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Morphological Prediction of the Polymorphic Forms of Para Amino-Benzoic Acid Based on Internal Crystallographic Structure and Crystallisation Environment |
| Ian Rosbottom , Kevin J. Roberts , Robert B. Hammond , Majeed Soufian |
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University of Leeds (SPEME), Leeds LS2-9JT, United Kingdom |
| Abstract |
| The shape of crystals is an important factor in processing crystalline products. Many industries including pharmaceuticals, fuels and fine chemicals process products using techniques such as filtering and milling where the morphology of the crystals is very important. The work presented forms part of the joint Critical Mass project between the University of Leeds and University of Manchester focused on understanding the process by which molecules cluster in solution, nucleate and grow to macroscopic crystals. In this case the morphology of para amino-benzoic acid (PABA) is predicted first in vacuum environment with analysis of the intermolecular ‘intrinsic’ synthons in the bulk structure and the unsaturated ‘extrinsic’ synthons at the surface. Using grid based search methods the solvent interactions at the habit faces are then analysed with respect to their effect on crystal morphology.
PABA has two known forms α and β1. The α polymorph crystallises is a needle like morphology whereas the β forms plate like crystals. HABIT 982 uses atomistic forcefields to calculate the strength of the intermolecular interactions within the crystal using the atom-atom approximation in a matter of seconds. The important morphological faces selected using the BFDH rule states that the morphological important faces will have the largest interplanar distance but does not account for chemical bonding. The attachment energy term pioneered by Bennema3 et al takes into account the intermolecular forces within the crystal and is proportional to the growth rate of the faces and can also be calculated using HABIT for the user selected morphologically important habit faces using the following equations. In addition to calculating the attachment energy the bulk intermolecular forces can be calculated and compared to the interactions at the surface. The orientation of the molecules and dangling unsaturated functional groups as predicted by perfect termination of the crystal provide valuable information about the surface chemistry at the crystal faces and can therefore allow predictions of how solvent will interact at crystal surfaces and effect the crystal morphology.Further to the morphological prediction based on the internal structure in vacuum, solvent effects can be approximated using the grid based search SYSTSEARCH4 developed at the University of Leeds. A probe solvent molecule is allowed to move around the crystal surface along user set grid points and change orientation to find the most energetically favourable position at the crystal surface. The intermolecular interaction between the probe molecule and the surface is calculated using the same atomistic forcefields as HABIT 98 and the whole process is possible in a matter of minutes. The interaction between the surface and the probe molecule can then be used to calculate a modified attachment energy and therefore a solvent induced morphology prediction. Theoretical prediction of the morphology of PABA showed reasonable agreement using the attachment energy theory in HABIT. The intrinsic and extrinsic synthons were evaluated using HABIT. The SYSTSEARCH showed an improved prediction upon evaluation of the interactions at the surfaces and modified attachment energy. These results were also compared to other case studies undertaken within the group. References [1] Gracin, S.; Rasmuson, Å. C., Polymorphism and Crystallization of p-Aminobenzoic Acid. Crystal Growth & Design, 4 (2004) 1013-1023 [2] G. Clydesdale, R. Docherty, K.J. Roberts, HABIT - a program for predicting the morphology of molecular crystals, Computer Physics Communications, 64 (1991) 311-328. [3] P. Hartman, P. Bennema, The attachment energy as a habit controlling factor: I. Theoretical considerations, Journal of Crystal Growth, 49 (1980) 145-156. [4] R.B. Hammond, K. Pencheva, K.J. Roberts, Molecular modeling of crystal-crystal interactions between the alpha- and beta-polymorphic forms of L-glutamic acid using grid-based methods, Crystal Growth & Design, 7 (2007) 875-884. |
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Presentation: Oral at 17th International Conference on Crystal Growth and Epitaxy - ICCGE-17, General Session 1, by Ian RosbottomSee On-line Journal of 17th International Conference on Crystal Growth and Epitaxy - ICCGE-17 Submitted: 2013-04-15 17:51 Revised: 2013-07-22 14:52 |