Distinguishing positional isomers, such as compounds having different substitution patterns on an aromatic ring, presents a significant challenge for mass spectrometric analyses and is a frequently encountered difficulty in, for example, drug metabolism research. In contrast to mass spectrometry, IR spectroscopy is a well-known and powerful tool in the distinction of ortho-, meta- and para-isomers, but is not applicable to low-abundance compounds in complex mixtures such as often targeted in bioanalytical studies. Here, we demonstrate the use of infrared ion spectroscopy (IRIS) as a novel method that facilitates the differentiation between positional isomers of disubstituted phenyl-containing compounds and that can be applied in mass spectrometry-based complex mixture analysis. By analyzing different substitution patterns over several sets of isomeric compounds, we show that IRIS is able to consistently probe the diagnostic CH out-of-plane vibrations that are sensitive to positional isomerism. We show that these modes are largely independent of the chemical functionality contained in the ring substituents and of the type of ionization. We also show that IRIS spectra often identify the positional isomer directly, even in the absence of reference spectra obtained from physical standards or from computational prediction. We foresee that this method will be generally applicable to the identification of disubstituted phenyl-containing compounds.

中文翻译：

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基于质谱的红外离子光谱法鉴定邻，间和对位异构体。

区分位置异构体，例如在芳香环上具有不同取代模式的化合物，对质谱分析提出了重大挑战，并且在例如药物代谢研究中经常遇到困难。与质谱相比，IR光谱是区分邻位，间位和对位的众所周知的强大工具-异构体，但不适用于复杂混合物中的低丰度化合物，例如通常在生物分析研究中所针对的化合物。在这里，我们演示了红外离子光谱（IRIS）作为一种新方法的使用，该方法有助于区分含双取代苯基的化合物的位置异构体，并且可以应用于基于质谱的复杂混合物分析中。通过分析几套异构化合物上的不同取代模式，我们表明IRIS能够始终如一地探测对位置异构现象敏感的诊断CH面外振动。我们表明，这些模式很大程度上与环取代基中所含的化学官能度和电离类型无关。我们还表明，IRIS光谱通常可以直接识别位置异构体，即使没有从物理标准或计算预测获得的参考光谱。我们预见到，该方法通常可用于鉴定双取代的含苯基化合物。