The integrated DL_POLY/DL_FIELD/DL_ANALYSER software platform for molecular dynamics simulations for exploration of the synthonic interactions in saturated benzoic acid/hexane solutions

ABSTRACT

Three separately developed software Molecular Dynamics packages at Daresbury Laboratory, namely DL_FIELD (DL_F), DL_POLY and DL_ANALYSER, have been integrated to form an efficient computational infrastructure to investigate the detailed solution chemistry of saturated benzoic acid in hexane solutions. These software capabilities are demonstrated, in combination with the Synthonic Engineering tools and density functional theory (DFT) calculations, to assess the extent that the solute-solute intermolecular synthonic interactions in solution mirrors the synthons in the crystal structure. The results show that the majority of the COOH groups are forming OH … O H-bonds, which are a combination of classic OH … O homo-dimers and three membered H-bonding clusters. The formation of pi-pi stacking interactions is observed, but in far fewer numbers than observed for the OH … O interactions. The DFT simulations of the IR spectra of the multiple benzoic acid aggregates extracted from the MD trajectories provides further in-depth analysis of previously published IR data, by matching simulated peaks to the experimental peaks, hence identifying the exact bonding modes that are responsible for such peaks. This study demonstrates the value of a multi-scale and multi-technique approach to exploring the molecular transition pathway from solution to crystal structure.

KEYWORDS:

• solution synthon chemistry
• molecular dynamics
• DFT
• benzoic acid
• DL_POLY

Acknowledgments

We gratefully acknowledge the support of the Advanced Manufacturing Supply Chain Initiative through the funding of the ‘Advanced Digital Design of Pharmaceutical Therapeutics’ (Grant No. 14060) project in terms of supporting pharmaceutical crystallisation and modelling research at Leeds. We are also grateful to the funding of the EPSRC for some of the development of DL_ANALYSER under the auspices of the EPSRC's Collaborative Computational Project No. 5 (CCP5), of grant no: EP/M022617/1.

We are also grateful to the EPSRC for the support of crystallisation research at Leeds and Manchester through the award of a Critical Mass grant ‘Molecules, Clusters and Crystals’ (EP/I014446/1).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Engineering and Physical Sciences Research Council [grant number EP/I014446/1, EP/M022617/1]; Advanced Manufacturing Supply Chain Initiative [grant number 14060].