TICT化合物分子内电荷转移平衡及在生物大分子体系中的平衡转化

Absorption of photons leads to the formation of excited state intramolecular charge transfer (ICT) in the molecules having both donor and acceptor moieties separated by a spacer triggers, whereas the emission takes place from the twisted ICT (TICT)state in a polar medium, caused by the electron donor twisting with respect to the rest of the molecule at an angle close to 90℃, exhibiting a highly Stokes-shifted and very weak fluorescence band. But the rotation of the molecule about this dihedral angle is also strongly affected by the micro-environment. The high sensitivity of TICT states and fluorescence properties towards the binding upon the macromolecules has been useful for biological probes. Some TICT compounds are therefore a promising candidate for investigating local protein or biomembrane conformational changes by reporting changes in microenvironmental polarity and solvation. The excited-state conversions from the LE state to the ICT state, and/or from the ICT to the TICT state, or the opposite conversions, is crucial in clarification of the recongnition mechanism for TICT probes. The estimation of thermodynamics of a possible ICT process on the basis of electrochemical and spectral data, in combination with DFT, TDDFT calculations, will gain some new insights into the conformational and photophysical behavior, correlation with the excited-state character in these D-A molecules. In this work, five kinds of D-A compounds with N-S conjugated system were synthesized for the study of ICT properties. The spectroscopy and electrochemical investigation combined with the theoretical calculation about structure and energy of ground and excited state of compounds of compounds will be performed. The thermodynamic evaluation of ICT ability for compounds and the equilibrium of in different media will be estabilished based on the measurement of various thermodynamic and kinetic constants, in order to answer the question regarding the specific factor that triggers the LE - TICT process. The effect of protein (serum albumin, or globulins), or liposomes/niosomes as two kinds of hosts on the LE or ICT (TICT) state of TICT compounds, as well as the thermodynamic equilibrium about charge transfer will be revealed in this project. It is a foundmental candidate for the mechanism of the recngnization of TICT compound to biomacramolecules.

具有扭转的分子内电荷转移激发态（TICT）的化合物凭借其特别的光学敏感性识别生物大分子，实质是化合物激发态分子内电荷转移途径的改变。对化合物在生物大分子中的激发态分子内电荷转移平衡和转化进行科学的热力学评价对揭示TICT化合物特异性识别的机制至关重要。本项目在设计合成具有丰富D-A结构的TICT化合物基础上，系统测定化合物的光谱、波谱、电化学性质，结合理论化学手段，研究化合物在不同环境中的分子内电荷转移过程，确定电荷转移过程参数，实现化合物电荷转移过程的热力学评价，建立与TICT相关的热力学平衡；以蛋白质（以血清蛋白、球蛋白）、脂质（不同极性的脂质体、囊泡）为代表，评价化合物在生物大分子中的分子内电荷转移能力和途径，关注平衡转化方向和程度，结合TICT化合物与生物大分子的相互作用模型、驱动力和热力学参数等，揭示生物大分子体系对化合物分子内电荷转移平衡的调控机制。

按照项目研究计划，实际设计合成芳香杂环类化合物150多个，通过对化合物的光化学，光物理及电化学性质的系统测试，结合理论计算化学手段，筛选出30多个具有TICT性质的结构。研究这些化合物在在不同结构蛋白质，脂质体等生物大分子体系中与ICT、TICT性质有关的构效关系，以系统实验结合理论模拟的方式，揭示化合物对生物大分子进行特异性识别，产生光开关信号的分子机制，发现TICT的平衡与转化在分子识别中发挥重要作用。得到了一系列发光波长长（> 600 nm），灵敏、具有特异性响应的生物分子探针结构。研究证实，这些探针化合物在生物大分子体系中，均可实现“OFF-ON”或者“OFF-ON-OFF”光信号转换，其机理均与TICTICT平衡转化有关。针对光活性化合物（光化学探针）在不同结构蛋白质、核酸及其剪切酶、不同结构组装的脂质体中的光信息变化，定性定量研究作用机制、作用力，从化合物在光化学识别过程中涉及的TICTICT平衡及转化路线阐明在特殊结构大分子的鉴别化识别中的机制和应用。