Ecotoxicological Evaluation of Magnetic Ionic Liquids

Supporting Information

Ecotoxicological evaluation of magnetic ionic liquids

Tânia E. Sintra1, Maryam Nasirpour1, Filipa Siopa2, Andreia A. Rosatella2, Fernando Gonçalves3, João A. P. Coutinho1, Carlos A. M. Afonso2 and Sónia P. M. Ventura1*

1CICECO - Aveiro Institute of Materials & Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal

2Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal

3Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal

*Corresponding author:

Tel: +351-234-370200; Fax: +351-234-370084; E-mail address: [email protected] Materials

All solvents were distilled prior use. All chemicals were purchased from Aldrich. The 1H

13 and C-NMR spectra were obtained in D2O on a Bruker ARX 400 spectrometer, at 400 and 100.62 MHz, respectively. The chemical shifts are expressed in parts per million (ppm) relative to tetramethylsilane (TMS). The coupling constants (J) are reported in Hertz (Hz). ICP-AES (Inductively Coupled Plasma-Atomic Emission Spectrometer) analyse was performed by Laboratório de Análises at REQUIMTE, Portugal. Elemental analysis (Flash2000 CHNS-O analyzer (ThermoScientific,UK)), and ESI-MS analysis (Micromass Quattro Micro triplequadrupole (Waters, Ireland) with an electrospray (ESI) ion source) were performed at Mass Spectrometry Service in Faculdade de Farmácia (Universidade de Lisboa, Portugal).

General method for the synthesis of MILs

General method for cholinium chloride derivative based ILs

The MILs listed in Table S1 were prepared using reported procedures with some modifications.

Table S1. MILs prepared using reported procedures.1,2

Chemical Structure Acronym Name Ref. (2-hydroxyethyl) 1 + - N FeCl4 HO [N1,1,1,2(OH)][FeCl4] trimethylammonium iron tetrachloride (2-hydroxyethyl) 1 N+ MnCl 2- HO 4 2 [N1,1,1,2(OH)]2[MnCl4] trimethylammonium manganese tetrachloride (2-hydroxyethyl) 1

[N1,1,1,2(OH)]2[CoCl4] trimethylammonium cobalt tetrachloride 1 (2-hydroxyethyl) N+ GdCl 3- HO 6 [N ] [GdCl ] trimethylammonium gadolinium 3 1,1,1,2(OH) 3 6 hexachloride (2-hydroxyethyl) ethyl 1

[N1,1,2,2(OH)][FeCl4] dimethylammonium iron tetrachloride 2 HO Hexyl di(2-hydroxyethyl) - N+ FeCl4 [N ][FeCl ] methylammonium iron HO 1,6,2(OH),2(OH) 4 tetrachloride 2 HO 2- Hexyl di(2-hydroxyethyl) N+ MnCl4 HO [N1,6,2(OH),2(OH)]2[MnCl4] methylammonium manganese 2 tetrachloride

2 HO 2- Hexyl di(2-hydroxyethyl) N+ CoCl4 HO [N1,6,2(OH),2(OH)]2[CoCl4] methylammonium cobalt 2 tetrachloride 2 HO 3- Hexyl di(2-hydroxyethyl) N+ GdCl6 HO [N1,6,2(OH),2(OH)]3[GdCl6] methylammonium gadolinium 3 hexachloride Hexyl tri(2-hydroxyethyl) 2 [N ][FeCl ] 6,2(OH),2(OH),2(OH) 4 ammonium iron tetrachloride 2 OH HO 2- Hexyl tri(2-hydroxyethyl) N+ MnCl4 HO [N6,2(OH),2(OH),2(OH)]2[MnCl4] ammonium manganese 2 tetrachloride

2 OH HO 2- N+ CoCl4 Hexyl tri(2-hydroxyethyl) HO [N6,2(OH),2(OH),2(OH)]2[CoCl4] 2 ammonium cobalt tetrachloride

2 OH HO 3- Hexyl tri(2-hydroxyethyl) N+ GdCl6 HO [N6,2(OH),2(OH),2(OH)]3[GdCl6] ammonium gadolinium 3 hexachloride 1 - Hexyl (2-hydroxyethyl) N+ FeCl4 HO [N1,1,6,2(OH)][FeCl4] dimethylammonium iron tetrachloride (2-hydroxyethyl) dimethyl 1 [N ][FeCl ] 1,1,8,2(OH) 4 octylammonium iron tetrachloride 1 + - Dodecyl (2-hydroxyethyl) N FeCl4 HO 5 [N1,1,12,2(OH)][FeCl4] dimethylammonium iron tetrachloride

Synthetic procedures

Butyl di(2-hydroxyethyl) methylammonium chloride, [N1,4,2(OH),2(OH)]Cl In a round bottom flask at room temperature was added 1-chlorobutane (408 mmol, 4 mole eq.), methyl diethanolamine (102 mmol) and sodium iodide (30.6 mmol, 0.3 moles eq.). The reaction mixture was heated at 80 ºC during 7 days. The excess of 1-chlorobutane was removed by evaporation under vacuum and sodium salt was removed by adding dichloromethane to the ionic liquid, followed by filtration and evaporation. The compound was dried under vacuum and recovered as a yellow liquid in 80% yield. 1H NMR (400

MHz, D2O) δ 3.99 (s, 4H), 3.56 – 3.47 (m, 4H), 3.40 – 3.36 (m, 2H), 3.11 (s, 3H), 1.70 – 13 1.66 (m, 2H), 1.37 – 1.28 (m, 2H), 0.89 (t, J = 8 Hz, 3H). C NMR (75 MHz, D2O) δ

63.32, 55.14, 49.44, 23.68, 19.06, 12.82. Anal. Calcd for C27H66ClxIyN3O2 (x=2, y=1): C, 44.63; H, 9.16; N, 5.76. Found: C, 44.67; H, 9.36; N, 5.85.

Butyl di(2-hydroxyethyl) methylammonium metal salts

To a solution of chloride salt ([N1,4,2(OH),2(OH)]Cl, 10 mmol) in methanol (20 mL) was added the metal chloride hydrated salt MClY•H2O (0.5 equiv. for CoCl2.6H2O and MnCl2.4H2O, and 0.3 equiv. for GdCl3.6H2O). The reaction mixture was stirred overnight at room temperature. The solvent was evaporated on a rotary evaporator at 50 ºC, and then kept under vacuum for 48 h at 1–4 x 10-2 mbar (rotatory pump) and for 48 h at 6 x 10-5 mbar with stirring at 50 ºC.

Butyl di(2-hydroxyethyl) methylammonium manganese tetrachloride,

[N1,4,2(OH),2(OH)]2[MnCl4], was obtained as a dark brown, high viscous liquid, yield 92.84%;

Anal. Calc. (C18H44Cl3IMnN2O4): C, 33.74; H, 6.92; N, 4.37. Found: C, 33.77; H, 6.92; N,

4.53. [N1,1,6,2(OH)]2[MnCl4], ESI(+)-MS(m/z):176.3 [N1,1,6,2(OH)]. ICP-AES (Mn) 6.73%.

Butyl di(2-hydroxyethyl) methylammonium cobalt tetrachloride,

[N1,4,2(OH),2(OH)]2[CoCl4], was obtained a dark blue, high viscous liquid, yield 95.79%; Anal.

Calc. (C18H44Cl3CoIN2O4): C, 32.62; H, 7.00; N, 4.23. Found: C, 33.48; H, 7.18; N, 4.49.

[N1,1,6,2(OH)]2[CoCl4], ESI(+)-MS(m/z): 176.3 [N1,1,6,2(OH)]. ICP-AES (Co) 9.13%.

Butyl di(2-hydroxyethyl) methylammonium gadolinium hexachloride,

[N1,4,2(OH),2(OH)]3[GdCl6], was obtained a yellow, high viscous liquid, yield 90,12%; Anal.

Calc. (C27H86Cl5GdIN3O16): C, 27.71; H, 7.41; N, 3.59. Found: C, 27.20; H, 7.21; N, 3.72.

[N1,1,6,2(OH)]2[GdCl6], ESI(+)-MS(m/z): 176.3 [N1,1,6,2(OH)]. ICP-AES (Gd) 8.56%.

1,2 General method for chloride based ILs [N1,1,n,2(OH)]Cl

In a closed vessel at room temperature, a solution of N-dimethylethanolamine (12.75 g, 143 mmol) in MeCN (5 mL) was added to the correspondent alkyl chloride (143 mmol) dissolved in MeCN (5 mL), and sodium iodide (2.1 g, 0.143 mmol). The solution was heated at 60ºC overnight. The solvent was removed on a rotary evaporator. The resulting salt was re-dissolved in dichloromethane and the sodium halide removed by filtration.. The solvent was removed on a rotary evaporator, and the obtained salt was stirred under vacuum (<1 mmHg) at 60ºC overnight. The obtained salts were used in the next step without further purification.

General method for magnetic ILs [N1,1,n,2(OH)][MCly] The MILs were prepared using the reported procedures with some modifications.1,2,3 To a solution of chloride salt ([N1,1,n,2(OH)]Cl, 10 mmol) in methanol (20 mL) was added the metal chloride hydrated salt MClY•H2O (1 equiv. for FeCl3.6H2O; 0.5 equiv. for CoCl2.6H2O and

MnCl2.4H2O, and 0.3 equiv. for GdCl3.6H2O). The reaction mixture was stirred overnight at room temperature. The solvent was evaporated on a rotary evaporator at 50 ºC, and then kept under vacuum for 48 h at 1–4 x 10-2 mbar (rotatory pump) and for 48 h at 6 x 10-5 mbar with stirring at 50 ºC.

Hexyl (2-hydroxyethyl) dimethylammonium manganese tetrachloride,

[N1,1,6,2(OH)]2[MnCl4], was obtained as a dark brown liquid, yield 91.32%; Anal.Calc.:

(C20H50Cl3IMnN2O3): C, 36.68; N, 4.28; H, 7.70; Found: C, 36.43; N, 4.32; H, 7.96.

[N1,1,6,2(OH)]2[MnCl4], ESI(+)-MS(m/z):174.3 [N1,1,6,2(OH)]. ICP-AES (Mn) 6.87%.

Octyl (2-hydroxyethyl) dimethylammonium manganese tetrachloride,

[N1,1,8,2(OH)]2[MnCl4], was obtained as a dark brown liquid, yield 99.76%; Anal.Calc.

(C24H58Cl4MnN2O3): C, 46.53; N, 4.52; H, 9.44; Found: C, 46.52; N, 4.40; H, 9.36.

[N1,1,8,2(OH)]2[MnCl4], ESI(+)-MS(m/z):202.4 [N1,1,8,2(OH)]. ICP-AES (Mn) 5.04%

Octyl (2-hydroxyethyl) dimethylammonium cobalt tetrachloride, [N1,1,8,2(OH)]2[CoCl4], was obtained as a dark blue, highly viscous liquid, yield 98.44%. Anal.Calc.

(C24H58.4Cl4CoN2O3.2): C, 45.97; N, 4.47; H, 9.39; Found: C, 45.88; N, 4.72; H, 9.35.

ESI(+)-MS(m/z): 202.4 [N1,1,8,2(OH)]. ICP-AES (Co) 7.85%.

Dodecyl (2-hydroxyethyl) dimethylammonium manganese tetrachloride,

[N1,1,12,2(OH)]2[MnCl4], was obtained as a dark brown solid, yield 95.28%. Anal.Calc.( C32H75Cl4MnN2O3.5): C, 51.89; N, 3.78; H, 10.21; Found: C, 51.75; N, 4.07; H, 10.12.

ESI(+)-MS(m/z):258.5 [N1,1,12,2(OH)]. ICP-AES (Mn) 4.97% Dodecyl (2-hydroxyethyl) dimethylammonium cobalt tetrachloride,

[N1,1,12,2(OH)]2[CoCl4], was obtained as a dark blue, highly viscous liquid, yield 94.75%.

Anal.Calc.( C32H75Cl4CoN2O3.5): C, 51.61; N, 3.76; H, 10.15; Found: C, 51.74; N, 3.68; H,

10.24. ESI(+)-MS(m/z): 258.5 [N1,1,12,2(OH)]. ICP-AES (Co) 9.01%

Fig. S1. Cations and anions used in the design of the MILs studied in this work. -1 Table S2. EC50 values (mg.L ) for MILs under study after 15 minutes of exposure to the luminescent marine bacteria V. fischeri, with the respective 95% confidence limits (in brackets).

-1 EC50 / mg.L at 15 minutes (lower limit; upper limit)

- 2- 2- 3- [FeCl4] [MnCl4] [CoCl4] [GdCl6] 325.96 14.73 37.07 92.34 [N ]+ (202.09 – 1,1,1,2(OH) (13.72 – 15.73) (20.34 – 53.81) (62.15 – 122.52) 449.83) 16.43 [N ]+ n.d. n.d. n.d. 1,1,2,2(OH) (15.11 – 17.71) 17.67 55.49 [N ]+ n.d. n.d. 1,1,6,2(OH) (15.15 – 20.19) (49.70 – 61.28) 17.82 30.93 21.59 [N ]+ n.d. 1,1,8,2(OH) (15.58 – 20.06) (22.90 – 38.97) (17.78 – 25.41) 0.65 0.43 34.35 [N ]+ n.d. 1,1,12,2(OH) (0.55 – 0.75) (0.35 – 0.50) (21.16 – 47.54) 34.68 36.64 29.84 [N ]+ n.d. 1,4,2(OH),2(OH) (33.38 – 35.98) (24.75 – 48.53) (24.41 – 35.26) 502.99 18.55 62.24 62.11 [N ]+ (187.61 – 1,6,2(OH),2(OH) (15.97 – 21.12) (31.70 – 92.78) (54.62 – 69.60) 818.36) 6.50 11.62 18.42 20.76 [N ]+ 6,2(OH),2(OH),2(OH) (5.53 – 7.46) (8.41 – 14.84) (17.36 – 19.47) (17.98 – 23.55) n.d. – not determined

References:

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