Encyclopedia of Ionic Liquids

Living Edition
| Editors: Suojiang Zhang

Aquatic Toxicology of Ionic Liquids (ILs)

  • Francisca A. e Silva
  • João A. P. Coutinho
  • Sónia P. M. VenturaEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-981-10-6739-6_52-1

Introduction

The broad application of ionic liquids (ILs) as process chemicals, solvents, heat transfer and storage fluids, electrolytes, and additives is encouraging significant progress in the design of novel chemical and biotechnological processes and products [1]. Both academia and industry have been using ILs to boost established processes including laborious routes, replace nefarious chemicals, or minimize waste generation, as well as create innovative technologies and products [1, 2, 3]. What made ILs appealing was, in the first place, their recognized unique physical and chemical properties (e.g., non-flammability, nonvolatility, high thermal stability, solvation ability, and structural versatility) [4]. Together with their “designer solvent” status, ILs started to be defined as “green” and, more recently, “high performance” chemicals [5, 6]. Often, however, such headlines represent nothing but overgeneralizations that lead to critical misconceptions within IL field. Likely, the most controversial IL classification is that of “green solvent”. Even though ILs’ nonvolatility prevents the risk of atmospheric pollution – a plus over common volatile organic solvents – their water solubility makes them prone to enter and impact on aquatic ecosystems. ILs are not inherently green, since most of them possess equivalent or even higher toxicity than traditional organic solvents [7]. At the current stage, where ILs play an expanding role in industry [1, 2], they must be regarded as emerging contaminants [8], and the full disclosure of their aquatic toxicology is imperative.

Efforts have been made along the years to clarify the toxic action of ILs over aquatic organisms. As reviewed [7, 9, 10], the set of published works follow at least one of three core strategies: (i) assessing structure-ecotoxicity relationships by changing the cation, anion, and respective alkyl chain lengths and functionalized groups; (ii) covering multitrophic bioassays, through distinct types of toxicity tests (e.g., acute toxicity and Microtox – undoubtedly the most studied – but also chronic, reproductive, and embryo toxicity); and (iii) attesting the environmental benignity of ILs designed for a specific application.

In general, the results collected so far reveal that the ILs’ hazard potential can range from low to high, being mainly dependent on the cation and anion chemical structures and the aquatic organism considered. Table 1 provides a description of the battery of tests commonly used to assess the aquatic toxicity of ILs. Moreover, the European categories for hazardous substances over the aquatic organisms (i.e., fish, Crustacea, and algae/other aquatic plants) considered for IL toxicology studies (acute, short-term) are compiled to help characterize the ecotoxic effects reported on this entry [11].
Table 1

Battery of tests commonly used to assess the aquatic toxicity of ILs

Trophic level

Test

Endpoint

Toxicity parameter

Duration (acute toxicity)

Toxicity categories [11]

Decomposer

Marine luminescent bacteria: Aliivibrio fischeri

Luminescence inhibition

ECx (IL concentration that yields x% loss of luminescence)

5–30 min

Bacteria are not considered by the European classification

Primary producers

Green algae: Raphidocelis subcapitata

Scenedesmus sp.

Growth inhibition

ECx (IL concentration that yields x% growth inhibition)

24–72 h

“Acute 1”: 72 h EC50 ≤1 mg L−1

“Acute 2”: 72 h EC50 >1 mg L−1 but ≤10 mg L−1

“Acute 3”: 72 h EC50 >10 mg L−1 but ≤100 mg L−1

Duckweeds: Lemna minor

Growth inhibition

ECx (IL concentration that yields x% growth inhibition)

96 h

“Acute 1”: 96 h EC50 ≤1 mg L−1

“Acute 2”: 96 h EC50 >1 mg L−1 but ≤10 mg L−1

“Acute 3”: 96 h EC50 >10 mg L−1 but ≤100 mg L−1

Primary consumers

Freshwater crustaceans: Daphnia magna

Immobility

ECx (IL concentration that yields x% loss of mobility)

24–48 h

“Acute 1”: 48 h EC50 ≤1 mg L−1

“Acute 2”: 48 h EC50 >1 mg L−1 but ≤10 mg L−1

“Acute 3”: 48 h EC50 >10 mg L−1 but ≤100 mg L−1

Saltwater crustaceans: Artemia salina (brine shrimp)

Hatchability, mortality

Hatchability, % (number of larva per number of initial cysts)

LC50 (IL concentration that yields 50% deaths)

24–72 h

“Acute 1”: 48 h LC50 ≤1 mg L−1

“Acute 2”: 48 h LC50 >1 mg L−1 but ≤10 mg L−1

“Acute 3”: 48 h LC50 >10 mg L−1 but ≤100 mg L−1

 

Freshwater mollusc: Physa acuta (freshwater snail)

Hatchability, mortality

Mortality, % (number of dead embryos per number of total embryos); hatchability, % (number of hatched larva per number of total embryos); LC50 (IL concentration that yields 50% deaths)

96 h

Molluscs are not considered by the European classification

Secondary consumers

Fishes: Danio rerio (zebra fish)

Mortality, locomotion, hatchability

LC50 (IL concentration that yields 50% deaths) hatchability, % (number of hatching embryos per number of remaining embryos)

24–96 h

“Acute 1”: 96 h LC50 ≤1 mg L−1

“Acute 2”: 96 h LC50 >1 mg L−1 but ≤10 mg L−1

“Acute 3”: 96 h LC50 >10 mg L−1 but ≤100 mg L−1

General guidelines to help defining the sustainable design of ILs are currently available [7, 9, 10]. The (eco)toxicity profiles instigated by the cation core nature, the anion moiety structure, and the introduction of aliphatic chains or functionalized groups are well-documented, although outliers may occur due to synergistic effects of the IL components and the aquatic organism tested. In earlier studies, major attention was given to nitrogen-based cyclic structures at the cation (e.g., 1-alkyl-3-butylimidazolium, [CnC1im]+; 1-alkyl-3-methylpyridinium, [CnC1pyr]+; 1-alkyl-1-methylpyrrolidinium, [CnC1pyrr]+; 1-alkyl-1-methylpiperidinium, [CnC1pip]+; and 4-alkyl-4-methylmorpholinium, [CnC1mor]+) and halogenated anions (e.g., bis(trifluoromethylsulfonyl)imide, [NTf2]; hexafluorophosphate, [PF6]; tetrafluoroborate, [BF4]; chloride, Cl; and bromide, Br). Currently, the database of ILs’ aquatic toxicity is much broader and includes quaternary ammonium (e.g., tetraalkylammonium, [Nwxyz]+; and cholinium, [N111(2OH)]+]), (e.g., di-alkyl-tetra-methyl-guanidinium, [CnCn(C1C1C1C1gua)]+) and phosphonium (e.g., tetraalkylphosphonium, [Pwxyz]+) cations as well as organic anions (e.g., alkanoates, [CnCO2]).

Within this body of data [7, 9, 10], it is now possible to define some heuristic rules considering the cation head group, anion moiety, alkyl side-chain elongation, and functionalization to anticipate the toxicity of an IL. The impact of the cation head group is driven by the water solubility and aromaticity of the IL. Phosphonium-based and nitrogen-based aromatic cations (e.g., [CnC1im]+ and [CnC1pyr]+) are more toxic than nitrogen-based cyclic (e.g., [CnC1pyrr]+, [CnC1pip]+, and [CnC1mor]+) and acyclic (e.g., [Cngua]+, [Nn444]+, and [N111(2OH)]+) ones. The patterns were consistent along distinct microorganisms/trophic levels, e.g., Vibrio fischeri now Aliivibrio fischeri (A. fischeri), Daphnia magna (D. magna), Raphidocelis subcapitata (R. subcapitata), and Physa acuta (P. acuta) [7, 9, 10]. The effect of the anion is less systematized. In general, fluorinated anions (e.g., [NTf2], [PF6], and [BF4]) are more toxic than halides (e.g., Cl and Br) due to their hydrophobicity what facilitates their interaction with cell membranes. The patterns were consistent along distinct trophic levels, e.g., D. magna, R. subcapitata, and Lemna minor (L. minor) [7, 9, 10]. The impact of the alkyl side-chain size is ruled by the hydrophobicity. The longer the alkyl side chains of either cation or anion, the higher the toxicity, i.e., “side-chain effect” (e.g., [CnC1im]+ or [CnCO2]). After a certain chain length, no further increment in toxicity seems to occur; this is known as the “cutoff effect”. These patterns were consistently observed along several cation/anion pairs and distinct trophic levels, e.g., D. magna, R. subcapitata, and A. fischeri [7, 9, 10]. Again, the hydrophobicity seems to rule the impact that the insertion of hydrophilic groups has on ILs’ ecotoxicity. The replacement of carbon by oxygen, chlorine, hydrogen, nitrile, and ether groups decreases the toxicity (e.g., [CnC1im]+) [7, 9, 10].

Taking into account the literature, this entry intends to summarize the progress made within the design of more sustainable ILs and overviews the importance of aquatic toxicology to guide such a task. In this context, cholinium-based ILs are being extensively studied in a large range of applications due to their claimed “green,” “biocompatible,” “benign,” or “nontoxic” nature, for which guidelines regarding structure-ecotoxicity relationships should be evaluated and future perspectives defined. A layout of the entry is provided in Fig. 1.
Fig. 1

Overview of the entry

Boosting the Sustainable Design of ILs

In the search for “greener” and more sustainable ILs, researchers have been implementing structures arising from natural and renewable feedstocks in the preparation of ILs [12]. Cholinium chloride, formally known as (2-hydroxyethyl)trimethylammonium chloride (further abbreviated as [N111(2OH)]Cl), is a naturally occurring essential nutrient relevant for the synthesis of vitamins and enzymes [13]. The incorporation of the cholinium core structure as an IL cation – [N111(2OH)]+ − has been envisaged as a “green”/more benign/biocompatible structure, a premise followed in the most recent years. Indeed, new literature is showing cholinium-based ILs as greener alternatives for the common nitrogen-based cyclic ILs (e.g., imidazolium-based). Initially, cholinium-based ILs were only approached as a common IL family in systematic studies of several fields (aquatic toxicology included) [14, 15, 16, 17]. Then, studies focusing the structure-ecotoxicity relationships appeared to elucidate the sustainable design of cholinium-based ILs, e.g., [18, 19, 20, 21] and those ionic structures started to be synthesized from other natural sources (e.g., amino acids) aiming to prepare more sustainable cholinium-based ILs [22, 23]. Taking into consideration the increasing focus given to these ionic compounds, cholinium-based ILs started to be evaluated in a large range of applications [24, 25, 26, 27], not just because they are allegedly “green” but as “high performance chemicals”. Figures 2 and 3 and Table 2 provide the chemical structures, name, and abbreviations of the cations and anions considered along aquatic toxicology studies of cholinium-based ILs reviewed in this work.
Fig. 2

Chemical structure of the cation in cholinium-based ILs

Fig. 3

Chemical structure of the anions in cholinium-based ILs

Table 2

Name and abbreviation of the cation-anion combinations in cholinium-based ILs

Cations

Anions

 

Name

Abbreviation

 

Name

Abbreviation

i

(2-Hydroxyethyl)trimethylammonium (cholinium)

[N111(2OH)]+

i

Chloride

Cl

ii

Benzyl(2-hydroxyethyl)dimethylammonium

[N11(C7H7)(2OH)]+

ii

Bromide

Br

iii

Alkyl(2-Hydroxyethyl)dimethylammonium

[N11n(2OH)]+

iii

Bis(trifluoromethylsulfonyl)imide

[NTf2]

iv

(2-Hydroxyethyl)dimethyl(2-propenyl)ammonium

[N11(3enyl)(2OH)]+

iv

Hexafluorophosphate

[PF6]

v

(2-Hydroxyethyl)dimethyl(2-propynyl)ammonium

[N11(3ynyl)(2OH)]+

v

Alkanoate

[CnCO2]

vi

Di(2-hydroxyethyl)propylammonium

[N03(2OH)(2OH)]+

vi

Dihydrogenphosphate

[H2PO4]

vii

Alkyldi(2-hydroxyethyl)methylammonium

[N1n(2OH)(2OH)]+

vii

Bicarbonate

[HCO3]

viii

Alkenyldi(2-hydroxyethyl)methylammonium

[N1(n enyl)(2OH)(2OH)]+

viii

Bitartrate

[Bit]

ix

Tri(2-hydroxyethyl)(2-propenyl)ammonium

[N(3enyl)(2OH)(2OH)(2OH)]+

ix

Dihydrogencitrate

[DHCit]

x

Hexyltri(2-hydroxyethyl)ammonium

[N6(2OH)(2OH)(2OH)]+

x

Glycinate

[Gly]

xi

N,N,N′,N′-Tetra(2-hydroxyethyl)-N,N′-dimethyl-1,n-alkyldiammonium

[N1(2OH)(2OH)-Cn-[N1(2OH)(2OH)]2+

xi

Alaninate

[Ala]

xii

N,N,N′,N′-Hexa(2-hydroxyethyl)-1,n-alkyldiammonium

[N(2OH)(2OH)(2OH)-Cn-[N(2OH)(2OH)(2OH)]2+

xii

Phenylalaninate

[Phe]

xiii

2-Hydroxyethylammonium

[N000(2OH)]+

xiii

Glutaminate

[Gln]

xiv

Di(2-hydroxyethyl)ammonium

[N00(2OH)(2OH)]+

xiv

Methionate

[Met]

xv

Tri(2-hydroxyethyl)ammonium

[N0(2OH)(2OH)(2OH)]+

xv

Argininate

[Arg]

   

xvi

Glutamate

[Glu]

   

xvii

Cystinate

[Cys-Cys]2−

   

xviii

Histidinate

[His]

   

xix

Prolinate

[Pro]

   

xx

Tryptophanate

[Trp]

   

xxi

Leucinate

[Leu]

   

xxii

Salicylate

[Sal]

   

xxiii

Ellagate

[Ell]2−

   

xxiv

Caffeate

[Caf]

   

xxv

Syringate

[Syr]

   

xxvi

Vanillate

[Van]

   

xxvii

Gallate

[Gal]

   

xxviii

Dodecylbenzenesulfonate

[DBS]

   

xxix

2-(N-Morpholino)ethanesulfonate

[MES]

   

xxx

N-[Tris(hydroxymethyl)methyl]glycinate

[Tricine]

   

xxxi

2-(Cyclohexylamino)ethanesulfonate

[CHES]

   

xxxii

2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethanesulfonate

[HEPES]

   

xxxiii

2-[(2-Hydroxy-1,1-[bis(hydroxy methyl)-ethyl)amino]ethanesulfonate

[TES]

   

xxxiv

2-Hydroxy-3-morpholinopropanesulfonate

[MOPSO]

   

xxxv

2-(Bis(2-hydroxyethyl)amino)ethanesulfonate

[BES]

   

xxxvi

N-[Tris(hydroxymethyl)methyl]-3-amino-2-hydroxypropanesulfonate

[TAPSO]

   

xxxvii

3-(Cyclohexylamino)-2-hydroxypropanesulfonate

[CAPSO]

Cholinium-Based ILs Versus Nitrogen-Based Cyclic ILs

The first reports on the field of IL aquatic toxicology including cholinium-based ILs date back to the first decade of the 2000s. These works have provided systematic insights on the factors responsible for ILs’ toxicity on aquatic compartments along the trophic web, e.g., A. fischeri, R. subcapitata, D. magna, and D. rerio [14, 15].

Large batteries of structurally different ILs were investigated: (i) [CnC1im]+, [CnC1pyr]+, 1-alkylpyridinium [Cnpyr]+, [CnC1pyrr]+, [CnC1mor]+, trialkylsulfonium [CnCnCnS]+, [Nwxyz]+, [Pwxyz]+, and [N111(2OH)]+, cations, bearing distinct alkyl side-chain lengths and functionalization groups; (ii) Cl, Br, [NTf2], [PF6], dicyanamide [N(CN)2], diethylphosphate [C2C2PO4], and methylsulphate [C1SO4] anions. In these two studies [14, 15], halogenated compounds incorporating the cholinium cation, namely, [N111(2OH)]Cl, [N111(2OH)][NTf2], and [N111(2OH)][PF6], were studied. Cholinium-based ILs were generally less toxic than the aromatic-based and the surfactant-like ammonium-based ILs [14, 15], matching the heuristic rules compiled above for the role of the cation head group and alkyl side chain upon aquatic toxicity. Organisms of different trophic levels displayed distinct sensitivity upon exposure to [N111(2OH)][PF6], i.e., the lower the position at the trophic hierarchy, the higher the toxic action (R. subcapitata > D. magnaD. rerio) [15].

In the set of studies published on the use of cholinium-based ILs are two works on the embryonic development of aquatic species [16, 17]. The main results suggested the negligible impact of [N111(2OH)]Cl on the embryogenic development of D. rerio in opposition to [C3C1pyrr][CF3SO3] (a fluorinated IL containing the trifluoromethanesulfonate anion, [CF3SO3]) and [N1111][C1CO2] [16]. Moreover, and along with [N111(2OH)][C1CO2], [N111(2OH)]Cl was the least hazardous IL to Artemia salina (A. salina) cysts, with [C4C1im][C1CO2], [C4C1im][NO3], and [N0001][NO3] reported as having an intermediate toxicity and [N111(2OH)][H2PO4] – a cholinium-based IL – consisting on the most toxic [17].

Summing up, the cholinium cation seems to represent a less toxic option for the synthesis of ILs than the widely used aromatic-based ones. Nevertheless, the scenario previously overviewed highlights the importance of avoiding overgeneralizations regarding the “nontoxic” nature of cholinium-based ILs, since it is highly contingent on the organism and anion structure.

Structure-Ecotoxicity Relationships Within Cholinium-Based ILs

Several efforts have been performed to disclose the structure-ecotoxicity relationships within cholinium-based ILs. Impacts imposed by the anion moiety [18, 19, 20] and structural modification in the cholinium cation [18, 19, 20, 21] over aquatic compartments were assessed.

Ten distinct anions were addressed concerning their toxicity over a complete battery of organisms along the aquatic trophic web (viz., A. fischeri, R. subcapitata, L. minor, and D. magna) [18, 19]. Table 3 overviews the anion role on the toxicity of cholinium-based ILs, indicating a great impact upon toxicity and a lack of toxicity output patterns among distinct biological models. The toxic action mechanisms of cholinium-based ILs are somehow intricate and deviate from the patterns widely accepted for other ILs by the aquatic toxicology community. The “side-chain effect” was observed with [CnCO2] anions only for D. magna (Table 3, entries viii, xii, and xx). The oxygenation role via the addition of one hydroxyl in organic acid-derived anions ([C1CO2] versus [HCO3]) has either null (L. minor) or positive (remaining test battery) effect on toxicity (Table 3, entries i–iv versus ix–xii), whereas further hydroxylation ([C1CO2] versus [Bit] and [DHCit]) increases the toxic action (Table 3, entries ix–xii versus xxix–xxxii and xxxiii–xxxvi). The anions bearing aromatic rings ([C1CO2] versus [Sal]) have no constant impacts over distinct organisms (Table 3, entries ix–xii versus xxv–xxviii) [18, 19]. Additionally, branching of alkanoate anions was shown to be beneficial on the toxicity toward A. fischeri [straight, [C9CO2], versus branched, [Cneo9CO2], anions, Table 3 entries xxxvii versus xxxviii] [28].
Table 3

Representative toxicity data for the anion role in cholinium-based ILs over different aquatic organisms

Entry

IL anion

Test organism

EC50 (mg.L−1)

Categorizationa

References

Cation: [N111(2OH)]+

i

[HCO3]

A. fischeri

>20,000

Practically harmless

[18]

ii

 

R. subcapitata

232.4

Practically harmless

[19]

iii

 

L. minor

483.6

Practically harmless

[19]

iv

 

D. magna

840.3

Practically harmless

[19]

v

[C3CO2]

A. fischeri

884.1

Practically harmless

[18]

vi

 

R. subcapitata

87.6

Acute 3

[19]

vii

 

L. minor

150.1

Practically harmless

[19]

viii

 

D. magna

637.3

Practically harmless

[19]

ix

[C1CO2]

A. fischeri

673.2

Practically harmless

[18]

x

 

R. subcapitata

124.1

Practically harmless

[19]

xi

 

L. minor

680.9

Practically harmless

[19]

xii

 

D. magna

694.6

Practically harmless

[19]

xiii

[H2PO4]

A. fischeri

572.7

Practically harmless

[18]

xiv

 

R. subcapitata

131.0

Practically harmless

[19]

xv

 

L. minor

1097

Practically harmless

[19]

xvi

 

D. magna

675.7

Practically harmless

[19]

xvii

[C2CO2]

A. fischeri

487.9

Practically harmless

[18]

xviii

 

R. subcapitata

50.17

Acute 3

[19]

xix

 

L. minor

149.1

Practically harmless

[19]

xx

 

D. magna

673.2

Practically harmless

[19]

xxi

Cl

A. fischeri

469.3

Practically harmless

[18]

xxii

 

R. subcapitata

72.51

Acute 3

[19]

xxiii

 

L. minor

234.2

Practically harmless

[19]

xxiv

 

D. magna

695.4

Practically harmless

[19]

xxv

[Sal]

A. fischeri

236.1

Practically harmless

[18]

xxvi

 

R. subcapitata

302.0

Practically harmless

[19]

xxvii

 

L. minor

110.1

Practically harmless

[19]

xxviii

 

D. magna

1086

Practically harmless

[19]

xxix

[Bit]

A. fischeri

37.90

Acute 3

[18]

xxx

 

R. subcapitata

27.26

Acute 3

[19]

xxxi

 

L. minor

1063

Practically harmless

[19]

xxxii

 

D. magna

410.5

Practically harmless

[19]

xxxiii

[DHCit]

A. fischeri

37.23

Acute 3

[18]

xxxiv

 

R. subcapitata

87.16

Acute 3

[19]

xxxv

 

L. minor

1863

Practically harmless

[19]

xxxvi

 

D. magna

445.0

Practically harmless

[19]

xxxvii

[C9CO2]

A. fischeri

28

Acute 3

[28]

xxxviii

[Cneo9CO2]

A. fischeri

145

Practically harmless

[28]

xxxix

[Ci17CO2]

A. fischeri

29

Acute 3

[28]

Cation: [N00(2OH)(2OH)]+

xl

[C0CO2]

A. fischeri

800

Practically harmless

[20]

xli

 

R. subcapitata

976

Practically harmless

[20]

xlii

 

L. minor

525

Practically harmless

[20]

xliii

[C1CO2]

A. fischeri

1750

Practically harmless

[20]

xliv

 

R. subcapitata

870

Practically harmless

[20]

xlv

 

L. minor

631

Practically harmless

[20]

xlvi

[C2CO2]

A. fischeri

650

Practically harmless

[20]

xlvii

 

R. subcapitata

2569

Practically harmless

[20]

xlviii

 

L. minor

209

Practically harmless

[20]

xlix

[C3CO2]

A. fischeri

800

Practically harmless

[20]

l

 

R. subcapitata

294

Practically harmless

[20]

li

 

L. minor

33

Acute 3

[20]

lii

[Ci3CO2]

A. fischeri

850

Practically harmless

[20]

liii

 

R. subcapitata

1275

Practically harmless

[20]

liv

 

L. minor

79

Acute 3

[20]

lv

[C4CO2]

A. fischeri

350

Practically harmless

[20]

lvi

 

R. subcapitata

574

Practically harmless

[20]

lvii

 

L. minor

155

Practically harmless

[20]

a“Acute 1” EC50 ≤ 1 mg.L−1 | “Acute 2” EC50 >1 mg.L−1 but ≤10 mg.L−1 | “Acute 3” EC50 >10 mg.L−1 but ≤100 mg.L−1 | [11] “Practically harmless” EC50 >100 mg.L−1

Table 4 provides representative toxicological data for cholinium-based ILs designed with structural modifications at the cation. Around twenty five structures were screened over A. fischeri in the works by Ventura and collaborators [18, 21]. The data suggested that the increase in the alkyl side or linkage chains induced toxicity, a result in good agreement with the well-documented “side-chain effect” (Table 4, entries ix–xv and xvi–xix). Moreover, by incorporating hydroxyethyl groups in the cholinium derivative structures, the authors observed an increased toxic action (Table 4, entries xx–xxii), on a clear opposition to the oxygenation role in common ILs. The insertion of carbon-carbon double bonds was also studied and proved to be able to decrease or maintain the toxicity, while triple bonds imposed higher toxicity levels (Table 4 entries xxiii–xv and xvi–xvii). The incorporation of a benzyl group in the cholinium cation rendered no constant impacts over distinct organisms, viz. A. vibrio, L. minor, R. subcapitata, and D. magna [18, 19] (Table 4, entries i–iv versus v–viii), being the same impact found when disclosing the role of aromatic anions (Table 3, entries ix–xii versus xxv–xxviii). Protic cations, where the methyl group linked to the central nitrogen was substituted by a hydrogen atom, were found to be more toxic than its aprotic counterparts (Table 4, entries xxviii–xxix). Finally, dicationic cholinium-based ILs were also investigated, these structures being defined by the presence of two cations connected by an alkyl chain and conjugated with two anions. In this work [21], the dicationic cholinium-based ILs are described as less toxic than the parent monocationic compounds (Table 4, entries xiii–xix).
Table 4

Representative toxicity data for the cation role in cholinium-based ILs and over different aquatic organisms

Entry

IL cation

Test organism

EC50 (mg.L−1)

Categorizationa

References

Anion: Cl

i

[N111(2OH)]+

A. fischeri

469.3

Practically harmless

[18]

ii

 

R. subcapitata

72.51

Acute 3

[19]

iii

 

L. minor

234.2

Practically harmless

[19]

iv

 

D. magna

695.4

Practically harmless

[19]

v

[N11(C7H7)(2OH)]+

A. fischeri

1498

Practically harmless

[18]

vi

 

R. subcapitata

196.2

Practically harmless

[19]

vii

 

L. minor

11.86

Acute 3

[19]

viii

 

D. magna

217.5

Practically harmless

[19]

Anion: Br

ix

[N112(2OH)]+

A. fischeri

25619.07

Practically harmless

[21]

x

[N113(2OH)]+

 

33972.39

Practically harmless

[21]

xi

[N114(2OH)]+

 

13442.88

Practically harmless

[21]

xii

[N115(2OH)]+

 

3016.96

Practically harmless

[21]

xiii

[N116(2OH)]+

 

746.30

Practically harmless

[21]

xiv

[N118(2OH)]+

 

162.96

Practically harmless

[21]

xv

[N1112(2OH)]+

 

0.81

Acute 1

[21]

Anion: 2(Br)

xvi

[N1(2OH)(2OH)-C6-[N1(2OH)(2OH)]2+

A. fischeri

6117.15

Practically harmless

[21]

xvii

[N1(2OH)(2OH)-C8-[N1(2OH)(2OH)]2+

 

5579.82

Practically harmless

[21]

xviii

[N1(2OH)(2OH)-C10-[N1(2OH)(2OH)]2+

 

388.95

Practically harmless

[21]

xix

[N1(2OH)(2OH)-C12-[N1(2OH)(2OH)]2+

 

97.89

Acute 3

[21]

Anion: Br

xx

[N116(2OH)]+

A. fischeri

746.30

Practically harmless

[21]

xxi

[N16(2OH)(2OH)]+

 

276.96

Practically harmless

[21]

xxii

[N6(2OH)(2OH)(2OH)]+

 

19.74

Acute 3

[21]

xxiii

[N113(2OH)]+

 

33972.39

Practically harmless

[21]

xxiv

[N11(3enyl)(2OH)]+

 

20798.81

Practically harmless

[21]

xxv

[N11(3ynyl)(2OH)]+

 

235.92

Practically harmless

[21]

xxvi

[N13(2OH)(2OH)]+

 

1601.29

Practically harmless

[21]

xxvii

[N1(3enyl)(2OH)(2OH)]+

 

2745.90

Practically harmless

[21]

xxviii

[N13(2OH)(2OH)]+

 

1601.29

Practically harmless

[21]

xxix

[N03(2OH)(2OH)]+

 

370.07

Practically harmless

[21]

Anion: [C3CO2]

xxx

[N000(2OH)] +

A. fischeri

2239

Practically harmless

[20]

xxxi

 

R. subcapitata

104

Practically harmless

[20]

xxxii

 

L. minor

59

Acute 3

[20]

xxxiii

[N00(2OH)(2OH)] +

A. fischeri

800

Practically harmless

[20]

xxxiv

 

R. subcapitata

294

Practically harmless

[20]

xxxv

 

L. minor

33

Acute 3

[20]

xxxvi

[N0(2OH)(2OH)(2OH)] +

A. fischeri

501

Practically harmless

[20]

xxxvii

 

R. subcapitata

1287

Practically harmless

[20]

xxxviii

 

L. minor

178

Practically harmless

[20]

a“Acute 1” EC50 ≤1 mg.L−1 | “Acute 2” EC50 >1 mg.L−1 but ≤10 mg.L−1 | “Acute 3” EC50 >10 mg.L−1 but ≤100 mg.L−1 | [11] “Practically harmless” EC50 >100 mg.L−1

Stolte and collaborators [20] found no well-defined trends for cholinium protic derivatives (e.g., [N000(2OH)][CnCO2], [N00(2OH)(2OH)][CnCO2], and [N0(2OH)(2OH)(2OH)][CnCO2], with 0 ≤ n ≤ 4) regarding the number of hydroxyethyl groups of the cation (Table 4, entries xxx–xxxviii) and the alkyl side chain of the [CnCO2] anion (Table 3, entries xl–lvii) among distinct aquatic compartments. For instance, the higher the number of hydroxyethyl groups, the higher the toxicity for A. fischeri (Table 4, entries xxx versus xxxiii versus xxxvi), what agrees with the findings by e Silva et al. using the same microorganism [21]. Still, a reverse trend is observed over R. subcapitata, likely due to differences at the level of the cell wall, as assumed in other studies [19]. L. minor was the most sensitive aquatic organism found [20], in opposition to the observations by Santos et al. [19] for aprotic, more common cholinium-based compounds where algae displayed the highest sensitivity (Table 4).

From the results found so far, the data suggested that common aprotic ILs (e.g., [CnC1im]Cl and [C4pyr]Cl) are more toxic to A. fischeri, L. minor, and R. subcapitata than these protic cholinium derivatives [20]. The presence of both shorter alkyl side chains and hydrophilic functional groups (e.g., hydroxyethyl and hydrogen atoms) contributes for such pattern. With regard to aprotic cholinium-based ILs, Ventura et al. [18] have recognized, however, that some of the general patterns considered in literature are distinct. The higher toxicity of the cholinium structure when compared with other IL cations (e.g., [N1124]+, [C2C1im]+, all sharing the Cl anion) implies that for some cholinium ILs, the mechanism of toxic action may be different than that accepted for other ILs. Moreover, as revealed by Rantamäki et al., the higher EC50 values of guanidinium over cholinium-based cations may lead to a stepping stone in the development of less toxic ILs [28]. Additionally, cholinium-based ILs may present a higher toxicity than conventional organic solvents (e.g., ethyl acetate and dichloromethane), often influenced by the anion structure [18], what challenges the inherently safer nature of this class of compounds.

Finally, differential scanning calorimetry (DSC) studies to correlate the EC50 values of cholinium-based ILs with the rupture point of biomimetic lipid bilayers were done [28]. With ILs bearing long-chain alkanoate anions, the liposomes were affected by the ILs presence correlating the EC50 values and the IL critical micelle concentration [28]. Works of such kind bring major progresses on understanding IL-biological membrane interactions.

Strategies to Develop Less Toxic Cholinium-Based ILs

Taking into account the heuristic rules defined in the last years for different organisms and trophic levels, the search for less toxic cholinium-based ILs continued. Cholinium structures incorporating biocompatible anions, such as amino acids (abbreviated as [N111(2OH)][AA]), have evolved aiming at the ILs’ synthesis under sustainable and environmentally friendly principles for ILs’ design [12].

The aquatic toxicity of [N111(2OH)][AA] was addressed by covering three aquatic organisms (R. subcapitata, A. salina, and D. rerio) of different trophic levels (viz., green algae, brine shrimp, and zebra fish) and a plethora of amino acids, as represented in Table 5 [22, 23]. Consistency with the literature previously discussed was found related with the nontoxic nature of [N111(2OH)][AA] compared to their imidazolium congeners [22] and the “side-chain effect” of the anion (e.g., [Gly] versus [Ala] versus [Leu] – Table 5, entries i–iii versus iv–vi versus vii–ix) [22, 23]. Nevertheless, the introduction of nitrogen heterocycles and benzyl groups at the amino acid anion allowed decreasing the toxicity toward brine shrimp, zebra fish, and green algae (e.g., [Ala] versus [His], [Pro], [Phe], and [Trp] in Table 5) – a result of the lower IL lipophilicity when compared to the aliphatic correspondent [23]. Such a phenomenon is opposite to what has been observed for the toxicity of common ILs, but in agreement with some of the patterns disclosed for cholinium-based ILs [18, 19].
Table 5

Representative toxicity data for [N111(2OH)][AA] over different aquatic organisms

Entry

[AA] anion

Test organism

LC50/EC50 (mg.L−1)

Categorizationa

References

i

[Gly]

A. salina

15952.10

Practically harmless

[23]

ii

 

D. rerio

226.33

Practically harmless

[23]

iii

 

R. subcapitata

5766.63

Practically harmless

[23]

iv

[Ala]

A. salina

9968.91

Practically harmless

[23]

v

 

D. rerio

179.57

Practically harmless

[23]

vi

 

R. subcapitata

2474.40

Practically harmless

[23]

vii

[Leu]

A. salina

9156.29

Practically harmless

[23]

viii

 

D. rerio

160.86

Practically harmless

[23]

ix

 

R. subcapitata

1011.56

Practically harmless

[23]

x

[Met]

A. salina

6515.87

Practically harmless

[23]

xi

 

D. rerio

155.16

Practically harmless

[23]

xii

 

R. subcapitata

1031.31

Practically harmless

[23]

xiii

[His]

A. salina

19213.91

Practically harmless

[23]

xiv

 

D. rerio

274.46

Practically harmless

[23]

xv

 

R. subcapitata

9997.21

Practically harmless

[23]

xvi

[Pro]

A. salina

11186.72

Practically harmless

[23]

xvii

 

D. rerio

184.76

Practically harmless

[23]

xviii

 

R. subcapitata

4343.72

Practically harmless

[23]

xix

[Phe]

A. salina

15720.64

Practically harmless

[23]

xx

 

D. rerio

203.52

Practically harmless

[23]

xxi

 

R. subcapitata

3952.16

Practically harmless

[23]

xxii

[Trp]

A. salina

15383.49

Practically harmless

[23]

xxiii

 

D. rerio

194.27

Practically harmless

[23]

xxiv

 

R. subcapitata

3723.89

Practically harmless

[23]

a“Acute 1” LC50/EC50 ≤1 mg.L−1 | “Acute 2” LC50/EC50 >1 mg.L−1 but ≤10 mg.L−1 | “Acute 3” LC50/EC50 >10 mg.L−1 but ≤100 mg.L−1 | [11] “Practically harmless” LC50/EC50 >100 mg.L−1

Balancing the “Innocuous Nature” and “High Performance” with Cholinium ILs

Above, insights on the ecotoxicity of cholinium-based ILs were collected and discussed. Although ILs were previously seen as “greener” substitutes for nitrogen-based cyclic ILs (e.g., [CnC1im]-based) [14, 15, 16, 17], studies on structure-ecotoxicity relationships called the attention for the nefarious effects associated to both cation and anion structures [18, 19, 20, 21, 22, 23]. Still, the studies here discussed provide useful information for the design of less toxic cholinium-based ILs but fail in integrating their ecotoxicological profile and respective applications [14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. Examples of cases combining an evaluation of ecotoxicity with the application in the pharmaceutical (e.g., formulation of drugs [24]), chemical (e.g., formulation of detergents [25]), and biotechnological (e.g., production and extraction of biomolecules [26, 27]) fields will be overviewed, with the data presented in Table 6.
Table 6

Representative toxicity data for cholinium-based ILs used for distinct applications

Entry

Anion/precursor

Test organism

IL EC50 (mg.L−1)

IL categorizationa

Precursor EC50 (mg.L−1)

Precursor categorizationa

References

IL-APIs

i

[Van]/vanillic acid

A. fischeri

1000.6

Practically harmless

27.5

Acute 3

[24]

ii

[Caf]/caffeic acid

 

856.3

Practically harmless

n.d.b

[24]

iii

[Syr]/syringic acid

 

568.5

Practically harmless

32.5

Acute 3

[24]

iv

[Gal]/gallic acid

 

1725.4

Practically harmless

32.1

Acute 3

[24]

v

[Sal]/salicylic acid

 

221.1–236.1

Practically harmless

15.2

Acute 3

[18, 24]

vi

[Ell]2−/ellagic acid

 

n.d.b

n.d.b

[24]

SA-ILs

Vii

[DBS]/n.a.c

Scenedesmus sp.

Maximum number of live cells unaffected

n.a.c

[25]

GB-ILs

viii

[TES]/TES

A. vibrio

>60,000

Practically harmless

661.17

Practically harmless

[26, 29]

ix

[HEPES]/HEPES

 

19,584

Practically harmless

8684.08

Practically harmless

[26, 29]

x

[CAPSO]/CAPSO

 

19504.46

Practically harmless

3068.88

Practically harmless

[27]

xi

[MES]/MES

 

9789

Practically harmless

214.74

Practically harmless

[26, 29]

xii

[BES]/BES

 

7327.89

Practically harmless

2225.00

Practically harmless

[27]

xiii

[MOPSO]/MOPSO

 

6132.40

Practically harmless

1245.47

Practically harmless

[27]

xiv

[Tricine]/Tricine

 

4588

Practically harmless

6040.57

Practically harmless

[26, 29]

xv

[TAPSO]/TAPSO

 

3439.25

Practically harmless

965.42

Practically harmless

[27]

xvi

[CHES]/CHES

 

208.65

Practically harmless

16497.82

Practically harmless

[26, 29]

a“Acute 1” EC50 ≤1 mg L−1 | “Acute 2” EC50 >1 mg.L−1 but ≤10 mg.L−1 | “Acute 3” EC50 >10 mg.L−1 but ≤100 mg.L−1 | [11] “Practically harmless” EC50 >100 mg.L−1

bNot determined due to solubility issues

cNot assessed

ILs bearing active pharmaceutical ingredients (IL-APIs) represent an auspicious strategy to overcome the polymorphism and bioavailability issues of common APIs; yet, the toxicity of some ILs is still limiting their real application. Within this framework [24], Sintra et al. synthesized antioxidant IL-APIs exclusively obtained from natural sources. By pairing the cholinium cation and phenolic acids as the anion moiety, the authors provided a complete physical, chemical, and biological characterization [24]. It was possible to deliver a new set of IL-API chemicals, displaying better bioactivity (antioxidant and anti-inflammatory) and bioavailability (water solubility) than the parent acidic compounds. Such achievements assemble comparable cytotoxic profiles and lower ecotoxicity, showcasing the promising applicability in dermatological formulations and oral drugs [24]. The aquatic toxicity studies using A. fischeri revealed that all are practically harmless to the environment (Table 6, entries i–vi) [11]. Regarding the structure-ecotoxic relationships, the increased number of methoxy groups in the aromatic rings of the anion (i.e., [Van] versus [Syr], Table 6 entry i versus iii) was found to induce higher toxic effects over A. fischeri [24]. These findings support the idea that oxygenation may limit the benign nature of cholinium-based ILs [18, 19, 20, 21], in opposition to what has been reported for [CnC1im]-based ILs.

Gehlot et al. [25] focused on surface-active ILs (SA-ILs) as candidates to overcome surface activity and water solubility issues of the conventional surfactants (e.g., sodium dodecylbenzenesulfonate, Na[DBS]). Envisioning their application in detergent formulations, the synthesis and full characterization of [N111(2OH)][DBS] was performed (e.g., surface activity, enzymatic activity, and ecotoxicity) [25]. These studies revealed enhanced surface-active properties and lower critical micelle concentration than Na[DBS]. At the same time, the SA-IL synthesized allowed the improvement of enzymatic activity while being revealed as nontoxic for the freshwater microalgae Scenedesmus sp. (microalgae growth was not affected as shown in Table 6, entry vii) [25].

The development of self-buffering and biocompatible ILs has led to remarkable progresses in biotechnological and biopharmaceutical applications. The studies reported are recurrently investigating purification processes by the implementation of aqueous biphasic systems (i.e., water-rich liquid-liquid extraction systems formed by aqueous solutions of two incompatible solutes, such as IL-salt, IL-polymer, IL-carbohydrate) [26, 27]. The literature available covers nine cholinium-based ILs bearing anions derived from Good’s buffers (further abbreviated as [N111(2OH)][GB]) and their applicability in the purification of antibodies from hen egg yolk [26] and lipase from fermentation broth [27]. Regardless of the [GB] anion structure, all [N111(2OH)][GB] are categorized as “practically harmless” (EC50 >100 mg.L−1, A. fischeri – Table 6, entries viii–xvi) and exhibit enhanced environmental features compared to other classes of ILs (e.g., [N4444]+ and [P4444]+) and their GBs congeners (except [CHES]and [Tricine] – cf. Table 6, entries viii–xvi) [26, 27, 29]. In line with the controversy with the oxygenation role in the toxicity of cholinium-based ILs [18, 19, 20, 21, 24], the structure-ecotoxicity relationships dictate that the taurine derivative lacking oxygenated substituent groups (e.g., [CHES] – Table 6, entry xvi) is by far the most toxic [N111(2OH)][GB] [26]. In opposition, within [GBs] oxygenated via the addition of hydroxyl groups, a proportional relationship between the number of oxygenated elements and toxicity is observed (e.g., [MOPSO], [TAPSO], and [CAPSO] – Table 6, entry x versus xiii versus xv) [27]. [N111(2OH)][GB]-based structures were shown to offer relevant advantages to the proposed applications, namely, wide buffering capacity, good stabilizing power for biomolecules, and no toxicity, while yielding enhanced extraction efficiency and selectivity data [26, 27].

Remarkably, all studies discussed above were able to find a good compromise between the structure-ecotoxicity-application relationships by applying cholinium-based ILs [24, 25, 26, 27]. The cautious design of cholinium-based ILs as APIs, additives, or solvents allowed either keeping or improving the performance while lowering the environmental impact of current applications. Still, such studies [24, 25, 26, 27] lack comprehensive ecotoxic evaluations, revealing the need for further investigation for other organisms of the aquatic trophic chain and other types of toxicity studies.

Conclusions

Considering the toxicity displayed by some ILs, particularly the most common nitrogen-based cyclic of aromatic nature, e.g., those based on [CnC1im]+ and [CnC1pyr]+, cholinium-based ILs emerge as less toxic and more sustainable chemicals. Such notion is firstly supported by aquatic toxicology studies including cholinium-based ILs as part of the ILs’ battery investigated, mainly using halogenated anions (e.g., [N111(2OH)]Cl, [N111(2OH)][NTf2], and [N111(2OH)][PF6]). Systematic studies devoted to structure-ecotoxicity relationships controlling the toxicity of cholinium-based ILs, where the role of both the anion and cation structures was evaluated, are reviewed. The well-documented “side-chain effect” was consistently observed by elongating the alkyl chains of the cation (e.g., [N11n(2OH)]+), while deviations were observed for the [CnCO2]-based anions. The effects noticed for both the inclusion of oxygenated and aromatic groups on the ecotoxicity were intricate and highly dependent on the cation/anion combinations and the organism under study. The introduction of naturally occurring amino acids as anions is a feasible route to create eco-friendly cholinium-based ILs, but there must be a careful choice of the amino acid used.

Based on the summarized results, it can be concluded that depending on the cationic and anionic parts combined, some cholinium-based ILs may exhibit higher toxicity than nitrogen-based cyclic of aromatic nature, namely, those based on [CnC1im]+, and some volatile organic solvents. The data available highlights a different mode of toxic action for this class of ILs and challenges its “benign” nature often claimed a priori by many researchers. Under this scenario, the overgeneralized idea that cholinium-based ILs are safe and environmentally innocuous chemicals should definitely be avoided. At least, aquatic toxicity data covering organisms along different levels of the trophic web and different types of toxicity tests other than acute toxicity (e.g., chronic, reproductive, developmental, and embryo toxicity) as well as cytotoxicity, terrestrial toxicity, and antimicrobial activity profiles should be investigated before considering cholinium-based ILs as nontoxic. However, given the variety and variability of ILs, this task of an empirical evaluation of the toxicity of all ILs is not feasible and thus mathematical models [e.g., quantitative structure-activity relationships (QSARs) and quantitative structure-property relationships (QSPRs)] must be developed and applied (e.g., [14, 30]).

The environmental impact of ILs, however, must not be only based on toxicity data. The whole life cycle of cholinium-based ILs should be carefully evaluated in a way that all steps, meaning, from their synthesis/production and application until their discharge, should be contemplated. It should be highlighted that simpler and cleaner synthetic routes have been reported, based on the use of naturally occurring precursors [22, 24]. As recently highlighted by Jessop [31], the lack of life cycle assessments of ILs-mediated applications is precluding the evolution of the field, and, therefore, these are urgent. The challenge now is to ally both “designer” and “green” concepts to develop “high performance” and safer processes and products.

Notes

Acknowledgments

This work was developed within the scope of the project CICECO – Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The authors also acknowledge the support by the Portuguese Foundation for Science and Technology (FCT) through the project PTDC/ATP-EAM/5331/2014. F. A. e Silva acknowledges the financial support given by FCT within the PhD scholarship SFRH/BD/94901/2013. S. P. M. Ventura acknowledges FCT/MEC for a contract under Investigador FCT 2015 contract number IF/00402/2015.

References

  1. 1.
    Schubert TJS (2017) Current and future ionic liquid markets. In: Ionic liquids: current state and future directions, vol 1250. American Chemical Society, Washington, DC pp 35–65Google Scholar
  2. 2.
    Plechkova NV, Seddon KR (2008) Applications of ionic liquids in the chemical industry. Chem Soc Rev 37(1):123–150CrossRefGoogle Scholar
  3. 3.
    Claus J, Sommer FO, Kragl U (2018) Ionic liquids in biotechnology and beyond. Solid State Ionics 314:119–128CrossRefGoogle Scholar
  4. 4.
    Chiappe C, Pieraccini D (2005) Ionic liquids: solvent properties and organic reactivity. J Phys Org Chem 18(4):275–297CrossRefGoogle Scholar
  5. 5.
    Welton T (2018) Ionic liquids: a brief history. Biophys Rev 10(3):691–706CrossRefGoogle Scholar
  6. 6.
    Kunz W, Häckl K (2016) The hype with ionic liquids as solvents. Chem Phys Lett 661:6–12CrossRefGoogle Scholar
  7. 7.
    Egorova KS, Ananikov VP (2014) Toxicity of ionic liquids: eco(cyto)activity as complicated, but unavoidable parameter for task-specific optimization. ChemSusChem 7(2):336–360CrossRefGoogle Scholar
  8. 8.
    Richardson SD, Ternes TA (2018) Water analysis: emerging contaminants and current issues. Anal Chem 90(1):398–428CrossRefGoogle Scholar
  9. 9.
    Petkovic M, Seddon KR, Rebelo LPN, Silva Pereira C (2011) Ionic liquids: a pathway to environmental acceptability. Chem Soc Rev 40(3):1383–1403CrossRefGoogle Scholar
  10. 10.
    Matzke M, Arning J, Ranke J, Jastorff B, Stolte S (2009) Design of inherently safer ionic liquids: toxicology and biodegradation. In: Anastas PT (ed) Handbook of green chemistryGoogle Scholar
  11. 11.
    Part 4 – Environmental Hazards. United Nations, New York and Geneva https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs_rev01/English/04e_part4.pdf. Accessed 16 Oct 2018
  12. 12.
    Gontrani L (2018) Choline-amino acid ionic liquids: past and recent achievements about the structure and properties of these really “green” chemicals. Biophys Rev 10(3):873–880CrossRefGoogle Scholar
  13. 13.
    Zeisel SH, da Costa K-A (2009) Choline: an essential nutrient for public health. Nutr Rev 67(11):615–623CrossRefGoogle Scholar
  14. 14.
    Couling DJ, Bernot RJ, Docherty KM, Dixon JK, Maginn EJ (2006) Assessing the factors responsible for ionic liquid toxicity to aquatic organisms via quantitative structure–property relationship modeling. Green Chem 8(1):82–90CrossRefGoogle Scholar
  15. 15.
    Pretti C, Chiappe C, Baldetti I, Brunini S, Monni G, Intorre L (2009) Acute toxicity of ionic liquids for three freshwater organisms: Pseudokirchneriella subcapitata, Daphnia magna and Danio rerio. Ecotoxicol Environ Saf 72(4):1170–1176CrossRefGoogle Scholar
  16. 16.
    Younes N, Salem R, Al-Asmakh M, Altamash T, Pintus G, Khraisheh M, Nasrallah GK (2018) Toxicity evaluation of selected ionic liquid compounds on embryonic development of Zebrafish. Ecotoxicol Environ Saf 161:17–24CrossRefGoogle Scholar
  17. 17.
    Sakamoto M, Ohama Y, Aoki S, Fukushi K, Mori T, Yoshimura Y, Shimizu A (2018) Effect of ionic liquids on the hatching of Artemia salina cysts. Aust J Chem 71(7):492–496Google Scholar
  18. 18.
    Ventura SPM, e Silva FA, Gonçalves AMM, Pereira JL, Gonçalves F, Coutinho JAP (2014) Ecotoxicity analysis of cholinium-based ionic liquids to Vibrio fischeri marine bacteria. Ecotoxicol Environ Saf 102:48–54CrossRefGoogle Scholar
  19. 19.
    Santos JI, Gonçalves AMM, Pereira JL, Figueiredo BFHT, e Silva FA, Coutinho JAP, Ventura SPM, Gonçalves F (2015) Environmental safety of cholinium-based ionic liquids: assessing structure–ecotoxicity relationships. Green Chem 17(9):4657–4668CrossRefGoogle Scholar
  20. 20.
    Peric B, Sierra J, Martí E, Cruañas R, Garau MA, Arning J, Bottin-Weber U, Stolte S (2013) (Eco)toxicity and biodegradability of selected protic and aprotic ionic liquids. J Hazard Mater 261:99–105CrossRefGoogle Scholar
  21. 21.
    e Silva FA, Siopa F, Figueiredo BFHT, Gonçalves AMM, Pereira JL, Gonçalves F, Coutinho JAP, Afonso CAM, Ventura SPM (2014) Sustainable design for environment-friendly mono and dicationic cholinium-based ionic liquids. Ecotoxicol Environ Saf 108:302–310CrossRefGoogle Scholar
  22. 22.
    Gouveia W, Jorge TF, Martins S, Meireles M, Carolino M, Cruz C, Almeida TV, Araújo MEM (2014) Toxicity of ionic liquids prepared from biomaterials. Chemosphere 104:51–56CrossRefGoogle Scholar
  23. 23.
    Zhang S, Ma L, Wen P, Ye X, Dong R, Sun W, Fan M, Yang D, Zhou F, Liu W (2018) The ecotoxicity and tribological properties of choline amino acid ionic liquid lubricants. Tribol Int 121:435–441CrossRefGoogle Scholar
  24. 24.
    Sintra TE, Luís A, Rocha SN, Lobo Ferreira AIMC, Gonçalves F, Santos LMNBF, Neves BM, Freire MG, Ventura SPM, Coutinho JAP (2015) Enhancing the antioxidant characteristics of phenolic acids by their conversion into cholinium salts. ACS Sustain Chem Eng 3(10):2558–2565CrossRefGoogle Scholar
  25. 25.
    Gehlot PS, Kulshrestha A, Bharmoria P, Damarla K, Chokshi K, Kumar A (2017) Surface-active ionic liquid cholinium dodecylbenzenesulfonate: self-assembling behavior and interaction with cellulase. ACS Omega 2(10):7451–7460CrossRefGoogle Scholar
  26. 26.
    Taha M, Almeida MR, e Silva FA, Domingues P, Ventura SPM, Coutinho JAP, Freire MG (2015) Novel biocompatible and self-buffering ionic liquids for biopharmaceutical applications. Chem Eur J 21(12):4781–4788CrossRefGoogle Scholar
  27. 27.
    Lee SY, Vicente FA, e Silva FA, Sintra TE, Taha M, Khoiroh I, Coutinho JAP, Show PL, Ventura SPM (2015) Evaluating self-buffering ionic liquids for biotechnological applications. ACS Sustain Chem Eng 3(12):3420–3428CrossRefGoogle Scholar
  28. 28.
    Rantamäki AH, Ruokonen S-K, Sklavounos E, Kyllönen L, King AWT, Wiedmer SK (2017) Impact of surface-active guanidinium-, tetramethylguanidinium-, and cholinium-based ionic liquids on vibrio fischeri cells and dipalmitoylphosphatidylcholine liposomes. Sci Rep 7:46673CrossRefGoogle Scholar
  29. 29.
    Taha M, e Silva FA, Quental MV, Ventura SPM, Freire MG, Coutinho JAP (2014) Good’s buffers as a basis for developing self-buffering and biocompatible ionic liquids for biological research. Green Chem 16(6):3149–3159CrossRefGoogle Scholar
  30. 30.
    Roy K, Das RN, Popelier PLA (2014) Quantitative structure–activity relationship for toxicity of ionic liquids to Daphnia magna: aromaticity vs. lipophilicity. Chemosphere 112:120–127CrossRefGoogle Scholar
  31. 31.
    Jessop PG (2018) Fundamental properties and practical applications of ionic liquids: concluding remarks. Faraday Discuss 206:587–601CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Francisca A. e Silva
    • 1
  • João A. P. Coutinho
    • 1
  • Sónia P. M. Ventura
    • 1
    Email author
  1. 1.Chemistry Department, CICECOUniversity of AveiroAveiroPortugal

Section editors and affiliations

  • Chunxi Li
    • 1
  • Stefan Stolte
  1. 1.Chemical EngineeringBeijing University of Chemical TechnologyBeijingChina