# Development of Transfer Hydrogenation Small-Molecule Intracellular Metal Catalysts (SIMCats) and their Application Toward Toxic Aldehyde Remediation

> **NIH NIH R01** · UNIVERSITY OF HOUSTON · 2021 · $306,000

## Abstract

PROJECT SUMMARY
Although small-molecule intracellular metal catalysts (SIMCats) offer potentially powerful new ways to
manipulate biological systems, several scientific barriers to their development have unfortunately limited their
use in life science research. The long-term goal of this project is to establish a comprehensive SIMCat
discovery program that focuses on their development and translation from the reaction flask to living systems.
The overall objectives of this research are to 1) identify the factors that are important to obtaining fast,
selective, and biocompatible transfer hydrogenation SIMCats; and 2) create new catalytic agents for the
remediation of aldehyde overload. We are interested in SIMCats that catalyze transfer hydrogenation reactions
because they mimic important redox enzymes that are ubiquitous in all life forms. Our central hypothesis is
that these synthetic enzyme mimics could be used to neutralize toxic aldehydes in vivo so that endogenous
antioxidants, such as glutathione, are free to sequester reactive oxygen species that damage cells and tissue.
The rationale for this project is that by selectively converting toxic aldehydes to non-toxic alcohols, transfer
hydrogenation SIMCats could supplement Nature’s defense system against oxidative stress. SIMCats are
expected to be highly efficient detoxification agents due to their ability to catalyze continuous reaction
turnovers, unlike conventional aldehyde scavengers that get consumed upon each reaction. In Specific Aim 1,
a variety of half-sandwich metal complexes will be tested for their activity and the most promising candidates
will be subjected to structure-activity relationship and kinetic/thermodynamic studies to obtain chemical insights
into their catalytic behavior. In Specific Aim 2, the catalytic rates, speciation, and distribution of SIMCats inside
live cells will be determined. This aim will be accomplished by taking advantage of single-molecule super
resolution microscopy and ratiometric fluorescence imaging techniques to visualize SIMCats “in action.” In
Specific Aim 3, the ability of transfer hydrogenation SIMCats to protect neuroblastoma cells and zebrafish
against aldehyde toxicity will be evaluated. The efficacy and aldehyde selectivity of SIMCat detoxification
agents will be compared to that of conventional stoichiometric aldehyde traps. The significance of our
research is the development of synthetic methodologies that are tailored toward the discovery of novel
SIMCats, which considers not only chemical reactivity and substrate selectivity but also biocompatibility. The
innovation of our research is the application of organometallic complexes to protect cells against chemical
toxicants by exploiting their catalytic capabilities. We expect that this work will help streamline the SIMCat
discovery process and lead to new approaches to remedy aldehyde overload, which could have important
therapeutic relevance to the treatment of oxidative stress-related ...

## Key facts

- **NIH application ID:** 10137265
- **Project number:** 5R01GM129276-02
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Loi Hung Do
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $306,000
- **Award type:** 5
- **Project period:** 2020-04-02 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137265

## Citation

> US National Institutes of Health, RePORTER application 10137265, Development of Transfer Hydrogenation Small-Molecule Intracellular Metal Catalysts (SIMCats) and their Application Toward Toxic Aldehyde Remediation (5R01GM129276-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137265. Licensed CC0.

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