Computational Study of Charged RO3280 and GSK461364

DFT calculations
were carried out for different charge states of RO3280 and GSK461364.
A previous conformational analysis was performed for the neutral state
of both drugs in the gas phase to obtain the lowest energy conformation.
The nature of the stationary points was assessed by means of normal
vibration frequencies calculated from the analytical second derivatives
of the energy. The PBE0 method^{14 (link)} as implemented
in Gaussian16 (revision C.01),¹⁵ along
with the 6–31G* and 6–31+G** basis sets, was used for
the conformational analysis and the subsequent optimization of the
molecular structure of the drugs in the neutral and charged states.
The 6–31+G** basis set is especially recommended in calculations
involving anionic species.¹⁶ The polarizable
continuum model (PCM) was employed to include the solvent (water)
effect.^{17 (link),18 (link)}The electronic vertical transitions
were calculated at the time-dependent (TD)-PBE0/6–31+G** level
(including solvent effects). TD-PBE0 has previously been successfully
employed to calculate low-energy transitions for BI-2636^{19 (link)} and other π-conjugated organic compounds.^{20 (link),21 (link)}