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.
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