Probing changes of noncovalent interactions is crucial to study the binding efficiencies and strengths of (bio)molecular complexes. While surface-enhanced Raman scattering (SERS) offers unique molecular fingerprints to examine such interactions in situ, current platforms are only able to recognize hydrogen bonds because of their reliance on manual spectral identification. Here, we differentiate multiple intermolecular interactions between two interacting species by synergizing plasmonic liquid marble-based SERS platforms, chemometrics, and density functional theory. We demonstrate that characteristic 3-mercaptobenzoic acid (probe) Raman signals have distinct peak shifts upon hydrogen bonding and ionic interactions with tert-butylamine, a model interacting species. Notably, we further quantify the contributions from each noncovalent interaction coexisting in different proportions. As a proof-of-concept, we detect and categorize biologically important nucleotide bases based on molecule-specific interactions. This will potentially be useful to study how subtle changes in biomolecular interactions affect their structural and binding properties.

中文翻译：

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使用SERS和化学计量学原位区分多重非共价相互作用。

探测非共价相互作用的变化对于研究（生物）分子复合物的结合效率和强度至关重要。尽管表面增强拉曼散射（SERS）提供了独特的分子指纹来原位检查这种相互作用，但是当前的平台由于依赖于手动光谱识别而只能识别氢键。在这里，我们通过协同基于等离子液体大理石的SERS平台，化学计量学和密度泛函理论来区分两个相互作用物种之间的多个分子间相互作用。我们证明特征性的3-巯基苯甲酸（探针）拉曼信号在氢键和与叔离子的离子相互作用上具有明显的峰移-丁胺，一种相互作用的模型。值得注意的是，我们进一步量化了每种非共价相互作用以不同比例共存的贡献。作为概念验证，我们根据分子特异性相互作用对生物学上重要的核苷酸碱基进行检测和分类。这对于研究生物分子相互作用中的细微变化如何影响其结构和结合特性可能很有用。