Lyle Isaacs
University of Maryland, MD·Chemistry
Drugs, both prescription and illicit, and environmental toxins can linger in the body and cause disease or death. One way to counter them is to trap the harmful molecule itself.
- Fields
Chemistry
Pharmacology
Biomedical Engineering
- Topics
supramolecular chemistry
molecular containers
host-guest chemistry
- Grants
- 3 known grants, through Jul 2029
What they work on
- Synthesize acyclic cucurbit[n]uril (CB[n]) containers that vary in glycoluril building blocks, aromatic walls and solubilizing groups, and map how each change alters binding strength toward drugs and toxins in buffered water.
- Use an experiment–computation feedback loop with collaborators, and supply blinded CB[n] binding datasets to the SAMPL challenges, to improve computer predictions of how tightly molecules bind in water.
- Design water-soluble macrocyclic arenes (prismarenes and pagodaarenes) with optimized charged groups and cavity size, guided by molecular modeling, to tightly bind drugs of abuse such as fentanyl, cocaine and methamphetamine.
- Establish the safety of new drug-binding containers through in vitro toxicology and in vivo maximum tolerated dose studies, then test their antidote effect using hyperlocomotion assays in animals.
- Uncover why pillararene sulfates bind cationic guests up to 10,000-fold more tightly than WP6, by varying their structure and measuring binding with NMR, X-ray crystallography, fluorescence and isothermal titration calorimetry.
- Prepare pillararene sulfates with a single reactive group so they can be attached to polymers and solid supports, and test them in sensing, separation and sequestration systems.
More about the research
A "molecular container" is a ring- or bowl-shaped molecule with a cavity that grabs a smaller guest molecule in water and holds it tightly. Across three projects, the lab designs and synthesizes new families of these containers. It measures how strongly and how selectively each one binds positively charged (cationic) guests, then tests the best ones as antidotes, delivery agents, sensors and cleanup tools.
Why it matters
People who overdose on fentanyl, cocaine, methamphetamine, ketamine or PCP currently have limited or no specific antidotes, and drug abuse costs the U.S. billions in healthcare each year. Container molecules that bind a drug in the bloodstream could become broad antidotes that lower deaths and costs. Related hosts may also remove toxins from the gut or blood, deliver drugs, detect chemicals, or clean up pollutants. The lab's binding datasets could also help improve computer methods for predicting how molecules bind in water.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jovica Badjic
Ohio State University, OH·Chemistry
Synthesize polyanionic, dendritic pillar[6]arenes with stable pS or pR planar chirality and a nonpolar pocket shielded by anionic groups, and test their ability to bind chiral steroids differing in charge and number of stereocenters in water.
Wenqi Liu
University of South Florida, FL·Chemistry·Early-career
Design and synthesize acyclic (open-chain) receptors that use ion-dipole and electrostatic interactions to bind lithium ions selectively over competing metal ions, and measure their binding in solution.
Renjie Wang
Florida Atlantic University, FL·Chemistry
Measure how commonly encountered PFAS molecules bind nucleic acids of varying base composition, testing whether binding preference tracks with carbon-chain length and chemical functional group.
The school
University of Maryland: 49 labs on PI Pages, $1.5B a year on research, 602 research doctorates a year.
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