# Sulfur(VI) Fluoride Exchange (SuFEx): new developments and biological applications

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2022 · $443,750

## Abstract

PROJECT SUMMARY/ABSTRACT
 The central goal of this project is to develop new sulfur fluoride exchange (SuFEx) reactions to construct
small-molecule libraries containing the SVI-F motif and to explore their in vitro and in vivo functions. SuFEx is a
new family of click chemistry transformations for generating diverse chemical structures bearing the SVI-F
motif, such as -OSO2F (fluorosulfate) and -SO2F (sulfonyl fluoride).
 In the last funding period, we established three versatile SulfurVI connectors: sulfuryl fluoride (SO2F2),
ethenesulfonyl fluoride (ESF) and thionyl tetrafluoride (SOF4), among which SO2F2 selectively reacts with the –
OH group of phenols to form aryl fluorosulfates. Based on this transformation, we invented extremely fast
fluoride exchange reactions to introduce the fluorine-18 isotope into biologically active small-molecule
radiotracers for positron emission tomography. By screening aryl fluorosulfate-based libraries, we discovered
small-molecule covalent modifiers for Intracellular Lipid Binding Protein(s) and a platform for the late-stage
drug functionalization.
 Based on these discoveries, in the next funding period, we will develop new transformations to expand
the SuFEx transformation repertory (Aim 1). Using these new synthetic strategies and our established SuFEx
tools, we will design and synthesize new SVI-18F agents based on amine-containing probes for positron
emission tomography (Aim 2). Finally, using SuFEx chemistry, we will prepare small-molecule libraries and
screen them to identify new antibiotics candidates and anti-cancer compounds (Aim 3).

## Key facts

- **NIH application ID:** 10331051
- **Project number:** 5R01GM117145-07
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** KARL BARRY SHARPLESS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $443,750
- **Award type:** 5
- **Project period:** 2016-01-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331051

## Citation

> US National Institutes of Health, RePORTER application 10331051, Sulfur(VI) Fluoride Exchange (SuFEx): new developments and biological applications (5R01GM117145-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10331051. Licensed CC0.

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