Expanding the Organoiridium Catalyst Design Space Using Sulfur-Containing Bioisosteres
Hoang T Dang1, Hieu D Nguyen1, Kanika Kaushal1
1Department of Chemistry, University of Houston, 4800 Calhoun Rd., Houston, Texas77004, United States.
Inorganic Chemistry
|July 16, 2026
Summary
Bioisostere modification of iridium complexes enhances biocompatible transfer hydrogenation catalysis. The N,N-chelated iridium complex (Ir4) shows promising activity and cellular compatibility for intracellular catalysis.
Area of Science:
- Organometallic Chemistry
- Catalysis
- Medicinal Chemistry
Background:
- Half-sandwich iridium complexes show potential as intracellular catalysts.
- Limited biocompatible catalysts exist for transfer hydrogenation in living systems.
- Expanding catalyst design space is crucial for biological applications.
Purpose of the Study:
- To develop novel biocompatible iridium catalysts for transfer hydrogenation.
- To explore the impact of bioisosteric modification on catalyst activity and cellular uptake.
- To identify promising candidates for intracellular catalysis.
Main Methods:
- Synthesized N,S-chelated (Ir2/Ir3) and N,N-chelated (Ir4) iridium complexes by replacing the 2-pyridylamidate donor in the parent complex (Ir1).
- Evaluated catalytic activity in the reduction of benzaldehyde to benzyl alcohol using sodium formate in a DMSO/H2O mixture.
- Assessed biocompatibility by measuring 50% inhibition concentrations in mammalian cells and predicting membrane diffusability.
Main Results:
- Catalytic activity followed the trend Ir1 > Ir4 > Ir3, with sulfur-containing analogues showing reduced activity.
- Nonsulfur analogues (Ir3', Ir4') yielded only trace products.
- Complexes Ir3 and Ir4 exhibited higher 50% inhibition concentrations than Ir1 in mammalian cells, despite predicted differences in membrane diffusability.
Conclusions:
- Bioisosteric modification is a powerful strategy for creating diverse iridium catalysts with retained function.
- The N,N-chelated complex Ir4 demonstrates superior biocompatibility and catalytic activity, making it a promising candidate for intracellular catalysis.
- This approach opens new avenues for developing metallodrugs and advancing biotechnology.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Related Concept Videos
02:26Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
01:22Bioreactor Controls-III
Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
01:22Heterogeneous Catalysis
Heterogeneous catalysis involves a catalyst in a different phase from the reactants. It is a process where the catalyst and the reactants are in distinct phases, typically solid and gas or liquid.Most heterogeneous catalysts are metals, metal oxides, or acids. The list includes transition metals like iron (Fe), cobalt (Co), nickel (Ni), palladium (Pd), platinum (Pt), chromium (Cr), manganese (Mn), tungsten (W), silver (Ag), and copper (Cu). These metals possess partially vacant d orbitals that...
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:20Sulfur Assimilation
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to become...