Thermodynamics of surface defects at the aspirin/water interface

Abstract

We present a simulation scheme to calculate defect formation free energies at a molecular crystal/water interface based on force-field molecular dynamics simulations. To this end, we adopt and modify existing approaches to calculate binding free energies of biological ligand/receptor complexes to be applicable to common surface defects, such as step edges and kink sites. We obtain statistically accurate and reliable free energy values for the aspirin/water interface, which can be applied to estimate the distribution of defects using well-established thermodynamic relations. As a show case we calculate the free energy upon dissolving molecules from kink sites at the interface. This free energy can be related to the solubility concentration and we obtain solubility values in excellent agreement with experimental results.

Efficient Calculation of Microscopic Dissolution Rate Constants: The Aspirin–Water Interface

“…12,13 This prevents a low-dimensional description of the reaction pathway and concomitantly regular transition-state theory (TST)-type approaches 14 that are based on free energy profiles along corresponding reaction coordinates. 9 (iii) The individual transition between bound and dissolved states involves substantially changing entropic contributions, 15 excluding simple reaction barrier estimates based on bond-breaking energies that otherwise sufficiently determine, for instance, relative ratios of different rate constants. 5,13 Aiming for a method that is both quantitatively reliable and numerically efficient, we here propose to overcome these challenges by combining hyperdynamics 16 with metadynamics 17 simulations.…”

“…This aspect becomes particularly beneficial for the present bound-to-free transition and the associated largely changing entropic contributions. 15 Moreover, the separation of the two steps allows us to control that the bias potential always vanishes in the barrier region. Therefore, the trajectory segments that follow the first barrier crossing can be exploited to explicitly calculate a transmission coefficient κ to additionally account for recrossing effects.…”

“…(ii) The rotational degrees of freedom of the noncentrosymmetric molecular dissolution unit adds additional complexity to the reaction coordinate. , This prevents a low-dimensional description of the reaction pathway and concomitantly regular transition-state theory (TST)-type approaches that are based on free energy profiles along corresponding reaction coordinates . (iii) The individual transition between bound and dissolved states involves substantially changing entropic contributions, excluding simple reaction barrier estimates based on bond-breaking energies that otherwise sufficiently determine, for instance, relative ratios of different rate constants. , …”

“…Instead we are able to focus only on the forward reaction. This aspect becomes particularly beneficial for the present bound-to-free transition and the associated largely changing entropic contributions . Moreover, the separation of the two steps allows us to control that the bias potential always vanishes in the barrier region.…”

In Silico Prediction of Growth and Dissolution Rates for Organic Molecular Crystals: A Multiscale Approach

“…However, the authors stressed that the approach does not allow computing absolute growth rates. The Reuter group also established a method for a quick prediction of approximate dissolution rates at low undersaturation based on the combination of hyperdynamics and metadynamics approaches [29][30][31]. This method relies on the classic rotating spiral model of Burton, Cabrera and Frank (BCF) [32], which assumes that dissolution (growth) proceeds via rotating spirals of step edges at screw dislocations and that dissolution (incorporation) of molecular units takes place primarily at kink defects along these step edges.…”