Differential Optical Rotation for Chiral Analysis

用于手性分析的微分旋光度

• 批准号: 7275120
• 负责人: Phillip Ray Gibbs
• 金额: $ 38.26万
• 依托单位: STHENO CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275120
• 关键词: Differential; Optical; Rotation; Chiral; Analysis

DESCRIPTION (provided by applicant): Many diseases are still without an effective treatment today, and others have evolved resistances requiring new therapeutic agents to be developed. In the effort to develop discovery candidates for medical applications, an important observation is that the vast majority of useful drugs contain one or several chiral centers. Since the wrong enantiomer can cause harmful side effects, very high enantiomeric purity of therapeutics is essential for safe and effective treatment. Thus, both producing enantiomerically pure formulations and testing for enantiomeric purity are critical. Unfortunately, both of these activities remain significant challenges, even with the current "state of the art" analytical instrumentation. The proposed work intends to develop a next-generation chiral analytical technique that is suitable for non-contact, rapid, accurate, and highly sensitive screening of chiral samples. This approach utilizes several experimentally simple, but scientifically sophisticated techniques from "state of the art" optics research first developed for nonlinear-optical spectroscopy, but which we now apply to simple polarimetry. The method transforms the detection of optical rotation into a dual-beam technique that utilizes the advantages of differential signal detection. In addition, the Faraday effect is utilized using a sinusoidally varying magnetic field on the sample, optical-heterodyne detection by modulating the laser source, and double modulation phase-sensitive detection. The addition of optical heterodyning decreases the observed background noise in the system by moving the signals of interest to frequencies where electronic pickup and optical noise in the system do not contribute (analogous to double-beam-double-modulation detection in laser absorption spectrometry). By observing analytical signals in electronically quiet regions, additional electronic gain can be applied prior to the analog-to-digital converter further improving system sensitivity. We call this set of techniques and the resulting device the Magneto-Optical Phase Enantiomeric Detector-Optical Rotation (MOPED). In the effort to discover and develop pharmaceutical candidates, one must consider that the vast majority of useful drugs have two or more potential geometrical forms. As the wrong geometrical form can cause harmful side effects, very high purity of therapeutics is essential for safe and effective treatment. The proposed work intends to develop a next-generation analytical technique that is suitable for non-contact, rapid, accurate, and highly sensitive screening of chiral geometries.

描述（由申请人提供）：许多疾病今天仍然没有有效的治疗方法，其他疾病已经发展出耐药性，需要开发新的治疗剂。在开发用于医学应用的发现候选物的努力中，一个重要的观察结果是绝大多数有用的药物含有一个或多个手性中心。由于错误的对映体可能导致有害的副作用，因此非常高的对映体纯度的治疗剂对于安全有效的治疗是必不可少的。因此，制备对映体纯的制剂和测试对映体纯度都是至关重要的。不幸的是，这两项活动仍然是重大的挑战，即使与当前的“最先进的”分析仪器。本研究旨在开发新一代手性分析技术，适用于非接触、快速、准确和高灵敏度的手性样品筛选。这种方法利用了几个实验简单，但科学上复杂的技术，从“国家的最先进的”光学研究首先开发的非线性光学光谱，但我们现在适用于简单的偏振。该方法将旋光度的检测转化为利用差分信号检测的优点的双光束技术。此外，利用法拉第效应，使用正弦变化的磁场的样品，光外差检测调制激光源，和双调制相敏检测。光学外差的增加通过将感兴趣的信号移动到系统中的电子拾取和光学噪声不起作用的频率来降低系统中观察到的背景噪声（类似于激光吸收光谱法中的双光束双调制检测）。通过观察电子安静区域中的分析信号，可以在模数转换器之前施加额外的电子增益，进一步提高系统灵敏度。我们称这套技术和由此产生的设备的磁光相位对映体检测器旋光（MOPED）。在发现和开发药物候选物的努力中，必须考虑到绝大多数有用的药物具有两种或更多种潜在的几何形式。由于错误的几何形状会导致有害的副作用，因此非常高纯度的治疗剂对于安全有效的治疗至关重要。拟议的工作旨在开发下一代分析技术，适用于非接触，快速，准确和高灵敏度的手性几何形状筛选。