H2S Donor Compounds for Controlled Release via Biological Triggers
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional methods for delivering hydrogen sulfide (H2S) suffer from rapid metabolism and oxidation, leading to disruptive redox homeostasis, and existing slow-releasing donors do not allow for H2S to be triggered by biological responses, limiting their effectiveness in conditions like myocardial infarction or ischemia reperfusion injury.
Innovation Solution
Development of donor compounds that produce carbonyl sulfide (COS) or carbon disulfide (CS2), which can be converted to H2S, triggered by reactive components such as oxidants, reductants, or enzymes, allowing for controlled release of H2S in response to biological or chemical stimuli.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If direct administration of H2S or sulfide-containing salts is used, then H2S is quickly released, but it leads to large burst release and rapid metabolism/oxidation disrupting redox homeostasis
Solution Approach 1:
The patent applies preliminary action by designing donor compounds that are pre-configured with H2S in a stable, non-releasing form. The H2S is held in the compound structure (e.g., in thiocarbamate or similar moieties) and only released when the compound encounters specific biological triggers such as enzymes, pH changes, or reactive oxygen species. This preliminary preparation allows controlled release rather than immediate burst release, preventing redox homeostasis disruption while ensuring H2S is available when needed.
Solution Approach 2:
The patent uses intermediary compounds (the donor molecules themselves) that mediate between the stored H2S and the biological system. These intermediaries protect H2S from premature metabolism and oxidation by keeping it bound in stable chemical structures until triggered. The intermediary compounds convert stable, non-toxic forms into active H2S only at the target site, thereby avoiding systemic redox disruption while delivering therapeutic H2S levels.
2Duration of action of moving object
If slow-releasing H2S donors are used, then H2S is delivered at a sustained rate, but they do not allow for H2S to be triggered by biological responses
Solution Approach 1:
The patent applies dynamics by designing H2S donor compounds with dynamic release characteristics that adapt to biological conditions. The compounds are engineered to respond to specific biological triggers (enzymes, pH changes, redox state, reactive oxygen species) that naturally occur during pathological conditions like myocardial infarction or ischemia-reperfusion injury. This dynamic response allows the H2S release rate and timing to be controlled by the biological environment itself, providing both sustained delivery and biological adaptability.
Solution Approach 2:
The patent implements feedback mechanisms where the donor compounds respond to biological signals that indicate the need for H2S. For example, compounds may be designed to release H2S in response to increased reactive oxygen species, pH changes, or specific enzyme presence that occur during tissue injury. This feedback loop ensures H2S is released in response to actual biological needs rather than on a fixed schedule, providing both sustained action and biological responsiveness.
3Reliability
If H2S is released to protect against oxidative stress, then protection is provided, but rapid metabolism/oxidation occurs as a toxicological response
Solution Approach 1:
The patent uses intermediary donor compounds that mediate H2S delivery to protect against oxidative stress while avoiding toxicological responses. These intermediaries keep H2S in stable, non-reactive forms during circulation and storage, preventing premature oxidation and the associated toxicological response. Only when the compound reaches the target tissue and encounters appropriate triggers does H2S release occur, providing protective effects at the needed location without triggering systemic toxic responses.
Solution Approach 2:
The patent applies local quality by enabling H2S release at specific locations within the body rather than systemic release. The donor compounds are designed to release H2S in response to local biological conditions (such as enzyme presence, pH, or redox state) that are characteristic of diseased tissues. This localized release provides protective effects where needed while avoiding the toxicological responses that occur with systemic H2S administration, as the concentration remains low in healthy tissues.
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 a controlled and sustained release of H2S, mimicking enzymatic production, and provides protection against oxidative stress without disrupting redox homeostasis, with potential therapeutic applications in diseases associated with H2S misregulation or carbonic anhydrase overexpression.
Implementation Method 1
exposing the donor compound to a reactive component to release COS, CS2, H2S, or a combination thereof
Implementation Method 2
the reactive component is selected from an oxidant, a reductant, an enzyme, a nucleophile, light an acid, a base
Implementation Method 3
the reactive component is selected from an oxidant, a reductant, an enzyme, a nucleophile, light an acid, a base
Implementation Method 4
exposing the sample, released COS, released CS2, or a combination thereof to carbonic anhydrase, nitrogenase, RuBisCO, CO dehydrogenase, COSase, CS2 hydrolase, water, or a combination thereof
Implementation Method 5
the reactive component is selected from an oxidant, a reductant, an enzyme, a nucleophile, light an acid, a base
Data Source
AI summary
Disclosed herein are embodiments of donor compounds that can be used to produce H2S from COS or CS2 released from the donor compounds. In some embodiments, the donor compounds can indirectly produce H2S after being exposed to a reactive component in a triggering event. In other embodiments, the donor compounds can indirectly regenerate H2S after reacting with an H2S analyte. The donor compounds disclosed herein can be used for analytical techniques, disease diagnostics, and/or therapeutic applications. Methods of making and using the donor compounds also are provided herein.