activity.
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Lidia
L
Syrtsova
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Natalia
N
Sanina
A.N. Nesmeyanov Institute of Organoelement Compounds of RAS, 28 Vavilov Street, B-334, Moscow 119991, Russia.
Konstantin
K
Lyssenko
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Evgeniy
E
Kabachkov
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Boris
B
Psikha
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Natal'ja
N
Shkondina
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Olesia
O
Pokidova
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Alexander
A
Kotelnikov
Institute of Problems of Chemical Physics of the Russian Academy of Sciences, Academician Semenov Avenue Chernogolovka, Moscow Region 142432, Russia.
Sergey
S
Aldoshin