Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) is applied for the investigation of C2-ceramide complexes with transition metal ions. Ceramide plays an important role in the regulation of various signaling pathways leading to proliferation, differentiation or apoptotic cell death. The formation and fragmentation of doubly charged cluster ions as well as singly charged cluster ions of C2-ceramide with transition metal ions (Mn2+, Fe2+, Co2+ and Ni2+) are studied by ESI-MS/MS in the positive mode. Tube lens offset voltage and concentrations of C2-ceramide and transition metals are optimized to determine the best conditions for generating doubly charged cluster ions. The fragmentation pathways of metal ion complexes with C2-ceramide and the compositions of these complexes are determined by collision induced dissociation (CID). All transition metal ions (Mn2+, Fe2+, Co2+ and Ni2+ except Cu2+) shows similar complexation with C2 ceramide. The unique complexation behavior of copper(II) is responsible for the different geometry of the complexes and relatively lower affinity of ceramide to copper(II) than those to other transition metals.
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