TY - JOUR
T1 - Chiral pH-sensitive cyclobutane beta-amino acid-based cationic amphiphiles
T2 - Possible candidates for use in gene therapy
AU - Pi-Boleda, Bernat
AU - Bouzas, Mireia
AU - Gaztelumendi, Nerea
AU - Illa, Ona
AU - Nogués, Carme
AU - Branchadell, Vicenç
AU - Pons, Ramon
AU - Ortuño, Rosa M.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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. (C) 2018 Elsevier B.V. All rights reserved.
AB - 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. (C) 2018 Elsevier B.V. All rights reserved.
KW - DENSITY-FUNCTIONAL THEORY
KW - CIS/TRANS STEREOCHEMISTRY
KW - GEMINI SURFACTANTS
KW - AGGREGATION
KW - TRANSFECTION
KW - TRANSITION
KW - TITRATION
KW - MICELLES
KW - BROMIDE
KW - SYSTEMS
UR - http://www.scopus.com/inward/record.url?scp=85075529427&partnerID=8YFLogxK
U2 - 10.1016/j.molliq.2019.111856
DO - 10.1016/j.molliq.2019.111856
M3 - Article
AN - SCOPUS:85075529427
VL - 297
JO - Journal of Molecular Liquids
JF - Journal of Molecular Liquids
SN - 0167-7322
M1 - 111856
ER -