The Solvent as an Active Electrostatic Component in Transition State Design

Reconceptualize solvent molecules as active participants in the transition state assembly rather than passive media. Design solvent mixtures containing specifically shaped and polar protic molecules that fit into catalyst-substrate complexes (e.g., CPA-catalyzed reactions) to form key hydrogen bonds or dipole interactions that stabilize one transition state over another. Use computational electrostatic modeling to co-design catalysts and solvent molecules as a single functional unit, transforming solvent selection into a precise tool for stereocontrol and moving beyond traditional considerations of solubility and green credentials.

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