Kinetic Study on the Reactivity of Azanone (HNO) toward Cyclic C-Nucleophiles.

Angelika Artelska,Monika Rola,Radosław Michalski,Michał Rostkowski,Adam Bartłomiej Sikora,Marlena Pięta,Jakub Pięta

doi:10.3390/ijms222312982

Angelika Artelska, Monika Rola + Show 5 more

Open Access

https://doi.org/10.3390/ijms222312982

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Abstract

Azanone (HNO) is an elusive electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present a comparative kinetic study of HNO reactivity toward selected cyclic C-nucleophiles under aqueous conditions at pH 7.4. We applied the competition kinetics method, which is based on the use of a fluorescein-derived boronate probe FlBA and two parallel HNO reactions: with the studied scavenger or with O2 (k = 1.8 × 104 M−1s−1). We determined the second-order rate constants of HNO reactions with 13 structurally diverse C-nucleophiles (k = 33–20,000 M−1s−1). The results show that the reactivity of HNO toward C-nucleophiles depends strongly on the structure of the scavenger. The data are supported with quantum mechanical calculations. A comprehensive discussion of the HNO reaction with C-nucleophiles is provided.

Highlights

The chemical structures of the studied C-nucleophiles are presented in Scheme 2
Our results show that the reactivity of HNO toward C-nucleophiles strongly depends on the structure of the scavenger
We studied the reactivity of cyclic C-nucleophiles containing two heteroatoms in the ring: barbituric acid (11), 1,3-dimethylbarbituric acid (10), 2-thiobarbituric acid (12)

Summary

Introduction

Over the past thirty years, several other small, reactive molecules have been identified as having similar signaling properties. This class of signaling molecules includes nitric oxide, carbon monoxide (CO), hydrogen sulfide (H2 S) and azanone (HNO, commonly known as nitroxyl) [3,4]. Research on azanone reactivity is hindered by rapid spontaneous HNO dimerization (k = 8 × 106 M−1 s−1 ) [9], resulting in the formation of hyponitrous acid, which subsequently dehydrates to nitrous oxide and water (reaction 1). Due to the rapid dimerization of HNO, in both chemical and biological research on azanone properties, it is necessary to use HNO donors that release azanone in a controlled manner [10].

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