Influence of pyridine versus piperidine ligands on the chemical, DNA binding and cytotoxic properties of light activated trans,trans,trans-[Pt(N3)2(OH)2(NH3)(L)]

The photocytotoxicity and photobiochemical properties of the new complex trans, trans, trans-[Pt(N3)2(OH)2(NH3)(piperidine)] (5) are compared with its analogue containing the less basic and less lipophilic ligand pyridine (4). The log P (n-octanol/water) values were of -1.16 and -1.84 for the piperidine and pyridine complexes, respectively, confirmed that piperidine increases the hydrophobicity of the complex. DFT and TDDFT calculations indicate that 5 has accessible singlet and triplet states which can promote ligand dissociation when populated by both UVA and visible white light. When activated by UVA or white light, both compounds showed similar cytotoxic potencies in various human cancer cell lines although their selectivity was different. The time needed to reach similar antiproliferative activity was noticeably decreased by introducing the piperidine ligand. Neither compound showed cross-resistance in three oxoplatin-resistant cell lines. Furthermore, both compounds showed similar anticlonogenic activity when activated by UVA radiation. Interactions of the light-activated complexes with DNA showed similar kinetics and levels of DNA platination and similar levels of DNA interstrand cross-linking (ca. 5 %). Also the ability to unwind double stranded DNA where comparable for the piperidine analogue (24°, respectively), while the piperidine complex showed higher potency in changing the conformation of DNA, as measured in an ethidium bromide binding assay. These results indicate that the nature of the heterocyclic nitrogen ligand can have subtle influences on both the phototoxicity and photobiochemistry of this class of photochemotherapeutic agents

Influence of the Formulation Process in Electrostatic Assembly of Nanoparticles and Macromolecules in Aqueous Solution: The Mixing Pathway

The influence of formulation process/pathway on the generation of electrostatically coassembled complexes made from polyelectrolyte-neutral copolymers and oppositely charged nanocolloids is investigated in this work. Under strong driving forces like electrostatic interaction and/or hydrogen bonding, the key factor controlling the polydispersity and the final size of the complexes is the competition between the reaction time of the components and the homogenization time of the mixed solution. The former depends on the initial concentration of the individual stock solutions and the nature of the interaction and will be investigated in a forthcoming publication; the latter depends on the mixing pathway and is put under scrutiny here on a system composed of cerium oxide nanoparticles and charged-neutral diblock copolymers (CeO2/PSS7K-b- PAM30K) by tuning the mixing order and/or speed. The resulting structures generated from various formulation processes were characterized by light and neutron scattering techniques. The complexes final morphologies (size, shape, polydispersity) were found to depend strongly on the formulation process, while keeping at a smaller scale (clusters) the same nanostructure. Finally, the impact of those different structures on some bulk (rheology) and surface (wetting/antifouling) properties was evaluated. These results highlighted that a process dependent formulation seen a priori as a drawback can be turned into an advantage: different properties can be developed from different morphologies while keeping the chemistry constant