Solubility Prediction of Organic Molecules with Molecular Dynamics Simulations


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Date

2021-09-01

Publication Type

Journal Article

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Abstract

We present a molecular dynamics simulation method for the computation of the solubility of organic crystals in solution. The solubility is calculated based on the equilibrium free energy difference between the solvated solute and its crystallized state at the crystal surface kink site. To efficiently sample the growth and dissolution process, we have carried out well-tempered metadynamics simulations with a collective variable that captures the slow degrees of freedom, namely, the solute diffusion to and adsorption at the kink site together with the desolvation of the kink site. Simulations were performed at different solution concentrations using constant chemical potential molecular dynamics, and the solubility was identified at the concentration at which the free energy values between the grown and dissolved kink states were equal. The effectiveness of this method is demonstrated by its success in reproducing the experimental trends of solubility of urea and naphthalene in a variety of solvents.

Publication status

published

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Volume

21 (9)

Pages / Article No.

5198 - 5205

Publisher

American Chemical Society

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Organisational unit

03484 - Mazzotti, Marco (emeritus) / Mazzotti, Marco (emeritus) check_circle

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