title: Enhancing the antioxidant characteristics of phenolic acids by their conversion into cholinium salts.
abstract: Due to the close relation between oxidative stress and a plethora of inflammatory diseases, antioxidants have received an increased attention for incorporation into dermatological products. Their use and absorption is however limited by their low solubility in water-rich formulations. Herein, a set of novel cholinium-based salts, namely dicholinium ellagate and cholinium caffeate, syringate, vanillate, gallate and salicylate were synthetized and characterized. Their melting and decomposition temperatures, water solubility, and toxicological, antioxidant, cytotoxicity and pro-/anti-inflammatory activities were addressed. These new salts, exclusively composed of ions derived from natural sources, display a high thermal stability - up to 150 ºC. The synthesized compounds are significantly more soluble in water (in average, 3 orders of magnitude higher) than the corresponding phenolic acids. Furthermore, they present not only similar but even higher antioxidant and anti-inflammatory activities, as well as comparable cytotoxicity and lower ecotoxicity profiles than their acidic precursors. Amongst all the investigated salts, dicholinium ellagate is the most promising synthesized salt when considering the respective antioxidant and anti-inflammatory activities. Since all the synthesized salts are based on the cholinium cation, they can further be envisaged as essential nutrients to be used in oral drugs.
authors.affiliation: CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Tânia E
authors.initials: TE
authors.lastname: Sintra
authors.affiliation: CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Luís
authors.affiliation: CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Rocha
authors.affiliation: CIQUP, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
authors.forename: Ana I M C
authors.initials: AI
authors.lastname: Lobo Ferreira
authors.affiliation: CESAM, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gonçalves
authors.affiliation: CIQUP, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
authors.forename: Luís M N B F
authors.initials: LM
authors.lastname: Santos
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; Centre for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Neves
authors.affiliation: CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Mara G
authors.initials: MG
authors.lastname: Freire
authors.affiliation: CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sónia P M
authors.initials: SP
authors.lastname: Ventura
authors.affiliation: CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: João A P
authors.initials: JA
authors.lastname: Coutinho
keywords: Antioxidant salts; anti-inflammatory activity; cytotoxicity; ecotoxicity; solubility