VIBRATIONAL OPTICAL ACTIVITY IN BIOMOLECULES

振动旋光性（VOA），一种 具有左右圆偏振辐射的手性分子 振动激发，测量吸收（振动圆 二向色性，VCD）和拉曼散射（拉曼光学活性，罗阿）， 将作为生物光谱技术进一步发展和应用。 VCD和罗阿仪器升级后， VOA在更宽的频率范围和更低的样品浓度下， 的从头算分子轨道形式和实现 VCD和罗阿强度的计算将增强和细化 解释VOA光谱，目的是建立VOA作为一个 生物分子光谱学的主要技术， 电子CD、NMR、FTIR和X射线晶体学研究。应用 VOA的小到中等大小的天然和模型生物分子将提供 关于活性溶液构象的唯一信息。我们特别 提出了以下几点建议：（1）氢气中VCD谱的测量 拉伸区域将得到改善，VCD光谱的获取 将扩展到近红外波段的泛音和组合 波段通过升级我们的色散VCD光谱仪，包括步进扫描 FT-IR技术。我们将继续强调氢的测量 由于它们简单的局部化性质和它们作为 探针的局部构象和分子内协会和氢- 前将芯片(2)我们的罗阿仪器将进行升级和优化， 通过安装背衬变薄CCD阵列探测器的生物应用 用基于全息色散的摄谱仪代替摄谱仪 和成像技术。这些改进将允许探索 共振罗阿和表面增强罗阿，并扩展了罗阿的测量 更稀的溶液(3)VCD和罗阿光谱的解释将 强调经验关联和从头算分子轨道 计算频率，优化几何形状和VOA强度， 这将通过实施核速度来加强 VCD的扰动速度规范先验形式，局部化的 VCD的原点规范从头算模型和新的满态求和从头算 罗阿的形式主义。振动产生的电流图的显示 (for VCD）和感应电流（用于罗阿），以了解 大VOA强度的机制。(4)的具体应用 美国之音提供关于生物分子的溶液构象的信息， 这涉及到全球范围内的样品合成合作， 补充测量，将包括罗阿和VCD调查， 形成β-转角的小生物活性和模型肽， 具有多种溶剂的免疫抑制性环肽环孢菌素 和添加的阳离子，形成3（10）-螺旋和β- 带状螺旋和VOA研究小手性药物分子 比如AZT和感觉分子比如阿糖胞苷中国的VCD研究 将继续研究与血红素蛋白结合的各种配体， 表征手性血红素结合位点。将开发共振罗阿 通过使用胆红素与手性试剂如奎宁络合， 白蛋白。

Vibrational optical activity (VOA), the differential interaction of a chiral molecule with left and right circularly polarized radiation during vibrational excitation, measured for absorption (vibrational circular dichroism, VCD) and for Raman scattering (Raman optical activity, ROA), will be further developed and applied as a biospectroscopic technique. Upgrades in both VCD and ROA instrumentation will permit measurement of VOA over a wider range of frequencies and at lower sample concentrations, and implementation of ab initio molecular orbital formalisms for calculation of VCD and ROA intensities will enhance and refine the interpretation of VOA spectra, with a goal of establishing VOA as a principal technique in biomolecular spectroscopy that can complement electronic CD, NMR, FTIR and x-ray crystallography studies. Applications of VOA to small to medium sized native and model biomolecules will provide unique information on active solution conformations. Specifically, we propose the following: (1) Measurement of VCD spectra in the hydrogen stretching regions will be improved and the acquisition of VCD spectra will be extended into the near-infrared region of overtone and combination bands by upgrade of our dispersive VCD spectrometer to include step-scan FT-IR technology. We will continue to emphasize measurement of hydrogen stretching modes due to their simple localized nature and their use as probes of local conformation and intramolecular associations and hydrogen- bonding. (2) Our ROA instrument will be upgraded and optimized for biological applications by installing a back-thinned CCD array detector and replacing the spectrograph with one based on holographic dispersion and imaging technology. These improvements will permit the exploration of resonance ROA and surface-enhanced ROA, and extend the measurement of ROA to more dilute solutions. (3) Interpretation of VCD and ROA spectra will emphasize both empirical correlation and ab initio molecular orbital calculation of frequencies, optimized geometries and VOA intensities, which will be enhanced by implementation of the nuclear-velocity perturbation velocity-gauge a priori formalism for VCD, the localized origin gauge ab initio model for VCD and new sum-over-states ab initio formalism for ROA. The display of maps of vibrationally generated current (for VCD) and induced current (for ROA) will be developed to gain insight into the mechanisms for large VOA intensity. (4) Specific applications of VOA to provide information on solution conformations of biomolecules, which involve collaborations world-wide for sample synthesis and complementary measurements, will include ROA and VCD investigations of small bioactive and model peptides that form beta-turns, VCD of the immunosuppressive cyclic peptide cyclosporin with a variety of solvents and added cations, the ROA of peptides that form 3(10)-helices and beta- ribbon spirals, and VOA studies on small chiral pharmaceutical molecules such as AZT and sensory molecules such as aspartame. Studies of the VCD of a variety of ligands bound to heme proteins will be continued to characterize the chiral heme binding site. Resonance ROA will be developed by using bilirubin complexed with chiral agents such as quinine and albumin.