H2S Donor Compounds for Controlled Release via COS and CS2 Intermediaries

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Solution Overview

Problem

Current methods for delivering hydrogen sulfide (H2S) suffer from uncontrolled release and rapid metabolism, leading to toxicological responses and difficulties in maintaining elevated H2S levels for therapeutic purposes.

Innovation Solution

Development of a donor compound capable of triggered release of carbonyl sulfide (COS) or carbon disulfide (CS2), which can be converted to H2S, allowing for controlled delivery through deprotonation and elimination reactions, and functionalization with detectable moieties or therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If direct administration of H2S or sulfide-containing salts is used, then H2S delivery is convenient, but H2S is quickly metabolized/oxidized leading to toxicological responses and disruption of redox homeostasis

Engineering Contradiction:

Improveconvenience of H2S deliveryVSAvoidtoxicological response and redox homeostasis disruption

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent uses COS and CS2 as intermediary compounds that are more stable than direct H2S administration. These intermediaries are converted to H2S by endogenous enzymes (carbonic anhydrase for COS, and various hydrolases for CS2), providing controlled H2S delivery while avoiding the immediate toxic effects of direct H2S or sulfide salt administration.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention employs prodrug-like compounds (COS and CS2 donors) that are administered in stable forms and then converted to active H2S in vivo. This preliminary action allows the compound to reach the target site in a stable state before being activated, preventing premature metabolism and toxicological responses associated with direct H2S administration.

Inventive Principle:

Principle #10Preliminary action

2Quantity of substance

If direct H2S administration is used, then immediate H2S levels increase, but the burst release is quickly metabolized resulting in merely disruption of redox homeostasis rather than sustained elevated H2S levels

Engineering Contradiction:

ImproveH2S concentrationVSAvoidduration of elevated H2S levels

Core Design Contradiction:

Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The patent employs compounds that release H2S in a controlled, periodic manner rather than a single burst. The deprotonation and elimination reactions occur progressively, maintaining elevated H2S levels over an extended period. This periodic release pattern prevents rapid metabolism and allows sustained therapeutic H2S concentrations.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The stable COS and CS2 donor compounds are administered first, then progressively converted to H2S through enzymatic reactions. This preliminary action creates a reservoir of stable compounds that continuously generate H2S, extending the duration of elevated H2S levels beyond what is achievable with direct administration.

Inventive Principle:

Principle #10Preliminary action

3Duration of action of moving object

If donor compound releases COS or CS2 through deprotonation and elimination, then controlled and sustained H2S release is achieved, but the compound must be stable against nucleophilic attack

Engineering Contradiction:

Improvesustained H2S release durationVSAvoidstability against nucleophilic attack

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent designs donor compounds with specific structural features that provide differential stability: the compounds are stable against nucleophilic attack in the bloodstream and extracellular environment, but undergo controlled deprotonation and elimination at the target site where pH or enzymatic conditions favor the release reaction. This local quality differentiation allows sustained release while maintaining reliability.

Inventive Principle:

Principle #3Local quality

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables controlled and sustained release of H2S, facilitating therapeutic applications by providing a platform for treating diseases associated with H2S deficiency or misregulation, while avoiding premature release and ensuring stability against nucleophilic attack.

Implementation Method 1

capable of releasing COS and/or CS2 and thus can act as H2S donors through deprotonation and elimination reactions

Methodology Applied

Scientific EffectDeprotonation:

Implementation Method 2

capable of releasing COS and/or CS2 and thus can act as H2S donors through deprotonation and elimination reactions

Methodology Applied

Scientific EffectElimination reaction:

Implementation Method 3

COS or CS2—both of which can be converted to hydrogen sulfide (H2S)

Methodology Applied

Scientific EffectChemical conversion:

Data Source

PatentUS11981626B1Compound embodiments for hydrogen sulfide production and methods of making and using the same

Publication Date: 2024.05.14 FLAMEL IRELAND

AI summary

Disclosed herein are embodiments of a donor compound that releases COS and/or CS2, which can be converted to H2S. The donor compound embodiments described herein can be used to deliver H2S to a subject or a sample and further can be used to administer therapeutic agents. Methods of making and using the donor compound embodiments also are disclosed.