Effect of albumin on the transformation of dinitrosyl iron complexes with thiourea ligands

Abstract

Interaction and transformation of the mononuclear cationic dinitrosyl iron complex [Fe(SC(NH2)2)2(NO)2]+ (complex 1) upon binding with bovine serum albumin (BSA) have been explored using kinetic measurements, UV-Vis and fluorescence spectroscopy,...

Endogenous Conjugation of Biomimetic Dinitrosyl Iron Complex with Protein Vehicles for Oral Delivery of Nitric Oxide to Brain and Activation of Hippocampal Neurogenesis

“…Relevant to the aerobic degradation of DNIC-1 described above, the oxidation of an Fe-bound [HOCH 2 CH 2 S] − thiolate ligand in the mononuclear S = 1/2 {Fe(NO) 2 } 9 DNIC [(NO) 2 Fe(SR)(BSA)] (R = CH 2 CH 2 OH) may lead to the generation of the proposed DNIC [(NO) 2 Fe(BSA)] intermediate. 52 , 53 Presumably, the subsequent release of ∼1.4 equiv of nitric oxide from the DNIC [(NO) 2 Fe(BSA)] intermediate results in the ultimate formation of the [Fe(BSA)] adduct ( Figures 2 g and S6 ). 52 The effect of free l -cysteine on the aerobic degradation of DNIC-1 was also explored.…”

“… 52 , 53 Presumably, the subsequent release of ∼1.4 equiv of nitric oxide from the DNIC [(NO) 2 Fe(BSA)] intermediate results in the ultimate formation of the [Fe(BSA)] adduct ( Figures 2 g and S6 ). 52 The effect of free l -cysteine on the aerobic degradation of DNIC-1 was also explored. On the basis of the concentration of free thiol on Cys-34 derived from 10 mg/mL of BSA, an addition of 150 μM l -cysteine to 25 μM DNIC-1 shortens the half-life to 0.4 ± 0.1 h ( Figures 2 e,f and S7 ).…”

“…As shown in Figure b, the selective modification of the cysteine residue within the BSA by N -ethylmaleimide (NEM) inhibits the formation of this distinctive EPR signal. Considering the intrinsic binding affinity of a soft DNIU [Fe­(NO) 2 ] toward S-based ligands, consequently, the reaction of DNIC-1 and BSA is proposed to lead to the assembly of mononuclear S = 1/2 {Fe­(NO) 2 } 9 DNIC [(NO) 2 Fe­(SR)­(BSA)] (R = CH 2 CH 2 OH) via the cleavage of dinuclear {Fe­(NO) 2 } 9 -{Fe­(NO) 2 } 9 DNIC-1 by the free thiol on Cys-34 within the BSA (Figure a). , Moreover, the spin quantitation of BSA-bound DNIC determines a 50% conversion of dinuclear DNIC-1 into the protein-bound form using DNIC [PPN]­[(NO) 2 Fe­(S 5 )] as a standard (Figure S4). In the dialysis study of BSA-bound DNIC, a steady increase of the indicative UV–vis absorption bands at 309 and 362 nm for DNIC-1 in the basolateral compartment of the dialysis system explored the reversible and dynamic interconversion between low-molecular-weight DNIC-1 and BSA-bound DNIC (Figure d) .…”

“…In comparison with the anaerobic stability of BSA-bound DNIC in PBS (pH 7.4) at 37 °C, a steady decay of the UV–vis absorption bands at 384 and 565 nm under an aerobic condition reflects a half-life of 3.5 ± 0.3 h for the BSA-bound DNIC (Figures e,f and S5), which is consistent with that of 3.5 ± 0.2 h derived from the EPR experiments described above. Relevant to the aerobic degradation of DNIC-1 described above, the oxidation of an Fe-bound [HOCH 2 CH 2 S] − thiolate ligand in the mononuclear S = 1/2 {Fe­(NO) 2 } 9 DNIC [(NO) 2 Fe­(SR)­(BSA)] (R = CH 2 CH 2 OH) may lead to the generation of the proposed DNIC [(NO) 2 Fe­(BSA)] intermediate. , Presumably, the subsequent release of ∼1.4 equiv of nitric oxide from the DNIC [(NO) 2 Fe­(BSA)] intermediate results in the ultimate formation of the [Fe­(BSA)] adduct (Figures g and S6). The effect of free l -cysteine on the aerobic degradation of DNIC-1 was also explored.…”

Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications

“…In simulated gastric fluid (SGFsp, pH 1.2), a shortened half-life of 0.4 h indicates the acid-sensitive nature of DNIC-1. To mimic the systemic circulation system, the addition of serum albumin initiated the coordination of Cys-34 toward DNIC-1 leading to the partial formation of albumin-bound DNIC, which features an accelerated release of NO with a half-life of 3.5 h in phosphate-buffered saline (PBS) [34,[39][40][41][42]. Regarding the NO-release reactivity of synthetic DNICs, their capability for the elevation of intracellular NO levels, activation of the NO-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway (NO-sGC-cGMP pathway), and regulation of cGMP-dependent cell proliferation was also reported [32,34,39,43].…”