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Final Activity Report Summary - PHANTAGEN (Photoactivatable platinum(IV)-diazide complexes: a new generation of platinum-based anticancer agents)

We managed to understand the solution properties and possible photoactivation pathways of some photoactivatable Pt(IV)-diazido derivatives, thus providing us with new insights into their mechanism of action as potential anticancer agents.

These studies were carried out by means of several spectroscopic techniques including 14N/15N Nuclear magnetic resonance (NMR), [1H,15N] Heteronuclear single quantum correlation or Heteronuclear multiple-bond correlation (HSQC/HMBC) NMR and Electrospray ionisation mass spectrometry (ESI-MS). They proved to be highly challenging, as the peculiarity of the investigated systems presented some obstacles regarding both mapping out the photoreduction pathways and finding the optimal experimental conditions. In particular, 15N NMR methods did not turn out to be as hoped.

In order to overcome these problems, we came up with the development and optimisation of different and more suitable analytical techniques to investigate reaction intermediates, major photoproducts and side-products. The optimal experimental conditions, e.g. concentration, temperature, pH, irradiation wavelength and power etc., were investigated in detail. In particular, the use of 14N NMR spectroscopy was shown to be a reliable method to follow the evolution of the investigated compounds upon irradiation, allowing for the identification of both the major photoproducts and the possible photoreduction mechanisms, leading to unexpected and unprecedented results.

In addition, the ability of these Pt(IV)-diazido complexes to bind Deoxyribonucleic acid (DNA) under irradiation with both visible and Ultraviolet (UV) light, the binding extent and the identification of the binding sites on nucleobases were successfully investigated, as well as the complexes' binding properties to other biologically-relevant biomolecules.

According to our results, two different mechanisms were identified and examined in detail, leading to the conclusion that the photoreaction pathways appeared to be highly dependent on the solution conditions, such as solvent, pH and concentration, and the presence of biomolecules.

This study also led to exciting advantages, found in parallel to the main investigation. In fact, this photoactivation strategy seemed to open new perspectives in the creation of compounds whose direct synthesis was not yet achieved.

Reported by

University of Edinburgh
Old College South Bridge
EH1 1HN Edinburgh
United Kingdom
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