Characterization of Soluble Polymer Supported Organic Molecules by Mass Spectrometry

摘要

Syntheses carried out on soluble polymers, such as polyethylene glycol (PEG), benefit the advantages of both solution-phase and solid-phase syntheses. The choice of the reaction solvent governs the polymer solubility. Synthetic steps are conducted under homogeneous conditions whereas purifications are performed by filtration after polymer precipitation. This alternative strategy, known as liquid-phase chemistry, has been investigated to prepare combinatorial libraries. The fact that soluble polymer supported molecules are directly amenable to standard spectroscopic methods, including NMR (~1H, ~(13)C) and ESI or MALDI mass spectrometry (ElectroSpray and Matrix Assisted Laser Desorption Ionization) allows to perform to in situ reaction monitoring without the need to release the compound from the polymeric support. We report a general methodology to characterize step by step soluble polymer supported organic molecules by MALDI and ESI mass spectrometry. High throughput analyses were targeted to fullfil combinatorial chemistry requirements. Data acquisition and interpretation were automated through the design of specific experimental protocols and a data managment software. MALDI mass spectrometry was appropriate to analyze pure supported molecules whereas ESI mass spectrometry coupled to liquid chromatography was required to unravel PEG mixtures.