Carbon-13 Magnetic Resonance - Methods and Theory

碳 13 磁共振 - 方法和理论

基本信息

批准号：
7760851
负责人：
David Morris Grant
金额：
$ 22.35万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-06-01 至 2011-08-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7760851
关键词：
Affect Antioxidants Attention Biological Biological Factors Biology Carbon Carcinogens Catechin Cell Nucleus Charge Chemicals Chemistry Chitin Chocolate Collection Complement Complex Computers Country Dactinomycin Data Detection Development Dimensions Electrostatics Evolution Exhibits Flavonoids Glucosamine Grant Health Hydrogen Bonding Isotopes Laboratories Liquid substance Magic Magnetic Resonance Magnetism Malignant Neoplasms Measurement Methods Modeling Molecular Molecular Conformation Molecular Weight Neutrons Nucleosides Paclitaxel Peptides Pharmaceutical Preparations Pharmacologic Substance Physiologic pulse Plants Polymers Positioning Attribute Powder Diffraction Powder dose form Process Property Protons Psychological Techniques Publishing Resolution Roentgen Rays Sampling Solid Solubility Structure Sum System Techniques Tigers Time Utah Work base computerized data processing density design flexibility improved interest intermolecular interaction neutrophil programs public health relevance quantum research study solid state nuclear magnetic resonance stereochemistry success theories three dimensional structure tool

项目摘要

DESCRIPTION (provided by applicant): The principal aim of this proposal is the development of basic methods and theory for using solid state nuclear magnetic resonance (SSNMR) techniques in relevant biomedical problems using the C-13 and N-15 magnetic isotopes. SSNMR is becoming an increasingly important tool in almost all branches of chemistry and biology. Theoretical computations tie experimental data to structure and allow the influence of hydrogen bonding, conformation and stereo-chemistry to be systematically evaluated through analysis of hypothetical model compounds. New HETCOR, INADEQUATE, FIREMAT, and TIGER methods will be used. As many biomolecules have very low solubility, SSNMR methods offer an important way to investigate these systems. This allows x-ray powder diffraction (XRPD) to be combined with SSNMR in obtaining lattice structure. While diffraction methods characterize long range microcrystalline lattice arrays, SSNMR focuses with greater accuracy on short range order especially when studying proton positions in powders. XRPD finds considerable success when Z = 1 and when the molecular weight is not overly high. If Z e 2, the Rietveld structural fit of diffraction histograms tends to break down without independent information such as SSNMR initial structures. Thus, we intend to study a number of important bio-systems: flavenoids such as catechin (Z =2), Taxol. (Z =2x1/2). Actinomycin D has a doubling of two half molecules, The available single crystal structures for actinomycin D take advantage of the known lattice structure to aid in developing methods for the combined use of SSNMR and XRPD in powders. Catechin (powerful anti-oxidant) found in chocolate and the recently developed, stable Taxol. polymorph have never been obtained in single crystal form. Taxol. is one of the leading anti-carcinogen agents used to treat many different forms of cancer in our country at the present time, Structural information on Taxol. and its tubuline peptide could be of great health consequence. The N-15 applications include natural products, pharmaceuticals, nucleosides, peptides and related derivatives, etc. SSNMR is also proving to give reliable information on antioxidants from polyphenolic flavenoids. PUBLIC HEALTH RELEVANCE: We are using solid state NMR methods to study structure of biomedical systems that can be studied in no other manner. When combined with additional quantum chemical calculations, X-ray (both single crystal and microcrystalline powders approaches), density measurements, etc. structural information is obtained that can be gained in no other manner. Modern Biomedical work has become very dependent upon this type of data. Our focus is on new and powerful techniques. The applications include drug and pharmaceutical agents, several antioxidant flavonoids. Specifically, we have made considerable progress in the structure of Taxol., catechin, and a variety of new bioactive and potential drugs from plants, and chitisan, chitin which are derivatives of the very common natural polymer: glucosamine.

描述（由申请人提供）：该提案的主要目的是使用C-13和N-15磁同位素在相关的生物医学问题中使用固态核磁共振（SSNMR）技术的基本方法和理论的发展。 SSNMR几乎在化学和生物学的几乎所有分支中都变得越来越重要。理论计算将实验数据与结构联系起来，并允许通过分析假设模型化合物的分析来系统地评估氢键，构象和立体化学的影响。将使用新的Hetcor，不充分的，Firemat和Tiger方法。由于许多生物分子的溶解度非常低，因此SSNMR方法提供了研究这些系统的重要方法。这允许在获得晶格结构中将X射线粉末衍射（XRPD）与SSNMR结合使用。尽管衍射方法表征了远距离微晶晶格阵列，但SSNMR的精度更高，尤其是在研究粉末中的质子位置时。当z = 1且分子量不高时，XRPD会发现相当大的成功。如果Z E 2，则衍射直方图的Rietveld结构拟合往往会分解而没有独立信息，例如SSNMR初始结构。因此，我们打算研究许多重要的生物系统：类黄酮（例如儿茶素（Z = 2），紫杉醇）。（z = 2x1/2）。放线霉素D具有两个半分子的两倍，放线菌素D的可用单晶结构利用已知的晶格结构，有助于开发粉末中SSNMR和XRPD的合并使用方法。在巧克力和最近开发的稳定紫杉醇中发现的儿茶素（强大的抗氧化剂）。从未以单晶形式获得多晶型物。紫杉醇。是目前用于治疗我们国家多种不同形式的癌症的领先抗癌药物之一，有关紫杉醇的结构信息。它的小管肽可能会带来很大的健康后果。 N-15的应用包括天然产物，药物，核苷，肽和相关衍生物等。SSNMR也被证明可以提供有关多酚类黄酮的抗氧化剂的可靠信息。公共卫生相关性：我们正在使用固态NMR方法来研究无法以其他方式研究的生物医学系统的结构。当与其他量子化学计算结合使用时，X射线（单晶和微晶粉末方法），密度测量等。可获得无法以其他方式获得的结构信息。现代生物医学工作已经非常依赖这种数据。我们的重点是新的强大技术。应用包括药物和药物，几种抗氧化剂类黄酮。具体而言，我们在紫杉醇，儿茶素的结构以及植物的各种生物活性和潜在药物的结构上取得了长足的进步，而chitisan，chitin是非常常见的天然聚合物的衍生物：葡萄糖胺。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structure elucidation of three triterpenoid saponins from Alphitonia zizyphoides using 2D NMR techniques.

使用 2D NMR 技术解析 Alphitonia zizyphoides 中的三种三萜皂苷的结构。

DOI：
10.1021/np50104a004
发表时间：
1994
期刊：
Journal of natural products
影响因子：
5.1
作者：
Li,D;Owen,NL;Perera,P;Andersson,C;Bohlin,L;Cox,PA;Pugmire,RJ;Mayne,CL;Grant,DM
通讯作者：
Grant,DM

Improvements in the computerized analysis of 2D INADEQUATE spectra.

二维不充分光谱的计算机分析的改进。