van Outersterp Rianne E, Martens Jonathan, Berden Giel, Koppen Valerie, Cuyckens Filip, Oomens Jos
Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7, 6525ED Nijmegen, The Netherlands.
Analyst. 2020 Sep 14;145(18):6162-6170. doi: 10.1039/d0an01119c.
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.
区分位置异构体，例如在芳环上具有不同取代模式的化合物，对质谱分析来说是一项重大挑战，并且是例如药物代谢研究中经常遇到的难题。与质谱法不同，红外光谱法是区分邻位、间位和对位异构体的一种众所周知且强大的工具，但不适用于生物分析研究中经常针对的复杂混合物中的低丰度化合物。在此，我们展示了红外离子光谱法（IRIS）作为一种新方法的应用，该方法有助于区分含二取代苯基化合物的位置异构体，并且可应用于基于质谱的复杂混合物分析。通过分析几组异构体化合物的不同取代模式，我们表明IRIS能够一致地探测对位置异构敏感的诊断性CH面外振动。我们表明，这些模式在很大程度上与环取代基中所含的化学官能团以及电离类型无关。我们还表明，即使在没有从物理标准品或计算预测获得的参考光谱的情况下，IRIS光谱通常也能直接识别位置异构体。我们预计该方法将普遍适用于含二取代苯基化合物的鉴定。
