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Lookup NU author(s): Dr Matt HopkinsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The combinatorial explosion inherent to multi-component systems limits their experimental exploration and ultimately chemical discovery. Here, we introduce a statistics-based group-testing strategy, which we couple with luminescence quenching assays to efficiently identify cooperative molecular interactions. Utilizing the quenching of a photosensitizer as a quick readout for chemical activity, 4,950 substrate pairs were screened in only 504 experiments, enabled through a combinatorial design theory-based pooling approach and iterative deconvolution. Therefore, two algorithms—a greedy algorithm for group design and an iterative sectioning deconvolution method to resolve active pairs—were implemented. Fifteen cooperative pairs were identified, and the nature of their interactions and the resulting electronic perturbations were investigated. In a systematic follow-up screen, it was found that the identified active pairs exhibit high reactivity towards a broad group of reaction partners. One such pair led to the discovery of a bench-stable reagent, enabling efficient and regioselective trifluoromethylthiolation reactions. This work establishes a broadly applicable framework for accelerating the discovery of cooperative reactivity through optimized experimental designs.
Author(s): Pflüger PM, Katzenburg F, Sandfort F, Teders M, Gómez-Suárez A, Standley EA, Hopkinson MN, Daniliuc CG, Heuer A, Glorius F
Publication type: Article
Publication status: Published
Journal: Angewandte Chemie International Edition
Year: 2026
Volume: 65
Issue: 11
Print publication date: 09/03/2026
Online publication date: 03/02/2026
Acceptance date: 20/01/2026
Date deposited: 02/06/2026
ISSN (print): 1433-7851
ISSN (electronic): 1521-3773
Publisher: Wiley
URL: https://doi.org/10.1002/anie.202525278
DOI: 10.1002/anie.202525278
Data Access Statement: Detailed descriptions of all performed experiments, as well as compu- tational details, are given in the Supplementary Information. Crystallo- graphic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre under deposition num- bers CCDC 2049022 (3b) and 2049023 (9c). Copies of the data can be obtained free of charge at https://www.ccdc.cam.ac.uk/structures/ . All other data supporting the findings of this study are available within the article and its Supplementary Information, or from the corresponding author upon request. The source code of the algorithms developed and used in this work is available at https://zivgitlab.uni-muenster.de/ag- glorius/published-paper/coop_screen . A Python implementation extend- ing the greedy group design algorithm to triples and higher coverages is available at https://github.com/FelixKatz77/GroupDesign .
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