College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 145040, China.
State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
Anal Chem. 2024 Jun 25;96(25):10365-10372. doi: 10.1021/acs.analchem.4c01437. Epub 2024 Jun 13.
Biomimetic cytochrome P450 for chemical activation of environmental carcinogens is an efficient model for evaluating their mutagenicity and ultimately acquiring the metabolites that cannot be easily accessed by conventional routes of organic synthesis. Different kinds of mutagen derived from polyaromatic hydrocarbons (PAHs) by metalloporphyrin/oxidant model systems have been reported, but the underlying molecular mechanisms are poorly understood. Herein, we have for the first time demonstrated an effective surface-enhanced Raman scattering (SERS) protocol to study the dynamics and biomimetic metabolic behaviors of pyrene (Pyr) in the presence of various oxygen donors. Quantitative information on the relative concentration of Pyr and its metabolites in the biomimetic system can be extracted from the SERS spectra. On the basis of our results, we conclude that the oxidative metabolism of Pyr is highly influenced by the types and concentrations of oxygen donors, leading to the formation of 1-hydroxypyrene and dioxygenated products. Besides, the addition of an appropriate amount of an organic solvent can promote the formation of secondary oxidation products. These results offer valuable insights into the dynamics of PAHs metabolism and the regulation of their metabolic pathways in biomimetic activation. In comparison to traditional liquid chromatography-mass spectrometry, the present SERS approach is more suitable for high-throughput evaluation of the metabolic process and kinetics of PAHs. We anticipate that this approach will enable a more general and comprehensive tracking of metabolic dynamics and molecular mechanisms involved in the biomimetic activation of other xenobiotics, such as procarcinogens, promutagens, and drugs.
仿生细胞色素 P450 可用于化学激活环境致癌物，是评估其致突变性的有效模型，最终可获得通过传统有机合成方法难以获得的代谢物。已有文献报道了多种多环芳烃（PAHs）通过金属卟啉/氧化剂模型系统衍生的诱变剂，但对其潜在的分子机制了解甚少。本文首次提出了一种有效的表面增强拉曼散射（SERS）方案，用于研究在不同氧供体存在下苝（Pyr）的动力学和仿生代谢行为。通过 SERS 光谱可提取仿生体系中 Pyr 及其代谢物的相对浓度的定量信息。基于我们的结果，我们得出结论，Pyr 的氧化代谢受氧供体的类型和浓度的强烈影响，导致 1-羟基苝和双加氧产物的形成。此外，添加适量的有机溶剂可以促进二次氧化产物的形成。这些结果为 PAHs 代谢动力学和仿生激活中代谢途径的调控提供了有价值的见解。与传统的液相色谱-质谱法相比，本 SERS 方法更适合于高通量评估 PAHs 代谢过程和动力学。我们预计，这种方法将能够更普遍和全面地跟踪其他外源性化合物（如前致癌物、促突变剂和药物）仿生激活中涉及的代谢动力学和分子机制。
