VIBRATIONAL OPTICAL ACTIVITY IN BIOMOLECULES

振动光学活性(VOA)，一种分子间的微分相互作用 具有左右圆偏振辐射的手性分子 振动激励，测量吸收(振动圆环 二向色性，VCD)和拉曼散射(拉曼光学活性，ROA)， 将作为一种生物光谱技术进一步开发和应用。 VCD和ROA仪器的升级将允许测量 美国之音在更大的频率范围和较低的样本浓度下， 和从头算分子轨道形式的实现 VCD和ROA强度的计算将增强和细化 对美国之音频谱的解释，目标是将美国之音确立为 生物分子光谱学中可以补充的主要技术 电子CD、核磁共振、傅里叶变换红外光谱和X射线结晶学研究。应用 从VOA到中小型原生生物分子和模型生物分子将提供 有关活性溶液构象的唯一信息。具体来说，我们 提出了以下建议：(1)氢气中VCD光谱的测量 将改进拉伸区域和VCD光谱的获取 将扩展到近红外区的泛音和组合 通过升级我们的色散式VCD光谱仪以包括步进扫描 FT-IR技术。我们将继续强调氢气的测量 拉伸模式因其简单的局域化性质而被用作 局域构象、分子内缔合和氢键的探针 凝聚力。(2)我们的ROA仪器将进行升级和优化，以 安装背面变薄的CCD阵列探测器在生物应用中的应用 并用基于全息色散的光谱仪取代光谱仪 和成像技术。这些改进将允许探索 共振ROA和表面增强ROA，扩展ROA测量 更稀释的解决方案。(3)VCD和ROA光谱的解释将 既强调经验关联又强调从头算分子轨道 频率、优化几何形状和VOA强度的计算， 它将通过核速度的实施而增强 摄动速度规VCD的先验形式，局部化 VCD的起源规范从头算模型和新的态和从头算 居留权的形式主义。显示振动产生的电流的地图 (对于VCD)和感应电流(对于ROA)将被开发以获得洞察力 关于美国之音强度大的机制。(4)的具体应用 美国之音提供生物分子溶液构象的信息， 其中包括世界范围内的样品合成合作和 补充测量，将包括ROA和VCD调查 形成β-转角的小的生物活性和模型肽，VCD 免疫抑制环肽环孢素与多种溶剂的作用 并添加阳离子，形成3(10)螺旋和β-螺旋的多肽的ROA。 手性药物小分子的带状螺旋和VOA研究 如AZT和感觉分子如阿斯巴甜。关于《红楼梦》VCD的研究 与血红素蛋白结合的各种配体将继续 表征手性亚铁血红素结合部位。将开发共振ROA 通过将胆红素与奎宁和阿司匹林等手性试剂络合 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.