Bioinorganic chemistry of metalloproteins and synthetic analogues

将开展的研究涉及金属及其宿主分子的生物功能，以及合成类似物的技术应用性质的预测。生物系统中的金属控制着所有的生命，在许多情况下是通过与蛋白质多肽链中氨基酸的供体原子结合来控制的。金属离子还与特定的螯合剂结合，然后激活蛋白质发挥功能。金属是催化的活性部位，维持细胞离子强度，形成结构材料，通过与氨基酸配位控制蛋白质折叠。虽然所有的生物都需要各种金属，但这些金属离子的供应和可用性必须在细胞内进行调节，以避免缺乏，从而导致功能压力，而过量则会导致毒性。*我们的计划有三个长期目标。首先，了解蛋白质金属硫蛋白在锌和铜的代谢途径中的作用，以及金属硫蛋白在金属类药物进入细胞时作为“细胞守门人”的作用。第二，详细描述在一系列革兰氏阴性和革兰氏阳性致病菌中，血红素获取和转移的迷人复杂过程是如何工作的。细菌需要铁，但对于人类致病菌来说，宿主环境几乎没有游离铁。因此，这些微生物采用了多种策略来寻找铁。人体内的一种方法是将含铁的血红素从血红蛋白中剥离出来，并将其整个输送到细菌细胞内部，在那里提取铁。当一个完整的血红素穿过细胞壁并穿过细胞膜时，这个系统涉及到蛋白质到蛋白质的交接。第三，根据理论得到的电子结构确定卟啉类化合物的光学性质和氧化还原性质的几何控制。这项工作涉及到卟啉及其类似物壮观的光学性质和氧化还原性质。卟啉通过镁的叶绿素以及许多基于卟啉的蛋白质对植物生命起作用。这些生物特性可以通过技术加以利用，但大自然已经有30亿年的时间来提炼化学物质。修饰后的卟啉很难合成，只有到那时才知道它们的光光和氧化还原性质。通过在合成前预测分子结构的性质而产生的生产率提高将导致更快的商业开发。计划中的研究利用通常用于这些基于金属的研究的光谱技术(光学吸收和发射、磁性圆二色、基于金属的核磁共振和基于同步加速器的EXAFS)来了解使用电喷雾电离光谱发现的反应性。**

The research to be carried out concerns the biological functionality of metals and their host molecules, and the prediction of properties for technological applications of synthetic analogues. Metals in biological systems control all life, in many cases by binding to the donor atoms of amino acids in the peptide chains of proteins. Metal ions also bind to specific chelators that then activate proteins for function. Metals are the active site for catalysis, maintain cellular ionic strength, form structural materials and control protein folding through their coordination to amino acids. While all organisms require a variety of metals, the supply and availability of these metal ions must be regulated in the cell to avoid deficiency, leading to functional stress, while an excess leads to toxicity.***Our program has three long term goals. First, to understand the role of the protein metallothionein in the metabolic pathways of zinc and copper, and also the role of metallothionein as a `cellular gate-keeper' deactivating metal-based drugs as they enter the cell. Second, to describe in detail how the fascinatingly complicated process of heme acquisition and transfer works in a range of gram-negative and gram-positive pathogenic bacteria. Bacteria require iron but for human pathogenic bacteria the host environment is almost devoid of free iron. These microbes thus employ a combination of strategies to scavenge for iron. One method in the human host is to rip the iron-containing heme out of hemoglobin and transport it whole to the inside of the bacterium cell where the iron is extracted. This system involves protein to protein handovers of a complete heme, as it is moves across the cell wall and through the cell membrane. Third, to determine the geometrical control of the optical and redox properties of porphyrinoids from theoretically-obtained electronic structures. This work concerns the spectacular optical and redox properties of porphyrins and their analogs. Porphyrins are responsible for plant life through the magnesium chlorophyll, and as well many porphyrin-based proteins. These biological properties can be exploited technologically but Nature has had 3 billion years to refine the chemistry. Modified porphyrins are hard to synthesize and their photo-optic and redox properties become known only then. The productivity enhancements arising from predictions of the properties of molecular structures prior to synthesis will lead to faster commercial exploitation. The planned research utilizes the spectroscopic techniques typically used for these metal-based studies (optical absorption and emission, magnetic circular dichroism, metal-based NMR, and synchrotron-based EXAFS) to understand reactivities discovered using electrospray ionization spectrometry.**