Initiation of radical polymerization by peroxyacetates: Polymer end-group analysis by electrospray ionization mass spectrometry

End-groups of poly(methyl methacrylate) from radical solution polymerization of MMA using tert-butyl peroxyacetate (TBPA), tert-amyl peroxyacetate (TAPA), 1,1,2,2- tetramethylpropyl peroxyacetate (TMPPA), and 1,1,3,3-tetramethylbutyl peroxyacetate (TMBPA) as the initiators were analyzed via electrospray ionization mass spectrometry (ESI-MS). The type and the relative concentration of the radical species, which actually initiate macromolecular growth, are determined. In the majority of cases, these species differ from the primary radicals from thermal decomposition of the peroxyacetates. Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was applied for unambiguous peak assignment. The methylcarbonyloxyl radical, which is formed by the decomposition of all peroxyacetates, was found to undergo decarboxylation yielding an initiating methyl radical. TAPA- and TMPPA-derived alkoxyl radicals mainly show β-scission, TMBPA-derived alkoxyl radicals additionally undergo a 1,5-hydrogen-shift reaction. The tert-butoxyl radicals produced from TBPA undergo pronounced chain-transfer reaction prior to their decomposition into methyl radicals and acetone. In the case of using benzene as a relatively inert solvent, the tert-butoxyl radicals exhibit transfer to monomer yielding polymer molecules, which do not carry any initiator-derived end-groups. By using mesitylene as a cosolvent, small amounts of star polymer were generated via multiple hydrogen abstraction by tert-butoxyl radicals from the three individual methyl groups of mesitylene. This uncomplicated procedure of modification of end-group and polymer topology may be attractive for facile adjustment of polymer viscosity in technical processes. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2453–2467, 2007     

Investigation of the transformations of a novel anti-cancer agent combining HPLC, HPLC–MS and direct ESI–HRMS analyses

One of the main problems of anti-cancer therapy is an insufficient differentiation between normal and malignant cells by the known anti-proliferant agents. The antibody-directed enzyme prodrug therapy is a promising approach for a selective treatment of cancer, in which a non-toxic prodrug is enzymatically converted into a highly cytotoxic drug at the surface of malignant cells by a targeted antibody–enzyme conjugate. The transformations and the stability of a very promising novel prodrug and its corresponding cytotoxic derivative were now investigated in detail by high-performance liquid chromatography (HPLC)–mass spectrometry (MS). In order to determine the time-dependent DNA alkylation efficiency and the sequence selectivity of the novel compounds, DNA binding studies using direct electrospray–Fourier transform ion cyclotron resonance–MS (ESI–FTICR–MS) have been performed. These measurements were accompanied by HPLC analyses followed by MS of the separated species to confirm the results of the direct ESI–FTICR–MS measurements. The sites of DNA alkylation could be identified unambiguously by the mass spectrometric fragmentation pattern of the alkylated oligodeoxynucleotides as well as by the results of HPLC followed by MS. A combination of all techniques applied led to a better understanding of the mode of action of the new therapeutics and might be used for an estimation of the cytotoxicity of different prodrugs and drugs since the alkylation efficiency correlates with the bioactivity of the compounds in cell culture investigations. After enzymatic cleavage of the sugar moiety, the untoxic prodrug is converted rapidly into the corresponding highly cytotoxic drug that alkylates DNA with high efficiency Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.