Protonated serotonin conformational landscape in vacuo and in aqueous solution (IEF-PCM): Role of correlation effects and monohydration

Abstract

The conformational landscape of protonated serotonin has been explored in the gas phase and aqueous solution (IEF-PCM) with full geometry optimization at the HF and MP2 levels using the 6-31G* basis set. Single point calculations carried out up to the QCISD( T)/6-31G* level on the HF/6-31G* optimized structures find two low energy gauche conformations (G2 and G1) and a trans conformation (T) higher in energy by about 6 kcal/mol. Optimized calculations up to the HF/6-311++G** level somewhat reduce the barrier heights with respect to the HF/6-31G* ones of G2 and G1 to T (7–8.5 kcal/mol) whose relative energy is about 4.5 kcal/mol less favorable than the gauche conformers. Both trends are smoother than that obtained including MP2 correlation corrections at the 6-31G* level, where the T structure turns out about 7.3 kcal/mol higher in energy than the most stable gauche conformation (G2) with barrier heights of about 10–12 kcal/mol. In aqueous solution G1 and primarily T are significantly stabilized with respect to G2, that becomes the least stable minimum according to IEF-PCM/HF and MP2/6-31G* continuum solvent calculations in water, while the barriers decrease to 3–5 kcal/mol. The results obtained have been compared to earlier DFT results at the B3LYP/6-31G* level [J. Chem. Theory Comput. 1 (2005) 801]. Singly hydrated adducts have been considered both at the CP-corrected level or not, the latter embedded in the continuum solvent as well. Geometry optimizations in solution of monohydrated complexes put forward non-negligible solvent effects on the supermolecule structure and the related differential stabilization due to bulk solvent.