Cholinium-based ionic liquids with pharmaceutically active anions

Araújo, João M. M.; Florindo, Catarina; Pereiro, Ana B.; Vieira, Nicole S. M.; Matias, Ana A.; Duarte, Catarina M.M.; Rebelo, Luís Paulo N.; Marrucho, Isabel M.

doi:10.1039/c3ra47615d

Cited by 97 publications

(88 citation statements)

References 60 publications

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“…19 All these procedures are described in the Electronic Supporting Information (ESI). Purity was checked by 1 H and 19 F NMR as well as by Elemental Analysis and electrospray ionisation mass spectra (ESI-MS).…”

Section: Experimental Methodsmentioning

confidence: 99%

A thermophysical and structural characterization of ionic liquids with alkyl and perfluoroalkyl side chains

et al. 2015

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This work represents an essential step towards the understanding of the dynamics and thermodynamic characteristics of a novel family of ionic liquids, namely fluorinated ionic liquids based on the combination of 1-alkyl-3-methylimidazolium cations with perfluoroalkylsulfonates or perfluoroalkylcarboxylates anions. The so far scarce information about these fluids constitutes a limiting factor for their potential applications. In this work, we provide detailed evidence on the influence of hydrogenated and fluorinated alkyl chain lengths in the final characteristics of the fluorinated ionic liquids. Different properties, namely, melting point, decomposition temperature, density, dynamic viscosity, ionic conductivity and refractive index, were determined and the experimental results were discussed taking into account the influence of the length of the hydrogenated and fluorinated alkyl chains. Molecular dynamic simulations were also performed to study the nanoscale structuration of these novel compounds. Electronic Supplementary Information (ESI) available: The ESI contains the synthesis and characterization of novel FILs and experimental data of thermal properties, density, viscosity, refractive index and ionic conductivity. Moreover, the fitting parameters of these properties and values of molar volume and molar refraction are also showed. See

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Section: Experimental Methodsmentioning

confidence: 99%

A thermophysical and structural characterization of ionic liquids with alkyl and perfluoroalkyl side chains

et al. 2015

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“…[16] In the field of pharmaceutical sciences,w ea nd others have reported that the cation-anion interactions in the prepared API-ILs induce improved physicochemical properties over the original drugs, decrease toxicityt oward healthyc ells, and thus render potentially enhanced pharmaceutical activity to the API. [17][18][19][20][21][22] In more detail,s uch combinations boost the stability and solubility of the API in physiological media, changing its pharmacokinetics and delivery mode. [23][24][25][26][27] Hence, the biopharmaceutics drug classification systemf or API-ILs can be significantly modified in comparison with their respective parentdrugs,meaning that the new organic salt of an old API can be treated as a new chemical entity,a nd thus be independently patented.…”

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confidence: 99%

Ionic Liquids and Salts from Ibuprofen as Promising Innovative Formulations of an Old Drug

et al. 2019

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Herein we report the synthesis of novel ionic liquids( ILs) and organic salts by combining ibuprofen as anion with ammonium, imidazolium, or pyridinium cations. The methodology consists of an acid-base reactiono fn eutral ibuprofen with cation hydroxides, which were previouslyp repared by anion exchange from the correspondingh alide salts with Amberlyst A-26(OH). In comparison with the parent drug, these organic salts display higher solubility in water and biological fluids and as maller degree of polymorphism, which in some cases was completely eliminated. With the exceptiono f [ C 16 Pyr][Ibu] and [N 1,1,2,2OH1 ][Ibu],t he prepared salts did not affect the viabilityo f normalh uman dermalf ibroblasts or ovarian carcinoma (A2780) cells. Therefore, these ibuprofen-based ionic liquids may be very promising lead candidates for the development of effective formulationso ft his drug.Ibuprofen is used in the treatmento fp aina nd inflammation in rheumatoid arthritisa nd other musculoskeletal disorders in both humans and animals. [1] It is considered one of the Essential Medicines by the World Health Organization( WHO). Ibuprofen is an onsteroidal anti-inflammatory drug (NSAID), which nonselectively inhibits cyclooxygenases 1a nd 2( COX-1a nd COX-2), resulting in the inhibition of prostaglandins. [2] Althoughi th as as trongera nalgesice ffect than other NSAIDs in some types of pain, [3] the mean onset of action per 400 mg dose is 45 minutes, which can be critical in an acute painsituation, where rapid relief is critical. [4] Its low solubility in the acidic aqueous media of the stomach is responsible for ibuprofen'ss low pharmaceutical effect, [5] despite its ease of permeability through the gastrointestinal membranes, rendering close to 100 %b ioavailability. [6] To increase the absorption rate and to provide faster pain relief, new formulations of ibuprofen have been developed over the years, particularly salts (sodium, [7] lysine, [8] and arginine [9] )a nd extrudate. [10] These forms, however,d on ot tackle the degree of ibuprofen's poly-morphism, [11] whose different crystal shapes display distinct pharmaceutical effects.For the last 10 years, ionic liquids (ILs) from active pharmaceuticali ngredients (APIs), or simply API-ILs, have been studied at the academic level, as the third generation of ILs. [12][13][14][15] ILs are salts with meltingt emperatures below 100 8C, with some of them being liquid at room temperature (RTILs), that result from the combinationoforganic cations with organic and inorganic anions. The scope of their physicala nd chemical properties has promptedt he study and application of these compounds in several areas of science and technology. [16] In the field of pharmaceutical sciences,w ea nd others have reported that the cation-anion interactions in the prepared API-ILs induce improved physicochemical properties over the original drugs, decrease toxicityt oward healthyc ells, and thus render potentially enhanced pharmaceutical activity to the API. [17][18][19][20][21][22] In more detail,s u...

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“…Early advances were motivated to develop ILs as green, nonvolatile, nonflammable, and stable solvents, however, recent findings have broadened the field, redefining ILs as low melting salts (melting point <100°C) with an unlimited suite of tunable properties including toxicity, volatility, flammability, and instability . The erstwhile narrow perspective that views ILs as salts of quaternary ammonium, imidazolium, pyrrolidinium, pyridinium, or phosphonium cations has broadened as new cations including the bioinspired cholinium and guanidinium cations as well as metal‐containing cations are paired with various anions to afford salts that meet the definition of IL (Figure ). The evolving complexity of the precursors fosters a conjecture that explains their characteristically low melting point by the structural heterogeneity of a sterically hindered asymmetric cation that impedes strong ionic interaction with the anion as well as precludes ordered packing within a crystal lattice.…”

Section: Introductionmentioning

confidence: 99%

“…Also, by coupling cholinium with pharmaceutically active anions, the Marrucho group advanced the physicochemical and pharmaceutical properties of the anions . Specifically, API‐ILs derived by combining cholinium with anions of nalidixic acid, niflumic acid, 4‐aminosalicylic acid, pyrazinoic acid, or picolinic acid exhibit better solubility in water, gastric, and intestinal fluid . Enhanced solubility is presumed to boost membrane permeability, increasing bioavailability and eventually therapeutic efficacy but could lead to over‐dosage that is detrimental to critical cellular processes.…”

Section: Introductionmentioning

confidence: 99%

Ionic liquids for addressing unmet needs in healthcare

Agatemor¹,

Ibsen²,

Tanner³

et al. 2018

Bioengineering & Transla Med

135

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Advances in the field of ionic liquids have opened new applications beyond their traditional use as solvents into other fields especially healthcare. The broad chemical space, rich with structurally diverse ions, and coupled with the flexibility to form complementary ion pairs enables task‐specific optimization at the molecular level to design ionic liquids for envisioned functions. Consequently, ionic liquids now are tailored as innovative solutions to address many problems in medicine. To date, ionic liquids have been designed to promote dissolution of poorly soluble drugs and disrupt physiological barriers to transport drugs to targeted sites. Also, their antimicrobial activity has been demonstrated and could be exploited to prevent and treat infectious diseases. Metal‐containing ionic liquids have also been designed and offer unique features due to incorporation of metals. Here, we review application‐driven investigations of ionic liquids in medicine with respect to current status and future potential.

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Cholinium-based ionic liquids with pharmaceutically active anions

Cited by 97 publications

References 60 publications

A thermophysical and structural characterization of ionic liquids with alkyl and perfluoroalkyl side chains

A thermophysical and structural characterization of ionic liquids with alkyl and perfluoroalkyl side chains

Ionic Liquids and Salts from Ibuprofen as Promising Innovative Formulations of an Old Drug

Ionic liquids for addressing unmet needs in healthcare

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