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

• Published in: Computational and theoretical chemistry 2016-07, Vol.1088, p.52-61
• Main Authors: Rychkov, Denis A., Hunter, Steven, Kovalskii, Viktor Yu, Lomzov, Alexander A., Pulham, Colin R., Boldyreva, Elena V.
• Format: Article
• Language: English
• Subjects: 5-HT; Crystallization mechanism; DFT; Potential energy surface; Serotonin; Transition states
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2016.04.027

[Display omitted] •A potential energy surface was calculated for the 5-HT molecule in aqueous media.•Minima and TS were located using fully relaxed optimization at different LOT.•5-HT conformational and lattice energies of serotonin salts were calculated.•Comparison of conformations in crystals and crystallisation media were preformed.•New approach for crystal structure prediction using conformational study is suggested. 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 23kJmol−1. Lattice energies of serotonin picrate monohydrate and serotonin adipate were calculated as −741.7 and −716.9kJmol−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.