DENDRITIC O2 SENSOR WITH TWO-PHOTON ABSORBING ANTENNA

描述(申请人提供)：我们建议构建一种纳米级的氧气分子传感器，它将利用双光子(2P)吸收现象，允许使用双光子激光扫描显微镜(2P LSM)对各种生物对象进行高分辨率的氧气测量，包括体内脑神经元的氧气成像。纳米传感器的设计将结合目前在纳米科学和纳米技术应用中受到仔细审查的几个原则和元素。这些将包括：双光子吸收(2PA)；由耦合到同一功能核心的多个发色体组成的天线阵列；从天线到核心的定向分子内能量转移(ET)；核心功能的树枝状封装，以提供其对其局部环境的保护和控制。简而言之，1)该装置的中心部件作为激发能量的末端接受者，将是一个多功能的铂或钯卟啉，它的三重态发射很强，发生在近红外，对O2敏感：2)由于金属卟啉的2PA截面很小，几个强的2P吸收体将直接或连接到连接在卟啉上的树枝状臂的末端，提供一个有效的2P天线；3)2P发色团的选择将使其2P吸收带位于组织的近红外窗口(例如700-900 nm)，而其发射将最大限度地与核心金属卟啉的吸收带(S)重叠，以确保有效的天线-GT；能量转移(ET)；4)核心金属卟啉上未用于耦合天线的官能团将被用于连接保护树突；这些将形成包覆层，隔离核心与生物成分的相互作用，控制氧的扩散，使整个传感器水溶性。除了是2P活体氧成像的关键外，该结构还将是在单分子水平上研究三重态发射和氧猝灭的优秀模型化合物。如果成功，这些实验将为新的研究开辟道路，从小分子扩散的蛋白质构象研究到单分子氧传感器的构建。

DESCRIPTION (provided by applicant): We propose to construct a nano-scale molecular sensor for oxygen, which will take advantage of the two-photon (2P) absorption phenomenon, permitting high-resolution O2 measurements in a variety of biological objects, including oxygen imaging in brain neurons in vivo, using two photon laser scanning microscopy (2P LSM). The design of the nano-sensor will combine several principles and elements, currently under scrutiny in nano-science and nano-technology applications. These will include: two-photon absorption (2PA); an antenna-array, consisting of multiple chromophors coupled to the same functional core; directional intramolecular energy transfer (ET) from the antenna to the core; dendritic encapsulation of the core function to provide its protection and control of its local environment. In brief, 1) the central component of the device, serving as the terminal acceptor of the excitation energy, will be a polyfunctionalized Pt or Pd porphyrin, whose triplet state emission is strong, occurs in the near infra-red and is sensitive to O2; 2) because 2PA cross sections of metalloporphyrins are small, several strong 2P absorbers will be linked to the core, either directly or to the termini of dendritic arms attached to the porphyrin, providing an efficient 2P antenna; 3) the 2P chromophors will be chosen in such a way that their 2P absorption bands will be in the near infra-red window of tissue (e.g. 700-900 nm), while their emission will be maximally overlapped with the absorption band(s) of the core metalloporphyrin, assuring efficient antenna ->remitter energy transfer (ET); 4) the functional groups on the core metalloporphyrin unused in the coupling of the antenna will be used for attaching the protecting dendrons; these will form an encapsulating jacket, isolating the core from interactions with biological components, controlling diffusion of oxygen and making the entire sensor water-soluble. In addition to being the key to 2P in vivo oxygen imaging, the proposed construct will be an excellent model compound to study triplet state emission and oxygen quenching at the single molecule level. If successful, these experiments will open avenues for novel research, which will span from the studies of protein conformations by small molecule diffusion to the construction of a single-molecule oxygen sensor.