New Chemistry from Biology with Bioinorganic Chemistry

尽管化学生物学有许多动机和定义，但推动我的实验室研究计划的一个因素是，它是一个“发现新化学”的主题和方法。我们统一的指导假设是全球性的、开放式的、令人振奋的；通过了解生物进化是如何绕过地球温度、压力、环境和元素分布所施加的基本化学限制的，可以发现相当多的新化学。这种方法允许发现和创新，因为不仅使用和开发了新技术和工具，以帮助解决重要的健康相关问题，而且还发现了更深层次科学问题的解决方案。目前Bohle小组的化学生物学研究遵循三个一般主题：A；第一个与寄生虫经常使用的不寻常的生物化学有关，与疟原虫（疟疾）B等病原体的血红素代谢有关；生物无机化学中很少利用的元素，如砷、钨和C；最后以生物启发氮化学为研究领域。答：像疟原虫这样的寄生虫具有高度进化的生物学，这使得它们具有一些最复杂的生命周期，并且通常具有优雅的生物化学。它们通常有复杂的手段来绕过宿主的免疫系统；它们是应用化学生物学思想的合乎逻辑的地方。未充分利用元素的生物化学仍然是化学生物学的一个具有挑战性的领域。事实上，像钨和砷这样的元素是相对常见和可用的，但进化很少在任何情况下使用它们中的任何一种。我们对这些主题的研究是高度合作的，目前主要集中在它们的毒理学和药用价值上。最后，很少有第一行元素具有氮及其氧化物的显著变化的氧化态化学。如果我们能够理解氮氧化物是如何在生物体中被利用的，原则上我们就可以在商业/工业环境中使用这些想法，特别是在减少污染的策略中。

Although there are many motivations and definitions of chemical biology the one that drives the program of research in my laboratory is that it is a theme and an approach "to discover new chemistry." Our unifying guiding hypothesis is global, open-ended, and invigorating; by understanding how biological evolution has circumvented the fundamental chemical limitations imposed by terrestrial temperature, pressure, environment, and element distribution considerable new chemistry can be discovered. This approach allows for discovery and innovation in that not only are new techniques and tools used, and developed, to help solve important health related problems, but solutions to deeper scientific issues are uncovered. Current chemical biology research in the Bohle group follows three general themes: A; the first is related the unusual biochemistry often employed by parasites, with the heme metabolism in pathogens such as plasmodia (malaria), B; the bioinorganic chemistry of rarely utilized elements such as arsenic and tungsten, and C; the final area to the study of bio-inspired nitrogen chemistry. A. Parasites such as plasmodia have a highly evolved biology which allows them to have some of the most complicated life cycles and often have elegant biochemistry. Often they have sophisticated means to circumvent the host's immune system; they are a logical place to apply the ideas of chemical biology. B. The biochemistry of underutilized elements remains a challenging area of chemical biology. Elements such as tungsten and arsenic are in fact relatively common and available, and yet evolution has rarely used either of them in any context. Our research into these topics is highly collaborative and at present focusses on their toxicology and medicinal value. Finally C, few first row elements have the remarkably variable oxidation state chemistry of nitrogen and its oxides. If we can understand how the nitrogen oxides are employed in organisms we can in principle use these ideas in commercial/industrial settings especially for pollution abatement strategies. Our approach to this research is to work on the fundamental problems in each of these themes. This style is ideally suited for the training of HQP and it does not tie us to a particular technique, method, or class of compounds. To illustrate this diversity my group can frequently be found working at Synchrotrons as well as preparing and characterizing new compounds. For the latter we use a wide range of spectroscopic and structural techniques, with X-ray diffraction being particularly useful. Theoretical methods are also drawn upon for both their predictive and supporting roles. At its best our work is highly collaborative with our chemistry having value for biologists and clinicians as well stimulating our efforts in bioinorganic chemical biology.