Vapour-Phase-Metalation Nanosurgery by ALD: A Tool for Single Molecular Replacement on Enterobactin for Drug Discovery and Nanomaterial Design

Abstract For the first time, the innovative vapour-phase metalation (VPM) process has been employed to functionalize soft materials such as Ferric Enterobactin (FeH x EB) and Enterobactin (H 6 EB) by linking ZnOH fragments, solely pulsing diethylzinc (DEZ). The samples were characterised through a suite of advanced techniques, including 1H and 13C 2D-HSQC nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, UV-Vis spectroscopy, and MALDI-TOF mass spectrometry (MS). Groundbreaking density functional theory calculations successfully correlated the IR and NMR data, shedding light on the profound influence of the ZnOH fragments on the architectures of FeH 3 EB and H 6 EB. Moreover, insightful molecular dynamics and molecular docking studies were conducted to explore the affinity energy between the ZnOH-modified and non-modified siderophore and the ferric protein enterobactin receptor (FepA). Spectroscopic analyses not only confirmed the successful Zn-modification of FeH 3 EB and H 6 EB but also underscored the potential of the VPM process for attaching metals to soft materials. The docking results revealed a compelling interaction between the ZnOH-modified siderophore and FepA, boasting an affinity equal to or even surpassing that of their unmodified counterparts. This work positions VPM as a cornerstone technology for atomic-level molecular engineering, with transformative implications across healthcare, materials science, and environmental sustainability.