Revealing of the cation-binding sites on the surface of hemoglobin in its reaction with the NO donor, the nitrosyl iron complex {Fe2[S(CH2)2NH3]2(NO)4}SO4·2.5H2O

Interaction of Hemoglobin with Binuclearcationic Tetranitrosyl Iron Complex with Penicillamine. Cations Binding Sites

“…In [8] the authors explain why the HbNO formation reaction should "track" the NO released from NIC. We firmly established that Hb usually stabilizes the NIC and the reaction of NO release in the presence of Hb is slower than without Hb, as was found in the determination of the reaction rate of NO release from NIC using the sensor electrode [12]. We have determined that sulfur ligands, which are part of the NICs with excess electron density, contribute to the stabilization of complexes in solution [9].…”

“…In the case of the cationic NIC (II), having thiol ligands cysteamine instead of penicillamines there was significant stabilization of the complex in the presence of Hb. This was attributed to the presence of the cationic sites, negative charge centers, reversible binding (II), and that these centers were visualized [12]. The size of (I) was greater than the size of (II).…”

“…The size of (I) was greater than the size of (II). Thus, using the program PyMOL [16], we found that the size of the (I) dication is ~375 Å 3 , while the size of the (II) dication is equal to ~265 Å 3 [12].…”

“…It is consumed in the reactions of NO, known as the universal controllers necessary for functions of cellular metabolism [1] [2]. In [12], the authors observed a decrease in the processing rate for NO release for cysteamine cationic NIC (II) in the presence of Hb, which was explained by adsorption of the complex by the Hb molecule, resulting in a substantially reduced capacity of (II) to evolve NO. For (I), a structural analog of (II), the reaction scheme corresponds to a model of the given process:…”

“…As a result of allosteric binding, DPG affects Hb affinity for O 2 . Recently, we have identified the binding sites of cations in Hb [12]. It was found that a cationic NIC (Figure 1) with cysteamine ligands (II) [Fe 2 (S(CH 2 ) 2 NH 3 ) 2 (NO) 4 ]SO 4 •2.5H 2 O (CCDC 663194), was a promising anticancer NO-donor agent, apoptosis inducer in human tumor cells [13], bound with two negatively charged cavities on the Hb surface.…”