Molecules, Clusters and Crystals: A Multi-Scale Approach to Understanding Kinetic Pathways in Crystal Nucleation from Solution

晶体从溶液成核的过程需要溶质分子和溶剂分子分离，同时形成分子团簇，以产生新的纳米级相，该相随后可以生长成晶体。阐明控制这种成核过渡态结构的基本物理和化学仍然是物理科学中真正未解决的“重大挑战”之一。单个成核事件在空间上是局部的，但在分子振动的时间尺度上却很少发生，这使得实验检测和过程的分子建模都很困难。除此之外，现有的实验技术提供了时间和空间上的平均数据，因此只有通过实验和建模的结合才能获得对成核过程的见解。我们提出了一种新的方法来解决这个问题，我们在迄今为止前所未有的深度上仔细检查两个相关分子系统的结晶，建立在最先进的实验和计算技术的基础上，但首次将这些与原位同步辐射（SR） x射线散射和光谱方法结合起来，能够在分子分辨率上探测远距离和局部电子和几何结构。我们的假设是，通过利用适当的实验条件，应用这些最先进的时间分辨散射和光谱技术，并建立与所研究系统的宏观特征（晶体形态、多晶形态、溶液化学、晶体生长速率）一致的簇模型，我们可以从溶液平均结构随溶液过饱和度和时间增加的变化推导出成核事件的结构模型。因此，我们期望在成核过程的每一步都能得到深刻的结构信息：测量的分子尺度性质可以用来面对分子、超分子和固态水平的计算预测，从而揭示成核途径的结构和尺寸参数。因此，我们对这一科学领域的理解有望发生重大变化。

The process of crystal nucleation from solution requires, as its initial stage, separation of solute and solvent molecules and simultaneous formation of molecular clusters in order to create a new, nano scale, phase which can subsequently grow to become a crystal. Elucidating the fundamental physics and chemistry that govern the structure of this nucleation transition state remains one of the truly unresolved 'grand challenges' of the physical sciences. Individual nucleation events are localised in space but rather infrequent on the time-scale of a molecular vibration making both experimental detection and molecular modelling of the process difficult. In addition to this, available experimental techniques provide data averaged over both time and space so that extracting insights into the nucleation process may only be achieved through a combination of experiment and modelling. We propose a novel approach to this problem in which we scrutinise the crystallisation of two related molecular systems in hitherto unprecedented depth, building on established state-of-the-art experimental and computational techniques, but combining these, for the first time, with in situ synchrotron radiation (SR) X-ray scattering and spectroscopy methodologies capable of probing long range and local electronic and geometric structure at molecular resolution. Our hypothesis is that, by utilising appropriate experimental conditions, applying these state of the art time resolved scattering and spectroscopic techniques and building cluster models that are consistent with macroscopic features of the systems studied (crystal morphology, polymorphic form, solution chemistry, crystal growth rates), we can deduce a structural model of a nucleation event from the change in averaged solution structure as a function of increasing solution supersaturation and time. We thus expect incisive structural information for every step of the nucleation process: measured molecular scale properties can be used to confront computational predictions at molecular, supra-molecular and solid-state levels, so that the structural and size parameters for the nucleation pathway are revealed. A step change in our understanding of this area of science is thus expected.