A General Group Testing Strategy for Discovering Chemical Cooperativity.

Area of Science:

• Chemistry
• Chemical Biology
• Materials Science

Background:

• Multi-component chemical systems present a combinatorial challenge for experimental screening.
• Discovering cooperative molecular interactions is crucial for advancing chemical synthesis and discovery.
• Traditional screening methods are often inefficient for exploring vast chemical spaces.

Purpose of the Study:

• To develop an efficient strategy for identifying cooperative molecular interactions within multi-component systems.
• To accelerate the discovery of novel chemical reactivity and reagents.
• To overcome the limitations of combinatorial explosion in chemical exploration.

Main Methods:

• A statistics-based group-testing strategy was coupled with luminescence quenching assays.
• Combinatorial design theory-based pooling and iterative deconvolution were employed.
• Two algorithms, a greedy algorithm for group design and iterative sectioning for deconvolution, were implemented.

Main Results:

• Screened 4,950 substrate pairs in only 504 experiments, identifying 15 cooperative pairs.
• Identified active pairs demonstrated high reactivity with various reaction partners.
• Discovered a bench-stable reagent for efficient and regioselective trifluoromethylthiolation.

Conclusions:

• The developed group-testing framework significantly accelerates the discovery of cooperative reactivity.
• This approach provides a broadly applicable method for optimizing experimental designs in chemical discovery.
• The identified cooperative pairs and novel reagents open new avenues in synthetic chemistry.