在本页:
地中海实验室
Chemical Synthesis, Bioinorganic Chemistry and Polymer Chemistry
教授: 克里斯蒂娜·库利博士.D.
概述:
库利实验室的研究应用合成有机化学的力量来解决生物学和人类健康方面的问题. 我实验室的学生将有机会设计和合成新分子，并在以下两个主要项目领域评估其检测和治疗人类疾病的能力.
我们的主要研究领域是开发新的方法来放大分子信号，作为一种检测生物分子相互作用和潜在作用的方法, 疾病. We have developed fluorogenic monomers that are not fluorescent in monomer form, but glow when incorporated into a polymer synthesized by various methods, 例如原子转移自由基聚合(ATRP). Polymer fluorescence is quantifiable by fluorescence readers or visible to the naked eye, and tracks with the concentration of polymerization initiator, 哪个服务于模型分析人员.
这个荧光聚合亚群目前有许多研究方向，从基本的有机合成和聚合研究到检测应用. 目前的项目旨在合成新的单体，以改善物理性质，如水溶性, development and evaluation of alternative light-initiated fluorogenic polymerization platforms, optimization of the fluorogenic polymerization approaches for analyte detection, and application to the direct detection of proteins and biomolecular interactions. 在这个领域工作的学生将应用一系列有机, 高分子与生化技术, 从化学合成小分子和自由基聚合技术引发的各种方法，从金属催化剂到可见光照射, to analysis and characterization of the polymers formed by gel permeation chromatography, 核磁共振波谱学, 荧光分析方法.
The Cooley lab has a second subgroup in the general field of therapeutic drug delivery, 利用活性氧(ROS)的感知在病变组织中进行前药激活和治疗释放. 前药是药物的“笼子”版本，在特定的生物条件下释放到游离药物之前是无活性的. 我们合成并评价了AA 147的前药, 在再灌注事件(如心脏病发作和中风)后，哪一种激活应激反应信号通路作为治疗靶点. These prodrugs of AA 147 are selectively uncaged by the presence of reactive oxygen species (ROS), 哪些在再灌注事件中高水平发生. 我们也在探索其他类型的可释放的AA 147前药，以改善体内动物研究的药效学特性, and the synthesis of fluorogenic ROS sensors for collaborative chemical applications. Students in this area will gain experience with small-molecule synthesis and characterization, and analyze their therapeutic release profile under biological conditions.
兰伯特实验室
有机化学
Amber is the fossilized end product of resinous materials exuded by plants millions of years ago. 除了南极洲，它在每个大陆都有. 琥珀至少有五种化学性质不同的类型, depending on the botanical material from which the original exudate came from. 核磁共振(NMR)光谱可以区分这些不同的植物来源，并为确定琥珀的真伪和了解其地理来源提供了一种手段.
更一般的, exudates are complex mixtures of organic compounds produced by plants, 通常是受伤或疾病的结果. Secreted as liquids, exudates may harden to solids in hours to months on the surface of the plant. These materials have found numerous practical applications throughout human history, and they provide a molecular window to the classification of plants (taxonomy). 我们已经发现，在同一种植物和同一种植物之间，渗出物的分子结构是非常强健和一致的. There are several, distinct chemical constitutions of exudates. Resins, which can form amber through fossilization, are composed of terpenoid compounds. 树胶是由多糖构成的. Gum resins like frankincense and myrrh contain both materials. 基诺含有酚类物质. 虽然这四个化学基团是最大的, 还有其他几个较小但不同的化学基团.
We are carrying out a worldwide survey of plant exudates from all plant families, 还有琥珀, necessitating field acquisition of materials and analysis by NMR in the lab. 我们也在研究热对琥珀及其稍微年轻一些的同类分子结构的影响, 柯巴脂. Heat has been used to alter the properties of amber prior to carving. Spectroscopic examination of artificially heated samples may clarify how structure change with heating.
希勒实验室
Bioinorganic Chemistry; Computational Chemistry; X-ray Spectroscopy
类型: 无机化学
教授: Jason Scherer博士.D.
希勒集团的研究主要集中在了解与生物和工业相关的过渡金属物种的电子结构如何影响其反应性和物理性质. Central to our work is the synergistic use of synthetic, spectroscopic and computational chemistry. Although we perform some work with naturally occurring biological systems or industrial catalysts, we primarily study synthetic mimics of these systems to probe a specific aspect of their chemistry. Briefly outlined below are two projects currently being undertaken by the 希勒集团.
1. 探测含镍超氧化物歧化酶. 含镍超氧化物歧化酶(NiSOD)利用NiII/NiIII氧化还原对催化剧毒超氧化物(O2 -)转化为二氧和过氧化氢. 在还原的NiII氧化态中，镍位包含在扭曲的方形平面NiN2S2配位环境中，配位体来源于Cys2, Cys6, the N-terminal amine nitrogen and an amidate nitrogen from Cys2. 我们一直在探索的NiSOD活性位点的一个不寻常的特征是，其中一个配位的Cys硫配体是质子化的, 形成Ni-S(H+)-Cys基团. A number of roles for this moiety can be envisioned; our hypothesis is that protonation of the Cys sulfur ligand poises the nickel site for reactivity. 我们假设质子化提高了以镍为主的轨道的能量，允许电子从NiII转移到O2 -, 从而产生O22 -(过氧化物)和NiIII. 为了验证这个假设, 我们正在制备一些基于金属肽的NiSOD模拟物以及可以支持可逆Ni-S(H+)-Cys形成的小过渡金属配合物. By spectroscopically examining the influence of sulfur protonation in such mimics, we seek to understand the role(s) of the Ni-S(H+)-Cys moiety in NiSOD reactivity, 和一般含Ni-S-R的化合物.
2. Understanding Transition Metal Ligand Bonds Through the Lens of Valence Bond Theory. 在现代化学物理中，化学键的量子力学描述主要通过三个模型来描述:分子轨道, 密度泛函, 和价键(VB)理论. All of these approaches have distinct benefits and disadvantages. VB theory has the advantage of placing bonding in terms that chemists understand (covalent vs ionic bonding), 这就产生了对化学键的直观描述. 然而, 只是在过去的十年里，VB理论方法才发展到可以在足够高的理论水平上处理更大的化学系统，从而产生准确的解决方案. We have taken advantage of these recent advances in VB theory to explore the bonding, 能量, and reactivity of transition metal complexes involved in organometallic transformations. 例如, 我们最近研究了[CuR4] -配合物(R =烷基)的还原消除，并发现了一些关于这类物质的化学“隐藏”特征. 例如, one surprising aspect of such reactions is that they are not reductive eliminations in any physically meaningful sense of the word; instead they can be viewed as admixtures of radical C-C couplings and simple Lewis acid/base reactions.
Urbach集团
Supramolecular Chemistry; Biosensing; Diagnostics; Drug Formulation
网站: Urbach集团
教授: 亚当·厄巴赫博士.D.
药物化学和医学诊断的目的是在复杂的混合物中识别特定的蛋白质, 比如血, 然后粘在蛋白质上. 药物阻断了这种蛋白质的正常功能. 医学诊断测量的是这种蛋白质的数量. The Urbach lab develops new chemistry for the recognition of specific proteins, and we use this chemistry to solve important biomedical problems. Students are involved in experimental design and implementation, 解决问题, 数据分析, 演讲, 和出版.
Students in the Urbach research group learn a range of techniques, 其中包括有机合成来制造多肽, 物领域, 水凝胶, and modified proteins; NMR spectroscopy; mass spectrometry; microcalorimetry; fluorescence spectroscopy; circular dichroism spectroscopy; and X-ray crystallography. 这种方法和途径的结合为学生提供了广泛的技术和深度的研究，为进一步学习有机化学奠定了良好的基础, 生物物理化学, 药物化学, 生物化学, 生物工程, 和生物技术.
目前的项目包括:1)开发新的化学方法来识别蛋白质和蛋白质的氨基酸序列. Our discoveries have established new rules for predictive protein recognition, and we are currently working to expand the range of proteins that are accessible by our compounds, 并增加相互作用的强度和选择性. 2)合成具有新性质的新蛋白受体. 3) Developing technology for the quality control of protein drug formulations. 4) Developing a new strategy for protein drug formulation that enables controlled time release. Dr. Urbach is always interested in discussing new ideas with students. These projects are funded by grants from the National Institutes of Health and the Welch Foundation.