Assessing the matrix effects on MALDI-MS in the positive and negative ion mode detection for protein-protected metal nanoclusters

Protein protected metal nanoclusters (NCs) represent a new class of highly photoluminescent nanomaterials that have wide applications. Suitable reaction conditions combining protein and metal precursors can produce a vast range of different NC sizes. The number of metal atoms per protein can be determined by mass spectrometry (MS). MS coupled with matrix-assisted laser desorption ionization (MALDI) presents a number of advantages such as detection with high sensitivity of nanoclusters with high molecular weights. Although many protein-protected metal nanoclusters have been characterized by MALDI-MS, a large dispersion in the number of metal atoms have been reported mainly due to sample preparation. In this work, we optimized the protocols for negative and positive ion detection mode as a general MALDI-MS sample preparation method for protein protected metal nanoclusters (bovine serum albumin and lysozyme and with gold and silver). Negative and positive ion mode detection was compared, showing that negative ion mode detection in MALDI-MS can also be used with acidic matrices. Obvious matrix effects on ion signals and peak positions by MALDI-MS was observed. The metal atom number of metal nanoclusters embedded in proteins is different depending on the MALDI matrix most probably due to fragmentation. The matrix effects give a warning for more serious consideration on MALDI-MS measurement and spectra analysis of nanoclusters.