Synthesis, Characterization, and Applications of Hemifluorinated Dibranched Amphiphiles

• Published in: Journal of organic chemistry 2011-08, Vol.76 (16), p.6584-6591
• Main Authors: Parlato, Maria Cristina, Jee, Jun-Pil, Teshite, Motti, Mecozzi, Sandro
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Chemistry; Colloidal state and disperse state; Emulsions; Exact sciences and technology; General and physical chemistry; Hydrocarbons, Fluorinated - chemical synthesis; Hydrocarbons, Fluorinated - chemistry; Hydrophobic and Hydrophilic Interactions; Methyl Ethers - chemistry; Micelles; Micelles. Thin films; Organic chemistry; Polymers - chemistry; Preparations and properties; Silica Gel - chemistry; Solubility; Surface Properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo200835y

Here we describe the synthesis and the physicochemical and preliminary pharmaceutical assessment of a novel class of hemifluorinated dibranched derivatives: M1diH x F y . These compounds have the remarkable ability to completely stop the Ostwald ripening commonly associated with nanoemulsions. The developed synthesis is modular and allows easy incremental structural variations in the fluorophilic (fluorous chains), lipophilic (alkyl spacer head), and hydrophilic (polar head) domains. Furthermore, the synthesis can be easily scaled up and highly pure compounds can be readily obtained through silica gel and fluoro-silica gel column chromatography, without any need to use HPLC or other time-consuming techniques. Surface properties such as micelle formation, critical aggregation concentration (CAC), and emulsion stability studies demonstrated the different behavior of the dibranched hemifluorinated surfactant M1diH x F y with respect to that of single-chain semifluorinated analogues M z F y . Remarkably, the new polymer M1diH3F8 drastically slowed the ripening of nanoemulsions of the commonly used fluorinated anesthetic sevoflurane over a period of more than 1 year. During this time, the nanodroplet size did not increase to more than 400 nm. This result is very promising for inducing and maintaining general anesthesia through intravenous delivery of volatile anesthetics, eliminating the need for the use of large and costly vaporizers in the operating room.