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Within this work we aimed to improve the pharmacodynamics and toxicity profile of organoruthenium and -rhodium complexes which had previously been found to be highly potent in vitro but showed unselective activity in vivo. Different organometallic complexes were attached to a degradable poly(organo)phosphazene macromolecule, prepared via controlled polymerization techniques. The conjugation to hydrophilic polymers was designed to increase the aqueous solubility of the typically poorly soluble metal-based half-sandwich compounds with the aim of a controlled, pH-triggered release of the active metallodrug. The synthesized conjugates and their characteristics have been thoroughly studied by means of 31P NMR and UV-Vis spectroscopy, ICP-MS analyses and SEC coupled to ICP-MS. In order to assess their potential as possible anticancer drug candidates, the complexes, as well as their respective macromolecular prodrug formulations were tested against three different cancer cell lines in cell culture. Subsequently, the anticancer activity and organ distribution of the poly(organo)phosphazene drug conjugates were explored in vivo in mice bearing CT-26 colon carcinoma. Our investigations revealed a beneficial influence of this macromolecular prodrug by a significant reduction of adverse effects compared to the free metallodrugs. [ABSTRACT FROM AUTHOR]

Poly(organo)phosphazenes are a family of inorganic molecular hybrid polymers with very diverse properties due to the vast array of organic substituents possible. This tutorial review aims to introduce the basics of the synthetic chemistry of polyphosphazenes, detailing for readers outside the field the essential knowledge required to design and prepare polyphosphazenes with desired properties. A particular focus is given to some of the recent advances in their chemical synthesis which allows not only the preparation of polyphosphazenes with controlled molecular weights and polydispersities, but also novel branched architectures and block copolymers. We also discuss the preparation of supramolecular structures, bioconjugates and in situ forming gels from this diverse family of functional materials. This tutorial review aims to equip the reader to prepare defined polyphosphazenes with unique property combinations and in doing so we hope to stimulate further research and yet more innovative applications for these highly interesting multifaceted materials. [ABSTRACT FROM AUTHOR]

The pharmacologically active [Ru(CO)3Cl(glycinate)] is shown to be in equilibrium with [Ru(CO)2(CO2H)Cl(glycinate)]- (isomers) at around pH 3.1 which then at physiological pH reacts with more base to give [Ru(CO)2(CO2)Cl(glycinate)]2- (isomers) or [Ru(CO)2(CO2H)(OH)(glycinate)]-(isomers). The ease with which [Ru(CO)3Cl(glycinate)] reacts with hydroxide results in it producing a solution in water with a pH of around 2 to 2.5 depending on concentration and making its solutions more acidic than those of acetic acid at comparable concentrations. Acidification of [Ru(CO)3Cl(glycinate)] with HCl gives [Ru(CO)3Cl2(NH2CH2CO2H)]. The crystal structures of [Ru(CO)3Cl(glycinate)] and [Ru(CO)3Cl2(NH2CH2CO2Me)] are reported. [ABSTRACT FROM AUTHOR]

Within this work we aimed to improve the pharmacodynamics and toxicity profile of organoruthenium and -rhodium complexes which had previously been found to be highly potent in vitro but showed unselective activity in vivo. Different organometallic complexes were attached to a degradable poly(organo)phosphazene macromolecule, prepared via controlled polymerization techniques. The conjugation to hydrophilic polymers was designed to increase the aqueous solubility of the typically poorly soluble metal-based half-sandwich compounds with the aim of a controlled, pH-triggered release of the active metallodrug. The synthesized conjugates and their characteristics have been thoroughly studied by means of 31 P NMR and UV-Vis spectroscopy, ICP-MS analyses and SEC coupled to ICP-MS. In order to assess their potential as possible anticancer drug candidates, the complexes, as well as their respective macromolecular prodrug formulations were tested against three different cancer cell lines in cell culture. Subsequently, the anticancer activity and organ distribution of the poly(organo)phosphazene drug conjugates were explored in vivo in mice bearing CT-26 colon carcinoma. Our investigations revealed a beneficial influence of this macromolecular prodrug by a significant reduction of adverse effects compared to the free metallodrugs.

The pharmacologically active [Ru(CO)(3)Cl(glycinate)] is shown to be in equilibrium with [Ru(CO)(2)(CO(2)H)Cl(glycinate)](-) (isomers) at around pH 3.1 which then at physiological pH reacts with more base to give [Ru(CO)(2)(CO(2))Cl(glycinate)](2-) (isomers) or [Ru(CO)(2)(CO(2)H)(OH)(glycinate)](-) (isomers). The ease with which [Ru(CO)(3)Cl(glycinate)] reacts with hydroxide results in it producing a solution in water with a pH of around 2 to 2.5 depending on concentration and making its solutions more acidic than those of acetic acid at comparable concentrations. Acidification of [Ru(CO)(3)Cl(glycinate)] with HCl gives [Ru(CO)(3)Cl(2)(NH(2)CH(2)CO(2)H)]. The crystal structures of [Ru(CO)(3)Cl(glycinate)] and [Ru(CO)(3)Cl(2)(NH(2)CH(2)CO(2)Me)] are reported.