The interaction between 9-fluorenone (9F) and various indoles in different types of solvents (polar protic and polar aprotic) has been studied using both quantum chemical calculations and steady-state fluorescence experiments. Fluorescence quenching of fluorenones by both solvents and indoles and the competition between the two quenching effects was examined using steady-state fluorescence spectroscopy. Consistent with previous studies, it was found that polar protic solvents such as methanol, ethanol, and water significantly quenched the fluorescence of 9F but the addition of indoles reversed the solvent quenching. In polar aprotic solvents the indoles quenched the fluorescence of fluorenone. It was also observed that in binary solvent systems, there was competition between indole-quenching and solvent-quenching. A Stern-Volmer analysis was carried out to determine quenching constants. Ab initio calculations using Gaussian03 were also carried out in order to determine the minimum energy conformations of these systems as well as binding energies and intermolecular distances. Further computational studies investigating solvent effects are currently underway with the goal of comparing binding energies of substituted fluorenones with a series of solvents of varying polarity. One substituted fluorenone of interest is 9-fluorenone-2-carboxylic acid (9F2C) which is known to cross-link proteins via a multi-photon excitation process and these studies are designed to further characterize and understand the interaction between the photoactivator and the protein.