Towards an understanding of crystallization from solution. DFT studies of multi-component serotonin crystals

A potential energy surface (PES) has been calculated for the protonated serotonin (5-HT) molecule in aqueous media. Three pairs of symmetrically equivalent minima were located using fully relaxed optimization at B3LYP/6-31G(d,p) level of theory. Insensitivity to basis set was verified over a range of different functionals and levels of theory. All 9 transition structures were found using the QST3 method with ansatz structures taken directly from the result of the calculated PES. Energies associated with conformational changes of protonated 5-HT in aqueous media were calculated and found to vary between 6 and 23 kJ mol^-1. Lattice energies of serotonin picrate monohydrate and serotonin adipate were calculated as -741.7 and -716.9 kJ mol^-1, respectively, and compared to conformational energies to consider the relative importance of each interaction type. The study contributes to achieving better insight into the importance of molecular conformations in solution as a precursor for the formation of the final crystal structure.