We investigated the stability of
oxyluciferin anions (keto, enol,
and enolate isomers) in aqueous solution at room temperature by performing
a nanosecond time scale first-principles molecular dynamics simulation.
In contrast to all previous quantum chemistry calculations, which
suggested the keto-type to be the most stable, we show that the enol-type
is slightly more stable than the keto-type, in agreement with some
recent experimental studies. The simulation highlights the remarkable
hydrophobicity of the keto-type by the cavity formed at the oxyluciferin–water
interface as well as a reduction in hydrophobicity with the number
of hydrating water molecules. It is therefore predicted that the isomeric
form in a hydrated cluster is size-dependent.