Novel Extended Red-Shifted Xanthene Dyes

说明(申请人提供)：在电磁光谱的长可见/近红外(NIR)区域工作的荧光染料是体内靶向分子探针、荧光配体、酶底物和一般示踪剂的优秀报告组件。这类染料目前供不应求，那些商业上可以获得的染料非常昂贵，或者只有在严格限制的许可协议下才能获得。许多现有的染料具有不受欢迎的性质，如相对较高的非特异性结合和聚集的倾向，部分原因是合成方法不优化和分子设计不充分，导致价格昂贵。这项工作的主要重点是发现新型的长波长近红外染料，用于生物医学体内成像、高通量筛选和其他应用技术，如免疫荧光显微镜、荧光共振能量转移和荧光激活细胞分选和计数。影像技术的发展对临床医学产生了深远的影响，包括超声扫描、磁共振成像、X射线计算机断层成像和核断层成像。这些系统主要用于显示解剖、生理和代谢参数，但它们越来越多地被用于实验动物系统，用于体内细胞和分子水平的成像。这些当前使用的成像系统依赖于物理参数和属性来产生图像对比度，例如声阻抗、电磁波阻抗或核对准。活体荧光成像提供了更灵敏的肿瘤早期检测，这是现有成像技术很难实现的。将开发新的合成化学途径，使高纯度染料能够进行克级合成，并将产生更广泛地供研究和科学界使用的产品。

DESCRIPTION (provided by applicant): Fluorescent dyes that operate in the long visible / near infra-red (NIR) region of the electromagnetic spectrum are excellent reporter components of in vivo targeting molecular probes, fluorescent ligands, enzyme substrates and general tracers. Such dyes are in very short supply at the present time and those that are commercially available are very expensive or are only available under severely restrictive license agreements. Many of the available dyes have undesirable properties such as relatively high non-specific binding and a tendency to aggregate and are prohibitively expensive due in part to unoptimized synthetic methods and inadequate molecular design. The main focus of this work is to discover novel, long wavelength near-infrared dyes that are designed for use in biomedical in vivo imaging, high throughput screening and other applicable techniques such as immunofluorescence microscopy, fluorescence resonance energy transfer and fluorescence activated cell sorting and counting. Developments in imaging technologies have had a profound impact on clinical medicine including, ultrasound scanning, magnetic resonance imaging, x-ray computed tomography and nuclear tomography imaging. These systems are primarily used for displaying anatomical, physiological and metabolic parameters but they are increasingly being used in experimental animal systems for imaging at the cellular and molecular levels in vivo. These currently used imaging systems rely on physical parameters and properties to generate image contrast such as, sound impedance, electromagnetic wave impedance or nuclear alignments. In vivo fluorescence imaging offers more sensitive early stage detection of tumors that is very difficult to achieve with existing imaging techniques. Novel synthetic chemistry pathways will be developed that will allow gram-scale synthesis of the dyes in high purity and will result in products that will be more widely available to the research and scientific community.