title: Low toxicity β-cyclodextrin-caged 4,4'-bipyridinium-bis(siloxane): synthesis and evaluation.
abstract: The toxicity of viologens can be significantly reduced by including them in tight [2]rotaxane structures alongside β-cyclodextrin, thus turning them into candidates of pharmaceutical interest. Here, we report a synthesis pathway for a benign viologen, by capping a small β-cyclodextrin-caged molecule, the 4,4'-bipyridine, with minimal-length presynthesized axle-stopper segments of the propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to laboratory mice, the product concentration in the bloodstream reaches a value equivalent to 0.634% of the initial dose of 800 mg·kg(-1). As compared to the nude viologen having the same structure, which proved to be lethal in doses of 40 mg·kg(-1), the product induces reversible morphological changes in the liver, kidney, lung, and cerebellum, up to a dose of 400 mg·kg(-1), with higher dosages giving rise to a chronic slow evolution.
authors.affiliation: Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry of Romanian Academy , Iasi 700487, Romania.
authors.forename: Narcisa
authors.initials: N
authors.lastname: Marangoci
authors.forename: Stelian S
authors.initials: SS
authors.lastname: Maier
authors.forename: Rodinel
authors.initials: R
authors.lastname: Ardeleanu
authors.forename: Adina
authors.initials: A
authors.lastname: Arvinte
authors.forename: Adrian
authors.initials: A
authors.lastname: Fifere
authors.forename: Anca Roxana
authors.initials: AR
authors.lastname: Petrovici
authors.forename: Alina
authors.initials: A
authors.lastname: Nicolescu
authors.forename: Valentin
authors.initials: V
authors.lastname: Nastasa
authors.forename: Mihai
authors.initials: M
authors.lastname: Mares
authors.forename: Sorin A
authors.initials: SA
authors.lastname: Pasca
authors.forename: Ramona F
authors.initials: RF
authors.lastname: Moraru
authors.forename: Mariana
authors.initials: M
authors.lastname: Pinteala
authors.forename: Anca
authors.initials: A
authors.lastname: Chiriac
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002531:Cerebellum / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D051379:Mice; D066244:Proton Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000737:chemistry / Q000633:toxicity*; D012833:Siloxanes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D011725:Pyridines; D012833:Siloxanes; D047392:beta-Cyclodextrins; C031215:betadex; C034306:4,4'-bipyridyl