Institute of Process Engineering, ETH Zurich, CH-8092 Zurich, Switzerland.
J Am Chem Soc. 2012 Oct 17;134(41):17221-33. doi: 10.1021/ja307408x. Epub 2012 Oct 4.
Controlling the shape of crystals is of great practical relevance in fields like pharmacology and fine chemistry. Here we examine the paradigmatic case of urea which is known to crystallize from water with a needle-like morphology. To prevent this undesired effect, inhibitors that selectively favor or discourage the growth of specific crystal faces can be used. In urea the most relevant faces are the {001} and the {110} which are known to grow fast and slow, respectively. The relevant growth speed difference between these two crystal faces is responsible for the needle-like structure of crystals grown in water solution. To prevent this effect, additives are used to slow down the growth of one face relative to another, thus controlling the shape of the crystal. We study the growth of fast {001} and slow {110} faces in water solution and the effect of shape controlling inhibitors like biuret. Extensive sampling through molecular dynamics simulations provides a microscopic picture of the growth mechanism and of the role of the additives. We find a continuous growth mechanism on the {001} face, while the slow growing {110} face evolves through a birth and spread process, in which the rate-determining step is the formation on the surface of a two-dimensional crystalline nucleus. On the {001} face, growth inhibitors like biuret compete with urea for the adsorption on surface lattice sites; on the {110} face instead additives cannot interact specifically with surface sites and play a marginal sterical hindrance of the crystal growth. The free energies of adsorption of additives and urea are evaluated with advanced simulation methods (well-tempered metadynamics) allowing a microscopic understanding of the selective effect of additives. Based on this case study, general principles for the understanding of the anisotropic growth of molecular crystals from solutions are laid out. Our work is a step toward a rational development of novel shape-affecting additives.
控制晶体的形状在药理学和精细化学等领域具有重要的实际意义。在这里，我们研究了一个典型的例子，即尿素，它从水中结晶时具有针状形态。为了防止这种不理想的效果，可以使用抑制剂来选择性地促进或阻碍特定晶面的生长。在尿素中，最相关的晶面是{001}和{110}，它们分别以较快和较慢的速度生长。这两个晶面的生长速度差异是导致在水溶液中生长的晶体具有针状结构的原因。为了防止这种效果，可以使用添加剂来减缓一个晶面相对于另一个晶面的生长速度，从而控制晶体的形状。我们研究了在水溶液中快速{001}和慢速{110}晶面的生长以及像缩二脲这样的形状控制抑制剂的作用。通过分子动力学模拟进行广泛的采样，提供了生长机制和添加剂作用的微观图景。我们发现{001}晶面的生长是连续的，而慢速生长的{110}晶面则通过一个诞生和扩展过程演化，其中决定速率的步骤是在二维晶核表面形成。在{001}晶面，生长抑制剂如缩二脲与尿素竞争表面晶格位置的吸附；而在{110}晶面，添加剂不能与表面位置特异性相互作用，只能起到对晶体生长的轻微空间位阻作用。通过先进的模拟方法（调谐的元动力学）评估添加剂和尿素的吸附自由能，从而可以从微观上理解添加剂的选择性作用。基于这个案例研究，为理解从溶液中各向异性生长的分子晶体奠定了一般原理。我们的工作是朝着合理开发新型形状影响添加剂迈出的一步。
