Plier Ligands for Trapping Neurotransmitters into Complexes for Sensitive Analysis by SERS Spectroscopy

Abstract

Catecholamines–dopamine, noradrenaline and adrenaline are important biomarkers of neurotransmitter metabolism, indicating neuroendocrine tumors and neurodegenerative diseases. Surface-enhanced Raman spectroscopy (SERS) is a promising analytical technique with unprecedented multiplexing capabilities. However, not all important analytes exhibit strong SERS signals on stable and robust nanostructured substrates. In this work, we propose a novel indicator system based on the formation of mixed ligand complexes with bispidine-based bis-azole ligands which can serve as pliers to trap Cu(II) ions and stabilize its complexes with catecholamines. Four synthesized ligands with different functional groups: carboxyl, amino, benzyl, and methoxybenzyl, were applied for forming stable complexes to shift maximum absorbance of catecholamines from the ultraviolet region to 570–600 nm. A new absorbance band in the visible range resonates with the local surface plasmon resonance (LSPR) band of metal nanoparticles and most used laser wavelengths. This match allowed use of Molecular Immobilization and Resonant Raman Amplification by Complex-Loaded Enhancers (MIRRACLE) methodology to measure intense Raman signals on a nanostructured silver-based SERS-active substrate. The synthesized plier-like ligands fixed and stabilized catecholamine complexes with Cu(II) on the SERS sensor surface, which facilitated the determination of dopamine in a 3.2 × 10−12–1 × 10−8 M concentration range.