Toward control of gold cluster aggregation on TiO(2) via surface treatments

Published: October 1, 2015Well-defined Au–TiO₂ materials were synthesized by deposition of triphenylphosphine-protected Au₉ clusters on TiO₂ (Aeroxide P-25), pre-treated in eight different ways and subsequently exposed to two post-treatments. X-ray photoelectron spectroscopy and UV–vis diffuse reflectance spectroscopy studies showed that in most cases the PPh₃ ligand shell was removed upon deposition even before post-treatment, coinciding with some cluster aggregation. However, clusters deposited on TiO₂ treated using H₂SO₄ and H2O₂ showed remarkable resistance to aggregation, even after high-temperature calcination, while clusters on H₂-treated TiO₂ showed the greatest resistance to aggregation under ozonolysis.Jan-Yves Ruzicka, Faridah Abu Bakar, Christoffer Hoeck, Rohul Adnan, Campbell McNicoll, Tim Kemmitt, Bruce C. Cowie, Gregory F. Metha, Gunther G. Andersson, and Vladimir B. Golovk

Tumour regression and improved gastrointestinal tolerability from controlled release of SN-38 from novel polyoxazoline-modified dendrimers

Irinotecan is used clinically for the treatment of colorectal cancer; however, its utility is limited by its narrow therapeutic index. We describe the use of a generation 5 l-lysine dendrimer that has been part-modified with a polyoxazoline as a drug delivery vehicle for improving the therapeutic index of SN-38, the active metabolite of irinotecan. By conjugating SN-38 to the dendrimer via different linker technologies we sought to vary the release rate of the drug to generate diverse pharmacokinetic profiles. Three conjugates with plasma release half-lives of 2.5 h, 21 h, and 72 h were tested for efficacy and toxicity using a mouse SW620 xenograft model. In this model, the linker with a plasma release half-life of 21 h achieved sustained SN-38 exposure in blood, above the target concentration. Control over the release rate of the drug from the linker, combined with prolonged circulation of the dendrimer, enabled administration of an efficacious dose of SN-38, achieving significant regression of the SW620 tumours. The conjugates with 2.5 and 72 h release half-lives did not achieve an anti-tumour effect. Intraperitoneal dosing of the clinically used prodrug irinotecan produces high initial and local concentrations of SN-38, which are associated with gastrointestinal toxicity. Administration of the 21 h release dendrimer conjugate did not produce a high initial Cmax of SN-38. Consequently, a marked reduction in gastrointestinal toxicity was observed relative to irinotecan treatment. Additional studies investigating the dose concentrations and dose scheduling showed that a weekly dosing schedule of 4 mg SN-38/kg was the most efficacious regimen. After 4 doses at weekly intervals, the survival period of the mice extended beyond 70 days following the final dose. These extensive studies have allowed us to identify a linker, dose and dosing regimen for SN-38 conjugated to polyoxazoline-modified dendrimer that maximised efficacy and minimised adverse side effects

Cost efficient preparation of lead aminoalkoxides directly from lead(II) oxide

The prepn. of lead(II) aminoalkoxides has been demonstrated from the direct reaction of aminoalcs. with lead(II) oxide. The denticity of the aminoalcs. detd. the facility of the reactions, the rate increasing with the no. of hydroxyls. Thus, [Pb(dmae)2], 1, [Pb(mdea)]/, 2, and [Pb(teaH)]2, 3 (dmaeH = dimethylaminoethanol, mdeaH2 = N-methyldiethanolamine, and teaH3 = triethanolamine) have been prepd. in high yields and characterized by 1H and 13C NMR. The X-ray crystal structure analyses of 2 and 3 are described