Natural products are sources of inspiration and reservoir of high valuable molecules. Recently, analytical tools based on liquid chromatography coupled to tandem mass spectrometry to generate molecular network became widely employed for dereplication. This strategy greatly accelerates the identification of known and structural hypothesis of unknown. Despite the availability of different ionization sources, alternatives to classical electrospray ionization (ESI), such as atmospheric pressure chemical ionization (APCI) or photoionization (APPI), have been neglected. In particular, APPI has been described for its ionization efficiency on non-polar molecules bearing no acid or basic groups. For that reason, we investigated APPI potential to generate molecular network and compare it to ESI on several criteria that are generation of ion species, sensitivity and signal-to-noise ratio (SNR) for different extracts rich in highly conjugated natural products. We first optimized APPI experimental conditions on crude extract from a fungus, Penicillium sclerotiorum, producing polyketones belonging to the azaphilone family. Then we compared APPI and ESI on different fractions of the fungus and on two plant extracts, French Guyanese Swartzia panacoco (Aubl.) R.S. Cowan (arial parts) and Indian Cassia auriculata L. (leaves) containing phenolic compounds, such as flavonoids. While ESI generated more ion species and displayed a better sensitivity, APPI generated only protonated adduct and better SNR. Comparing ESI and APPI generated species on molecular network reveal that both strategies overlap for the majority of protonated ions.

天然产物是灵感的源泉和高价值分子的储存库。最近，基于液相色谱与串联质谱联用生成分子网络的分析工具被广泛用于去复制。该策略极大地加速了已知和未知结构假设的识别。尽管有不同的电离源，但经典电喷雾电离 (ESI) 的替代品，例如大气压化学电离 (APCI) 或光电离 (APPI)，却被忽视了。特别是，APPI 因其对不带酸或碱基团的非极性分子的电离效率而被描述。因此，我们研究了 APPI 生成分子网络的潜力，并在几个标准上将其与 ESI 进行比较，这些标准包括富含高度共轭天然产物的不同提取物的离子种类、灵敏度和信噪比 (SNR)。我们首先优化了真菌青霉菌粗提物的 APPI 实验条件，产生属于阿扎菲酮家族的聚酮。然后，我们比较了真菌不同部分和两种植物提取物的 APPI 和 ESI，即法国圭亚那Swartzia panacoco (Aubl.) RS Cowan（干部分）和印度决明(Cassia auriculata L.)（叶），其中含有酚类化合物（如类黄酮）。 ESI 产生更多离子种类并表现出更好的灵敏度，而 APPI 只产生质子化加合物和更好的 SNR。比较 ESI 和 APPI 在分子网络上生成的物种表明，这两种策略对于大多数质子化离子都是重叠的。