Effects of Glutathione and Histidine on NO Release from a Dimeric Dinitrosyl Iron Complex (DNIC)

Pectol, D Chase; Khan, Sarosh; Elsabahy, Mahmoud; Wooley, Karen L.; Lim, Soon-Mi; Darensbourg, Marcetta Y.

doi:10.1021/acs.inorgchem.0c02196

Cited by 8 publications

(6 citation statements)

References 55 publications

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“…Further therapeutic DNICs were applied to smooth muscle cells to encourage vascular relaxation and contraction by Darensbourg and Lim. They demonstrated that thiophenolate- and thioglucose-bridged, dinuclear DNICs, [(μ-SPh) 2 Fe 2 (NO) 4 ] ( 184 ) and [μ-(SGlu) 2 Fe 2 (NO) 4 ] ( 199 ), release NO to the cytosol of smooth muscle cells with limited cytotoxity and immunotoxicity over 24 hours, without disrupting the cell’s natural processes. ,, …”

Section: Dinitrosyl Iron Complexes (Dnics)mentioning

confidence: 99%

The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity

et al. 2021

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Nitric oxide (NO) is an important signaling molecule that is involved in a wide range of physiological and pathological events in biology. Metal coordination chemistry, especially with iron, is at the heart of many biological transformations involving NO. A series of heme proteins, nitric oxide synthases (NOS), soluble guanylate cyclase (sGC), and nitrophorins, are responsible for the biosynthesis, sensing, and transport of NO. Alternatively, NO can be generated from nitrite by heme- and copper-containing nitrite reductases (NIRs). The NO-bearing small molecules such as nitrosothiols and dinitrosyl iron complexes (DNICs) can serve as an alternative vehicle for NO storage and transport. Once NO is formed, the rich reaction chemistry of NO leads to a wide variety of biological activities including reduction of NO by heme or non-heme iron-containing NO reductases and protein post-translational modifications by DNICs. Much of our understanding of the reactivity of metal sites in biology with NO and the mechanisms of these transformations has come from the elucidation of the geometric and electronic structures and chemical reactivity of synthetic model systems, in synergy with biochemical and biophysical studies on the relevant proteins themselves. This review focuses on recent advancements from studies on proteins and model complexes that not only have improved our understanding of the biological roles of NO but also have provided foundations for biomedical research and for bio-inspired catalyst design in energy science.

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Section: Dinitrosyl Iron Complexes (Dnics)mentioning

confidence: 99%

The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity

et al. 2021

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“…It has been reported that the NO release ratio is dependent on the chemical structure of the donor itself and the chemical environment . Therefore, we believe that modification of NO donor structures by various groups will affect the release amount of NO. , …”

Section: Introductionmentioning

confidence: 91%

“…31 Therefore, we believe that modification of NO donor structures by various groups will affect the release amount of NO. 32,33 In view of the above, different electron-donating and electron-withdrawing groups such as methyl, chloro, and bromo groups on the aromatic ring were selected to optimize the structure of H1. By detecting NO contents under both normoxia and hypoxia, the NO release ratio of the resulting NO donor compounds with a hypoxia-activating moiety was assayed under hypoxia.…”

Section: ■ Introductionmentioning

confidence: 99%

Discovery of Efficient Hypoxia-Targeted NO Donor Compounds to Alleviate Hypoxia Cardiac Disease

Yang,

Zhou,

Gou

2023

J. Med. Chem.

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In order to obtain efficient NO donor drugs to treat hypoxic cardiac disease, a series of hypoxia-targeted NO donor compounds were prepared and screened. Among them, a representative compound H3 was found to selectively release NO under hypoxia with a higher ratio than isosorbide dinitrate (ISDN). In vitro study indicated that H3 had a strong capability of alleviating vascular dilation and reducing myocardial hypoxic injury due to its effective regulation of vascular dilatation and myocardial injury-related proteins in H9c2 cells even at low concentrations. By intraperitoneal injection or intragastric administration, in vivo animal tests revealed that H3 possessed a potent antimyocardial hypoxic injury effect superior to ISDN. These findings suggest that H3 has a better effect on alleviating hypoxic cardiac disease than the conventional drug, owing to its hypoxia-targeted release of NO.

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“…Derived from nitrosylation of a labile iron pool (LIP) or iron–sulfur (Fe–S) clusters, a dinitrosyl iron unit (DNIU) [Fe(NO) 2 ] was identified as a natural metallocofactor for storage and transport of NO. − Inspired by the endogenous DNIU anchored in the protein-bound or low-molecular-weight form, synthetic dinitrosyl iron complexes (DNICs) were explored for controlled delivery of NO and biomedical applications to anti-aging, hypertension, tissue regeneration, diabetic/bacteria-infected wound healing, neurodegenerative diseases, and cancer therapy. − In particular, a pioneered study on the photochemistry of dinuclear DNICs [(NO) 2 Fe(μ-SR)Fe(NO) 2 ] discovered the light-responsive release of NO, whereas the utilization of UV/visible/near-infrared (NIR) light can be regulated by the side chain of bridging thiolate ligands. − Dinuclear DNICs [(NO) 2 Fe(μ-SCH 2 CH 2 OH)Fe(NO) 2 ] ( DNIC-OH ) and [(NO) 2 Fe(μ-SCH 2 CH 2 COOH)Fe(NO) 2 ] ( DNIC-COOH ) are stable under dark and anaerobic conditions. − , Upon incubation of DNIC-OH / DNIC-COOH in a neutral aqueous buffer solution under aerobic conditions, oxidation of bridging thiolate ligands into released disulfide weakens the Fe-to-NO π-back bonding interaction and induces the release of NO, which was indirectly evidenced by the colorimetric Griess reagent or fluorescence probes (Scheme S1). ,, A magnetic-responsive NO-release material (MagNORM) was reported through conjugation of [(NO) 2 Fe(μ- S -thioglycerol)Fe(NO) 2 ] ( DNIC-TG ) with Fe 3 O 4 , followed by encapsulation within thermoresponsive PLGA.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer’s Disease Cell Model

Chuang

Chou

Chen

et al. 2023

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. β-amyloid 1−42 (Aβ 1−42 ) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aβ aggregation and rescuing memory and learning deficit through the NO signaling pathway. Targeting the NO pathway might be a therapeutic option; however, NO has a limited half-life under the biological system. To address this issue, a biomimetic dinitrosyl iron complex [(NO) 2 Fe(μ-SCH 2 CH 2 COOH) 2 Fe(NO) 2 ] (DNIC-COOH) that could stably deliver NO was explored in the current study. To determine whether DNIC-COOH exerts anti-AD efficacy, DNIC-COOH was added to neuron-like cells and primary cortical neurons along with Aβ 1−42 . This study found that DNIC-COOH protected neuronal cells from Aβ-induced cytotoxicity, potentiated neuronal functions, and facilitated Aβ 1−42 degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.

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Effects of Glutathione and Histidine on NO Release from a Dimeric Dinitrosyl Iron Complex (DNIC)

Cited by 8 publications

References 55 publications

The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity

The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity

Discovery of Efficient Hypoxia-Targeted NO Donor Compounds to Alleviate Hypoxia Cardiac Disease

Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer’s Disease Cell Model

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