Gas Phase ab initio DFT Calculations for BA-VitC Cocrystal Formation

This method is based on the calculation of gas phase MEP for the proposed structures, followed by the conversion of local MEP maxima and minima into SSIPs, α and β, that describe the potential H-bond interaction sites (Musumeci et al., 2011; Grecu et al., 2013). Structure geometry optimization and DFT calculations were employed by using the GAMESS software while MEPS were generated using MacMolPlt and Avogadro. Geometry optimization and MEP for both structures were achieved by ab initio gas phase DFT calculations, at the B3LYP 6-31G(d) level of theory. Local MEP maxima and minima were converted in SSIPs using the following equations (Equations 1, 2) (Musumeci et al., 2011);

where:

MEP_max and MEP_min represent local maxima and minima (energy values were given in Hartrees)

Calculated SSIPs were paired for the pure structures and the cocrystal as follows: the highest α values interact with the highest β values, the second highest α value interact with the second highest β and so on. After α/β pairing, the total interaction site energy for the pure solids and cocrystal was estimated using Equation (3) (Musumeci et al., 2011). Energy values were converted from Hartrees into kJ/mol.

The calculated energy difference between the interaction site pairing energies of the cocrystal and the two pure forms (Equation 4) provides a probability measure for a cocrystal formation (1:1) based on the assumption that within the cocrystal more favorable interactions will be formed.

where:

E_ccry is the calculated interaction energy of the cocrystal,

E_a and E_b are the calculated interaction energies for the pure structures, and

x,y represent the molar ratio of the two structures within the cocrystal.