CE-ESI-MS for the investigation of antitumor agents

For the specific design of new metal complexes with antitumor activity it is important to know as much as possible about their mode of action, their behaviour under physiological conditions (hydrolysis), plasma bindings, transport mechanisms and so on. A very usefull tool to obtain structural information can be NMR spectroscopy. However it is useless for Ru (III) complexes due to its paramagnetism. Other useffill techniques are mass spectrometry (MS) and x-ray structure analysis. To get more detailed information about metabolism and hydrolysis capillary electrophoresis (CE) is very helpfull as it enables the operation under pure aqueous conditions. We intend to investigate the mode of action and the behaviour under physiological conditions of tumor-inhibiting metal complexes at the molecular level by means of CE and CE-ESI-MS. We would focus on platinum and ruthenium compounds and their interaction with nucleotides. For the Ru (III) complexes we would also focus on the hydrolysis of the original complexes under physiological conditions. The obtained results should lead to a better knowledge of the mode of action of the tumor-inhibiting metal complexes and moreover to an improved design of new metal-based antitumor drugs. The feedback obtained from these analytical investigations about the behaviour of newly synthesized compounds can directly be used for new preparation strategies. For this project CE-ESI-MS is best suited because it gives the possibility of working under aqueous conditions and MS is still the most selective detection method, because of its possibility to focus on single mass tracks. The huge selectivity of MS can be very important when working with biological samples and complex matrices. It is a very sensitive method for ionic analytes and enables unambiguous determination of the molecular mass of the separated analytes and gives further information about the structure of the compounds by using MS/MS. Electrospray ionization (ESI) interfacing is currently the method of choice to combine capillary separation techniques with MS and is best suited for the project purposes.