Structural characterization of new defective molecules in poly(amidoamide) dendrimers by combining mass spectrometry and nuclear magnetic resonance

• ESI-MS/MS and NMR were combined to elucidate a new side-reaction during divergent synthesis of PAMAM dendrimers.
• These new impurities exhibit a net gain of a single carbon atom as compared to expected molecules.
• The side-reaction is due to formaldehyde, contained as trace level impurity in methanol used as the synthesis medium.

A new side-reaction occurring during divergent synthesis of PAMAM dendrimers (generations G0–G2) was revealed by mass spectrometric detection of defective molecules with a net gain of a single carbon atom as compared to expected compounds. Combining MS/MS experiments performed on different electrosprayed precursor ions (protonated molecules and lithiated adducts) with NMR analyses allowed the origin of these by-products to be elucidated. Modification of one ethylenediamine end-group of perfect dendrimers into a cyclic imidazolidine moiety was induced by formaldehyde present at trace level in the methanol solvent used as the synthesis medium. Dendrimers studied here were purposely constructed from a triethanolamine core to make them more flexible, as compared to NH3- or ethylenediamine-core PAMAM, and hence improve their interaction with DNA. Occurrence of this side-reaction would be favored by the particular flexibility of the dendrimer branches.

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