Probing oxidative stress: Small molecule fluorescent sensors of metal ions, reactive oxygen species, and thiols

Abstract

Oxidative stress is a common feature shared by many diseases, including neurodegenerative diseases. Factors that contribute to cellular oxidative stress include elevated levels of reactive oxygen species, diminished availability of detoxifying thiols, and the misregulation of metal ions (both redox-active iron and copper as well as non-redox active calcium and zinc). Deciphering how each of these components interacts to contribute to oxidative stress presents an interesting challenge. Fluorescent sensors can be powerful tools for detecting specific analytes within a complicated cellular environment. Reviewed here are several classes of small molecule fluorescent sensors designed to detect several molecular participants of oxidative stress. We focus our review on describing the design, function and application of probes to detect metal cations, reactive oxygen species, and intracellular thiol-containing compounds. In addition, we highlight the intricacies and complications that are often faced in sensor design and implementation.

Design and synthesis of a new rhodamine B-based fluorescent probe for selective detection of glutathione and its application for live cell imaging

“…[1][2][3] Among the many biologically important thiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), [4] GSH is well-known as the most important and abundant antioxidant in plants, animals, fungi, and some bacteria and archaea. [5][6] GSH plays essential roles in many biochemical processes, including preventing the damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides and heavy metals.…”

Mechanisms of Protective Effect of Ramulus Mori Polysaccharides on Renal Injury in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

“…The excessive generation of reactive oxygen species (ROS) that are produced under conditions of oxidative stress might cause disorder in the balance between oxidation and antioxidation and led to subsequent cell damage in the tissues [4,5]. Hyperglycemia promotes the generation of ROS in mesangial cells and tubular epithelial cells, and these processes accelerate the progression of diabetes and ultimately result in DN [6,7].…”

An N-Heterocyclic Amine Chelate Capable of Antioxidant Capacity and Amyloid Disaggregation

“…Moreover, many of the pathways proposed to produce ROS leading to AD pathology involve metal ions; therefore, we utilized the Cu-ascorbate redox system, Scheme 1, as a model to determine if the ligands could halt copper based redox activity under aerobic conditions. 7,9,18,22,24,25,50,51 This system is a useful model for studying the brain as high levels of oxygen and ascorbate are present, as described by Faller and coworkers, who employed this system to investigate the redox chemistry of amyloid systems with Cu. 76 Coumarin-3-carboxylic acid (CCA), which generates fluorescent 7-hydroxy-CCA in the presence of hydroxyl radicals, was used to quantify the reduction of oxygen by copper redox-cycling in the presence of ascorbate.…”

“…8,16−21 Transition metals are trace elements vital for normal biological function because they serve as structural drivers, cofactors, or reactive centers in proteins and enzymes. 22,23 Fenton chemistry is defined by the oxidation of redox active metal ions in their reduced from, such as Fe(II) or Cu(I), with H 2 O 2 to produce radicals that are known to cause DNA oxidation, disruption of mitochondrial membrane potentials, and lipid peroxidation. 7,18,24,25 Redox chemistry of these elements is tightly regulated throughout biology via regulatory and chaperone systems, so that protein modification, in conjunction with Fenton chemical reactions, producing cellular oxidative stress will be avoided.…”