# Novel Antidotes for H2S Poisoning

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $188,900

## Abstract

Hydrogen sulfide (H2S) is a highly-toxic chemical hazard in the gas and farming industry. It has also been used
as a chemical weapon, terrorists’ threat, and a method of suicide. Exposure to high levels of H2S has been
reported to cause acute neurotoxic, cardiovascular, and respiratory effects, as well as persistent neurologic
deficits and neurodegeneration. Many victims are found in cardiopulmonary arrest at the scene requiring
cardiopulmonary resuscitation (CPR) with dismal outcomes. Currently, there is no specific antidote for H2S
intoxication. Although nonspecific scavengers such as hydroxocobalamin have been investigated as antidote
for H2S intoxication, these compounds scavenge not only H2S, but also cyanide, nitric oxide (NO), and CO.
Because NO and CO are important signaling molecules, nonspecific scavenging may have adverse effects.
Development of more specific H2S scavengers should enhance our ability to counter H2S intoxication.
However, to the best of our knowledge, specific H2S scavengers have not been systematically explored. Here,
we propose a data-driven identification of specific H2S scavengers and initial characterization. The criteria of
‘ideal’ H2S scavengers are: 1) highly reactive to H2S, 2) highly selective to H2S, 3) negligible biological activity,
and 4) structural flexibility for modifications. These criteria are very much the same as the criteria for H2S
sensors/fluorescent probes. Xian laboratory has recently constructed a comprehensive on-line searchable
database on H2S fluorescent sensors (http://sensor.eecs.wsu.edu/index/). It covers all reported sensors with
key parameters. Because the most critical parameter of effective scavengers is their reactivity toward H2S,
which is determined by the H2S-reaction site, we analyzed the time needed for the sensors to complete the
reaction with H2S and group them based on their specific H2S-reactive sites. We identified 9 major types: 1)
benzoxadiazole based sensors, 2) aryl nitro based sensors, 3) aryl azide based sensors, 4) 2,4-dinitro
benzene based sensors, 5) aldehyde-based sensors, 6) disulfide linkage based sensors, 7) sulfonyl azide
based sensors, 8) indolium based sensors, and 9) selenium oxide based compounds. Based on in vitro and
cell-based screening assays, we identified sulfonyl azide-based and selenium oxide-based compounds as
promising H2S scavengers. To start characterizing in vivo efficacy of candidate compounds, we examined
effects of one sulfonyl azide-based compound SS-20 in a mouse model of H2S intoxication. While less than
50% of vehicle-treated mice survive after H2S poisoning, all mice treated with SS-20 survived. These
preliminary results suggest that H2S sensors may function as effective antidotes for H2S poisoning. To screen
and identify lead compounds for further development, we specifically propose to screen additional candidate
compounds and identify lead candidate H2S scavengers for further development (Specific Aim 1), and to
examine the antidot...

## Key facts

- **NIH application ID:** 10147782
- **Project number:** 5R21NS116671-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** FUMITO ICHINOSE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,900
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147782

## Citation

> US National Institutes of Health, RePORTER application 10147782, Novel Antidotes for H2S Poisoning (5R21NS116671-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10147782. Licensed CC0.

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