Mass spectrometry based fragmentation patterns of nitrosamine compounds.

RATIONALE: Nitrosamines are a class of mutagenic substances that can display high carcinogenic potential. New chemical entities may have the potential to form unique nitrosamines specific to the drug substance. It is therefore essential to understand the gas-phase fragmentation behavior of nitrosamine compounds to enable the development of analytical methods to characterize novel nitrosamine compounds. METHODS: The gas-phase fragmentation behavior of eight model nitrosamine compounds representing the common substructures seen in many small molecule pharmaceutical compounds was studied with positive electrospray ionization tandem mass spectrometry (ESI-MS/MS). The fragmentation patterns of these compounds under various collision parameters available in commercially available mass spectrometers were studied. RESULTS: Protonated nitrosamine compounds produced diagnostic fragment ions upon MS/MS. Three primary structure-dependent fragmentation pathways were observed. The first pathway involves the loss of 30 Da which corresponds to the loss of the NO radical from the protonated nitrosamine compound (Group 1). The second and third fragmentation pathways, which have not been reported for nitrosamine compounds, proceed via the loss of H2 O from the protonated nitrosamine compound (Group 2), and elimination and a loss of 46 Da (loss of NH2 NO) from the nitrosamine compound (Group 3). CONCLUSIONS: Results presented in this work provide an overview of the gas-phase fragmentation patterns of nitrosamine compounds and may be useful in identifying novel nitrosamine compounds in complex matrices.

Exploring the Effect of Amphiphilic Polymer Architecture: Synthesis, Characterization, and Self-Assembly of Both Cyclic and Linear Poly(ethylene gylcol)-b-polycaprolactone.

While amphiphilic block copolymers have demonstrated their utility for a range of practical applications, the behavior of cyclic block copolymers remains largely unexplored due to limited synthetic access. To investigate their micelle formation, biocompatible cyclic amphiphilic poly(ethylene glycol)-polycaprolactone, c-(PEG-PCL), was synthesized by a combination of ring-opening polymerization (ROP) and click chemistry. In addition, exactly analogous linear block copolymers have been prepared as a control sample to elucidate the role of polymer architecture in their self-assembly and acid-catalyzed degradation.

A versatile and modular approach to functionalisation of deep-cavity cavitands via"click" chemistry.

The surface modification of deep-cavity cavitands has been demonstrated by using the azide-alkyne "click" coupling to attach dendritic macromolecules or linear polymers onto their periphery. The resulting set of macromolecular cavitands exhibited tuneable solubility yet retained the ability to encapsulate guest molecules.

The identification of synthetic homopolymer end groups and verification of their transformations using MALDI-TOF mass spectrometry.

Recent advances in the resolving power of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) enable the detailed characterization of linear homopolymers, and in particular provide invaluable data for the determination of their end-group functionalities. With the growing importance of macromolecular coupling reactions in building complex polymer architectures, the ability to accurately monitor end-group transformations is becoming increasingly important for synthetic polymer chemists. This tutorial demonstrates the application of MALDI-TOF MS in determining both end-group functionalities and their transformations for linear homopolymers. Examples of both polycaprolactone and polystyrene are examined, and the strengths and weaknesses of various approaches to data analysis are given.