Cross-reactivities in conjugation reactions involving iron oxide nanoparticles

We use 3,4-dihydroxybenzoic acid-functionalized IONPs (IONP-3,4-DHBA) as a platform upon which carbodiimide coupling can be used to conjugate clickable small molecules for further functionalization using two common click reactions: the copper catalyzed azide-alkyne cycloaddition (CuAAC), and the thiol-maleimide Michael addition reactions. Through the judicious use of controls, we demonstrate significant cross-reactivities of amines, thiols, maleimides, and common disulfide reducing agents with surface Fe of IONPs and show how these unwanted interactions can produce false positive results. Without proper controls, these can lead to erroneous conclusions about the efficacy of conjugation reactions, which can have detrimental impacts on the functionality and safety of IONPs in biomedical applications. Herein, we include the spectrum files for all UV-vis, FTIR and XPS results.

本研究采用3,4-二羟基苯甲酸功能化氧化铁纳米颗粒（IONP-3,4-DHBA，Iron Oxide Nanoparticles，简称IONPs）作为载体平台，通过碳二亚胺偶联反应将可点击小分子偶联至该载体表面，后续可通过两种经典点击反应实现进一步功能化：铜催化叠氮-炔环加成（CuAAC）以及巯基-马来酰亚胺迈克尔加成反应。通过合理设置对照组，我们证实胺类、巯基类、马来酰亚胺类化合物及常见二硫键还原剂可与氧化铁纳米颗粒表面的铁元素发生显著交叉反应，并阐明此类非特异性相互作用如何引发假阳性结果。若未采用恰当的对照组，上述问题可能会导致偶联反应有效性的结论出现错误，进而对氧化铁纳米颗粒在生物医学应用中的功能与安全性造成不利影响。本数据集包含所有紫外-可见光谱（Ultraviolet-Visible Spectroscopy, UV-vis）、傅里叶变换红外光谱（Fourier Transform Infrared Spectroscopy, FTIR）以及X射线光电子能谱（X-ray Photoelectron Spectroscopy, XPS）的原始谱图文件。