Chemiluminescence Measurement of Reactive Sulfur and Nitrogen Species

Abstract

Significance: Reactive sulfur and nitrogen species such as hydrogen sulfide (H₂S) and nitric oxide (NO^•) are ubiquitous cellular signaling molecules that play central roles in physiology and pathophysiology. A deeper understanding of these signaling pathways will offer new opportunities for therapeutic treatments and disease management. Recent Advances: Chemiluminescence methods have been fundamental in detecting and measuring biological reactive sulfur and nitrogen species, and new approaches are emerging for imaging these analytes in living intact specimens. Ozone-based and luminol-based chemiluminescence methods have been optimized for quantitative analysis of hydrogen sulfide and nitric oxide in biological samples and tissue homogenates, and caged luciferin and 1,2-dioxetanes are emerging as a versatile approach for monitoring and imaging reactive sulfur and nitrogen species in living cells and animal models. Critical Issues: This review article will cover the major chemiluminescence approaches for detecting, measuring, and imaging reactive sulfur and nitrogen species in biological systems, including a brief history of the development of the most established approaches and highlights of the opportunities provided by emerging approaches. Future Directions: Emerging chemiluminescence approaches offer new opportunities for monitoring and imaging reactive sulfur and nitrogen species in living cells, animals, and human clinical samples. Widespread adoption and translation of these approaches, however, requires an emphasis on rigorous quantitative methods, reproducibility, and effective technology transfer. Antioxid. Redox Signal. 36, 337-353.

Keywords: chemiluminescence; reactive nitrogen species; reactive sulfur species.

FIG. 1.

Reactions involved in ozone-based chemiluminescence. (A) Reactions for ozone-based chemiluminescence detection of sulfur species. (B) Mechanism for the reaction of hydrogen sulfide and ozone. (C) Reactions for ozone-based chemiluminescence detection of nitrogen species.

FIG. 2.

Reactions for the chemiluminescence detection of reactive nitrogen species with luminol.

FIG. 3.

Reactions of luminol derivatives for the detection of reactive nitrogen and sulfur species.

FIG. 4.

General mechanism for luciferin bioluminescence.

FIG. 5.

Bioluminescence probes for peroxynitrite, nitroxyl, and nitric oxide.

FIG. 6.

Bioluminescence probes for hydrogen sulfide and polysulfide species.

FIG. 7.

Bioluminescence probes for thiols.

FIG. 8.

CIEEL mechanism for 1,2-dioxetane chemiluminescence. CIEEL, chemically initiated electron exchange luminescence.

FIG. 9.

1,2-Dioxetane probes for peroxynitrite and nitroxyl.

FIG. 10.

1,2-Dioxetane probes for hydrogen sulfide.

FIG. 11.

1,2-Dioxetane probes for hydrogen sulfide and cysteine.