Growth Of L-alanine Crystals In Aqueous Solution:a Molecular Modeling Study

Crystallization is widely used in chemical industriy because of its high efficiency, low energy cost, mild operating condition and high product quality. Crystallization is also frequently encountered in research in the field of physics, chemistry, materials and life science. Solution crystallization, which is the mostly used, involves sophisticated nucleation and growth phenomena and is affected by many factors. For an optimal design of the crystallization process for controlled product quality in terms of purity, polymorph and morphology, a fundamental understanding of crystal growth mechanism and how these factors, especially the solvent and impurity, relate to each other and affect the crystallization process is critical. So far, great efforts have been made and a number of models proposed to investigate the solvent and impurity effects on crystal growth, but few of them have gained broad acceptability, and the picture about the interaction between host and guest molecules during crystal growth is still vague. In this work, crystal growth of L-alanine in the presence of solvent and impurity is studied by combining experiment and molecular simulation for an molecular level understanding of the effects of solvent and impurity on crystal growth.In aqueous solution crystallization, solvent exerts great impact on L-alanine crystal growth because of the strong hydrogen bonded interactions between the hydrophilic groups of L-alanine molecules and H2O molecules. Solvent effects both on the structure of crystal interfaces and on the self-association of solute molecules are investigated employing MD simulation. A solvated interface model is proposed and extensively analyzed, from thermodynamics and kinetics, to estimate the modification of surface structure and the energy barrier of solute adsorption induced by H2O. Through MD simulations of the structure of L-alanine in solvent boxes, the potential growth units of L-alanine in aqueous solution are determined, and their evolution is derived by analyzing their effective solvent layers.On the basis, the impurity effects of L-valine, which is structurally related to L-alanine, on crystal growth of L-alanine are studied. The experimental results show that when the impurity concentration is low, the crystal growth of L-alanine tends to be retarded with different mechanisms on different surfaces, however, when the impurity concentration is higher, the crystal growth of the end surface of L-alanine is surprisingly promoted. To understand the phenomena, MD simulations of solute adsorption on both non-solvated and solvated crystal interfaces in presence of impurity are performed. An intrinsic impurity effectiveness factor is proposed by taking into consideration the competitive adsorption, at either step or terrace, between the solute and the impurity, and the competitive adsorption of the impurity between step and terrace. It rationally illuminates the different inhibition effects of L-valine on different crystal surfaces. Furthermore, according to the calculation of the influences of the impurity and solvent on the surface diffusion of solute molecules, the coupling effect of impurity and solvent on crystal growth is uncovered. L-valine executes promotion effect by approaching L-alanine molecules to eliminate the negative effect of H2O on solute surface diffusion.The main achievements in the thesis are as follows:1) The predicted habits of L-alanine using BFDH and AE methods vary a lot from the solution grown habit, indicating a great influence of solvent on crystal growth. The solvated interface model reveals that the crystal growth is affected by the density of effective solute (ρhkl) at interfaces and the energy barrier of solute adsorption (△ESI). From thermodynamics, the density of effective solute is smaller at the end surface than the side surfaces, leading to a steady crystal growth of the end surface during a large concentration range. From kinetics, the energy barrier of solute adsorption is much lower at the end surface, resulting in a fast crystal growth of the end surface. Combine thermodynamics with kinetics, the crystal morphology derived from molecular simulation agrees well with the experimental result.2) MD simulation of the self-association of solute molecules in solvent boxes reveals that the growth units of L-alanine in aqueous solution are dominated by monomers and dimers. Based on the analysis of the effective solvent layer of the two growth units, it can be deduced that L-alanine mainly exists as dimers when the supersaturation is low, and the monomers when the supersaturation is high. This forecasts a sudden increase in the crystal growth rate, which is verified by studying the growth of L-alanine (011) surface at different supcrsaturations using the single crystal growth experiments.3) Single crystal growth experiments with the presence of impurity show that L-valinc has different effects on different surfaces of L-alaninc. The growth of the (011) surface is retarded but not totally blocked by L-valine, while the growth of the (120) surface is almost completely inhibited even with a lower impurity concentration. Through molecular simulation, the competitive adsorption, at either step or terrace, between the solute and the impurity, and the competitive adsorption of the impurity between steps and terraces are evaluated and the impurity effect is attributed to an intrinsic impurity effectiveness factor ehkl.The impurity effectiveness on the (120) surface is larger, indicating a strong adsorption-inhibition effect, while the impurity effectiveness on the (120) surface is lower, indicating a higher immigration tendency of L-valine, which may recover the growth to a certain degree. This provides a rational explanation of different impurity effects of L-valine on different crystal surfaces of L-alanine.4) Molecular simulations of L-alanine and L-valine adsorption on the non-solvated and solvated interfaces show that H2O limits the surface diffusion of L-alanine by forming hydrogen bonds with it, and L-valine has no influence on the surface diffusion of L-alanine. Therefore, L-valine frees L-alanine from the confinement of H2O by approaching L-alanine molecules to repel H2O around them, and eventually promotes the crystal growth.5) Combining the adsorption-inhibition and the diffusion-promotion effects of L-valine, we can conclude that when the impurity concentration is lower, the average distance between L-valine and L-alanine is too large to repel the adsorbed H2O of L-alanine, and the adsorption-inhibition effect is of priority. When the impurity concentration is higher, the average distance is small enough to repel the adsorbed H2O of L-alanine, and the diffusion-promotion effect dominates the impurity effect. Overall, an unusual promotion effect of L-valine on L-alanine crystal growth, after an initial inhibition effect, is anticipated.