Quantitative scale for halogen bonding and hydrogen bonding: a foundation for self-assembly

该项目将提供分子间相互作用的定量实验数据，为未来的自组装研究奠定基础。分子间相互作用中最突出的一类是氢键。最近建立的是卤素键，一种与氢键平行的非常重要的相互作用。分子内的原子通常通过强大的化学键（150-1000千焦/摩尔）结合在一起，但它们的分子结构通常受到大约弱10倍的力的强烈影响，其中最著名的是氢键。正是氢键为DNA编码遗传信息和蛋白质获得特异性提供了途径。这些较弱的力也是分子间相互作用的基础，因此决定了小分子如何组装成更大的结构。自组装是形成更大结构的过程：它遍及从材料化学到催化再到结构生物学等领域的研究和技术。例如，药物与蛋白质的相互作用决定了其活性，催化剂与底物的相互作用决定了其特异性。当形成强化学键时，例如在氮原子和氢原子之间，电子分布不均匀；氮得到一个轻微的负电荷，氢得到一个轻微的正电荷。当一个带轻微正电荷的氢原子与另一个带轻微负电荷的原子相互作用时，就形成了氢键：例如N-H…OC，其中O带部分负电荷。在这个项目中，我们还将关注卤素键，其中氢的作用被带部分正电荷的卤素（碘、溴或氯）取代。当这些卤素与其他基团连接时，就会出现这种情况，这些基团会把电子吸走，例如含氟基团。2004年，Hunter提出了一种定量方法来理解分子相互作用的影响，该方法统一了所有溶剂中所有类别的分子间相互作用。基本原理现在已经在形成氢键的简单系统中得到了实验验证，但挑战是在更复杂的系统中实施这种方法，并具有不同类型的分子间相互作用。该研究计划将检查氢键过渡金属配合物和卤素键一般。由此产生的定量测量将与现有的有机氢键知识放在一个共同的尺度上。用于定量探测溶液中分子相互作用的主要技术将是核磁共振波谱（尤其适用于过渡金属化合物）和自动紫外/可见波谱（尤其适用于有机分子）。相互作用能通常在许多温度下确定，给出了全范围的能量信息。相互作用的几何结构将由固态核磁共振支持的x射线晶体学进行研究。实验研究将以量子力学计算方法为基础，可以预测相互作用的位置和强度。brammer - hunt - perutz团队带来了研究分子间相互作用的丰富经验和已建立的合作记录。该项目分为三个部分：(A)过渡金属化合物的研究，(B)有机分子相互作用的研究，(C)氢键和卤素键供体和受体强度的定量尺度的开发。Brammer在晶体学方面处于领先地位，Perutz在核磁共振光谱（特别是过渡金属配合物）方面处于领先地位，Hunter在有机分子的自动紫外/可见光谱方面处于领先地位。Hunter也是数据分析方法和计算方法的领导者。

This project will provide quantitative experimental data on interactions between molecules that will underpin future research in self-assembly. The pre-eminent class of intermolecular interaction is the hydrogen bond. More recently established are halogen bonds, highly important interactions which parallel hydrogen bonds. The atoms within molecules are usually held together by strong chemical bonds (150-1000 kJ/mol), but their molecular structures are often strongly influenced by forces that are about 10 times weaker, of which the most famous is the hydrogen bond. It is the hydrogen bond that provides the means for DNA to encode genetic information and for proteins to acquire their specificity. These weaker forces also underlie interactions between molecules, and hence determine how small molecules assemble into larger structures. Self-assembly is the process of forming the larger structures: it pervades research and technology in areas ranging from materials chemistry to catalysis to structural biology. For instance, it is the interaction of a drug with a protein that determines its activity, or the interaction of a catalyst with a substrate that determines its specificity.When strong chemical bonds are formed, for instance between nitrogen and hydrogen atoms, the electrons are distributed unevenly; the nitrogen acquires a slight negative charge and the hydrogen acquires a slight positive charge. A hydrogen bond is formed when a hydrogen atom with a slight positive charge interacts with another atom with a slight negative charge: e.g. N-H...OC, where O has a partial negative charge. In this project we will also focus on the halogen bond, in which the role of the hydrogen is replaced by a halogen (iodine, bromine or chlorine) with the partial positive charge. This situation arises when these halogens are attached to other groups that pull the electrons away, for instance fluorine-containing groups. In 2004, Hunter presented a quantitative approach to understanding the impact of molecular interactions that has unified all classes of intermolecular interaction in all solvents. The basic principles have now been experimentally validated for simple systems that form hydrogen bonds, but the challenge is to implement this approach in systems that are more complicated and feature different types of intermolecular interaction. The research programme will examine hydrogen bonds to transition metal complexes and halogen bonds in general. The resulting quantitative measurements will be placed on a common scale with existing knowledge of organic hydrogen bonds.The dominant techniques for quantitative probing of molecular interactions in solution will be nuclear magnetic resonance spectroscopy (especially appropriate to the transition metal compounds) and automated ultraviolet/visible spectroscopy (especially for the organic molecules). The interaction energies will often be determined at many temperatures, giving a full range of energetic information. The geometry of the interactions will be studied by X-ray crystallography, supported by solid-state nuclear magnetic resonance. The experimental studies will be underpinned by computational methods based on quantum mechanics that can predict the site of interaction and its strength. The Brammer-Hunter-Perutz team bring great experience of studying intermolecular interactions and an established record of collaboration. The project is divided into three sections: (A) studies of transition metal compounds, (B) studies of interactions of organic molecules, (C) development of quantitative scales for hydrogen-bond and halogen-bond donor and acceptor strengths. Brammer provides the lead in crystallography, Perutz in NMR spectroscopy especially of transition metal complexes, and Hunter in automated UV/visible spectroscopy of organic molecules. Hunter also is the leader in data analysis methods and in computational methods.