Pyridinium lipids with the dodecaborate cluster as polar headgroup: synthesis, characterization of the physical-chemical behavior, and toxicity in cell culture.
We have prepared nine new dodecaborate cluster lipids with potential use in boron neutron capture therapy of tumors. This new generation of boron lipids is only singly negatively charged and consists of a pyridinium core with C(12), C(14), and C(16) chains as lipid backbone, connected through the nitrogen atom via a butylene, pentylene, or ethyleneoxyethylene linker to the oxygen atom on the dodecaborate cluster as headgroup. The lipids were obtained by nucleophilic attack of 4-(bisalkylmethyl)pyridine on the tetrahydrofurane, the dioxane, and a newly prepared tetrahydropyrane derivative, respectively, of closo-dodecaborate. All of these boron lipids are able to form closed vesicles in addition to some bilayers in the pure state and in the presence of helper lipids. The thermotropic behavior was found to be increasingly complex and polymorphic with increasing alkyl chain length. Except for two lipids, all lipids have low in vitro toxicity, and longer alkyl chains lead to a significant decrease in toxicity. The choice of the linker plays no major role with respect to their ability to form liposomes and their thermotropic properties, but the toxicity is influenced by the linkers in the case of short alkyl chains.
Schaffran
Tanja
T
Department of Chemistry, University of Bremen, P.O. Box 330440, D-28357 Bremen. T.Schaffran@web.de
Burghardt
Alexander
A
Barnert
Sabine
S
Peschka-Süss
Regine
R
Schubert
Rolf
R
Winterhalter
Mathias
M
Gabel
Detlef
D
D000818:Animals; D001896:Boron Compounds / Q000737:chemistry* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D008081:Liposomes / Q000737:chemistry; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D001896:Boron Compounds; D008055:Lipids; D008081:Liposomes; D011725:Pyridines; C119788:dodecaborate