Density Functional Theory (DFT) Calculations

All calculations were performed by the ORCA 5.0.3 quantum chemistry package.^36,37 The hybrid functional B3LYP with the Pople basis set 6-311++G(2df,2dp) with dispersion correction (Becke Johnson damping scheme) was used to optimize the 3-ethyl-indole (3EI) systems (3EI with or without explicit water and with or without various implicit solvents) to their equilibrium geometry.^38,39 B3LYP/6-311++G(2df,2dp) was also used to calculate the vibrational frequencies of the 3EI systems. There were no virtual frequencies, confirming the systems were at a local minimum of the potential energy surface. For systems with implicit solvent, the conductor-like polarizable continuum model (CPCM), as implemented in ORCA 5.0.3, was used to incorporate several different implicit solvents (water, methanol, and cyclohexane)⁴⁰ for the optimization of the system geometry and the calculation of the vibrational frequencies.