Chiral pH-sensitive cyclobutane beta-amino acid-based cationic amphiphiles : Possible candidates for use in gene therapy
Pi i Boleda, Bernat (Universitat Autònoma de Barcelona. Departament de Química)
Bouzas, Mireia (Universitat Autònoma de Barcelona. Departament de Química)
Gaztelumendi, Nerea (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Illa, Ona (Universitat Autònoma de Barcelona. Departament de Química)
Nogués, C. (Carme) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Branchadell Gallo, Vicenç (Universitat Autònoma de Barcelona. Departament de Química)
Pons, Ramon (Institut de Química Avançada de Catalunya. Departament de Tensioactius i Nanobiotecnologia)
Ortuño Mingarro, Rosa María (Universitat Autònoma de Barcelona. Departament de Química)

Data:	2020
Resum:	Chiral cis/trans diastereomeric cationic amphiphiles have been synthesized and studied. They are based on beta-amino acids and contain C-12- and C-16-alkyl chains, respectively, as hydrophobic tails while the polar head consists of an ammonium cation linked to a cyclobutane ring. Their physicochemical properties, such as the cmc (critical micellar concentration), the pK(a), the ratio of cationic versus non-ionic species, and the surface tension are strongly dependent on the pH of the medium. At the same time the aggregation state influences on the apparent pK(a) values of the aggregates, with release of protons at the cmc whose values, as well as those of the adsorption effectiveness, account for their efficient surfactant behavior. A tail-length effect is manifest because surfactant cmc of compounds with a C-16-alkyl chain are smaller than the C-12-ones, although not as small as expected. On the other hand, while for C-12-surfactants the role of the stereochemistry on the physicochemical parameters is patent, it is not very clear for C-16-surfactants. The stereochemistry also determines the predominant mode of self-assembly since the trend for cis-isomers is to form micelles or vesicles while trans-isomers preferably form fibers. CD spectroscopy confirmed the aggregation through the formation of intermolecular hydrogen bonds between the amide groups of the monomers. An alternative method to determine the cmc of these surfactants is provided by considering the relationship of the CD lambda(max) with concentration, although it is restricted to those surfactants in which the chromophore is located in a chiral environment. Furthermore, the non- toxicity of the surfactants has been verified by the MTT assay. This characteristic, jointly with the efficiency and the good properties shown, the fact that the cationic species are present in a high concentration at physiological pH, as well as the weak acid behavior of the aggregates, confirm these amphiphiles as promising candidates to be used as non-viral vectors for gene therapy applications.
Ajuts:	Ministerio de Economía y Competitividad CTQ2016-77978-R Agencia Estatal de Investigación CTQ2017-88948-P
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Density-Functional Theory ; Cis/Trans Stereochemistry ; Gemini Surfactants ; Aggregation ; Transfection ; Transition ; Titration ; Micelles ; Bromide ; Systems
Publicat a:	Journal of Molecular Liquids, Vol. 297 (January 2020) , art. 111856, ISSN 1873-3166

DOI: 10.1016/j.molliq.2019.111856

Postprint 31 p, 920.4 KB

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