Methods of Detection, Delivery, and Quantification of Biological Hydrogen SulfideHydrogen sulfide (H2S), historically known for its unpleasant rotten-egg smell, is now accepted as an important physiological mediator and signaling agent, joining CO and NO as an endogenous gasotransmitter. Despite its recent emergence as an important biological molecule, investigations have already revealed important physiological and pathological functions of H2S including roles in diabetes, hypertension, heart failure, inflammation, and neurodegeneration. As the complex biochemical functions of H2S continue to rapidly emerge, the development, refinement, and application of robust, reliable and purpose-inspired chemical tools for studying its multifaceted roles are paramount. Aligned with this need, our group is developing new chemical tools to detect and modulate biological H2S. Such tools include fluorescent, chemiluminescent, and colorimetric methods for H2S detection and quantification as well as slow-releasing H2S donors modulated by biological stimuli. Drawing parallels to the positive impacts of chemical tools for detection, quantification, and delivery of biological NO, we anticipate that these newly-developed chemical tools will enable new investigations into the multifaceted roles H2S in biology.
Probing the Reactions of Hydrogen Sulfide with Biological TargetsDespite the important and diverse roles of biological H2S, little is known about the fundamental chemistry by which H2S exerts its action on discrete biological targets. Unlike gasotrasmitters NO and CO, the physiologically-accessible protonation states of H2S complicate its reactivity, but also allow for modulation of its water/lipid solubility, nucleophilicity, and reduction potential. Aligned with these physicochemical properties, most biological actions of H2S are proposed to occur through interaction with either bioinorganic transition-metal complexes or with sulfur-containing compounds. Despite the substantial consensus regarding the importance of these chemical pathways, significant controversy remains regarding the fundamental chemistry associated with these interactions. Motived by these unmet needs, we are investigating the mechanisms by which H2S reacts with biomimetic transition-metal and organosulfur compounds by using small-molecule systems to simplify the observed reactivity. By simplifying the molecular architectures involved in this chemistry and studying individual interactions, our long-term goal is to develop and use model systems that allow for greater understanding into the fundamental chemistry associated with the storage, translocation, and action of biological H2S.
Hybrid Metal-Ligand Hydrogen-Bonding Supramolecular ArchitecturesInspired by the remarkably complex structures generated from Nature’s simple catalog of assembly components, chemists have devised different strategies to harness molecular self-assembly and develop diverse supramolecular constructs. Unlike Nature, however, chemists are not constrained to natural amino acids, bioinorganic metal ions, or the requirements to work in water at physiological pH. By leveraging this expanded chemical space and by using pre-designed components encoded with different chemical information, such as shape, symmetry, directional bonding, and makeup of functional groups, chemists have generated diverse supramolecular architectures held together by metal-ligand or hydrogen-bonding interactions. Despite the breadth of complexes and chemistries generated from the hydrogen-bonding and metal-ligand assembly strategies individually, the interface between these two assembly domains remains underexplored. This underexplored niche offers the prospect of combining different beneficial properties from each assembly strategy to develop new supramolecular complexes and chemistries. To fill this niche, we are designing different ligand components that encoded metal-ligand and hydrogen-bonding motifs to generate pre-designed, functional, self-assembled structures aimed at studying supramolecular dynamics and catalysis. Results from these studies will provide new hybrid supramolecular constructs and rational design methods for combining metal-ligand and hydrogen-bonding interactions to generate pre-designed molecular architectures.
(pulled from pubmed)
(pulled from pubmed)