Water as a field-effect transistor gate for dissipative biochemical systems

Developing universal, bidirectional strategies to control protein-protein interactions under isothermal and isohydric conditions remains a significant challenge. This work introduces a bioorthogonal supramolecular system, analogous to a chemical field-effect transistor (FET), for modulating dissipative biochemical systems by altering bulk water structure. The system employs the weakly coordinating superchaotrope dodecahydro-closo-dodecaborate ([B12H12]2-) to disrupt water's hydrogen bond network, thereby inhibiting protein-protein interactions without denaturation (gate-OFF). Sequestration of [B12H12]2- by γ-cyclodextrin derivatives (γCD) rapidly restores the solvent's permissive state, reinstating biochemical activity (gate-ON). We demonstrate broad, dose-dependent inhibition and reversible, multi-round modulation of diverse enzymatic reactions, including complex cascades like blood coagulation in human plasma. Furthermore, this solvent-mediated control is applied to preserve labile analytes in whole blood at ambient temperatures and to enhance macromolecular probe penetration in complex 3D biological systems by decoupling reaction from diffusion. This [B12H12]2-/γCD chemical FET offers a generalizable, indirect approach to control biochemical reactions by manipulating the solvent field itself.