Supplementary Material
Isosorbide Spacer Containing Gemini Surfactants: Surface and
Biochemical Study
Kushan Parikh,† Bhavesh Mistry,§ Sarmita Jana,Ϯ Tejal Gajaria,Ϯ Sarita Gupta,§ Ranjitsinh V.
DevkarϮ and Sanjeev Kumar,*
†
Soft Material Research Laboratory, Department of Chemistry, §Department of Biochemistry,
Ϯ
Department of Zoology, Faculty of Science, Department of Applied Chemistry, Faculty of
Technology & Engineering, The Maharaja Sayajirao University of Baroda, Vadodara – 390
001, India.
E-mail: drksanjeev@gmail.com
S1. Synthesis of Gemini Surfactants (7-9):
In a typical esterification procedure (1st step), D-isosorbide (1, 10.23 g, 0.07 mol) in
dichloromethane (25 ml) was added drop wise to a stirred solution of chloroacetylchloride (2,
16.37 g, 0.145 mol) in dichloromethane (50 ml) under N2 atm with screw top pressure tube
(Scheme 1). After complete addition, reaction mixture was stirred for 4 hrs at 50˚C and then
neutralized 3-4 times with Na2CO3 solution. The solvent was removed under high vacuum.
1,4-bischloroacetoxy-D-isosorbate (3) was re-crystallized at least 2-3 times with
ethylacetate:petether (5:5 v/v). Structure of 3 was confirmed by 1H NMR. To get gemini
surfactants by addition reaction, the intermediate (3, 5.98 g, 0.02 mol) was refluxed with
various alkylamines [N,N-dimethyldodecyl-1-amine (4, 8.64 g, 0.04 mol), N,Ndimethyltetradecyl-1-amine (5, 9.77 g, 0.04 mol) and N,N-dimethylhexadecyl-1-amine (6,
10.92 g, 0.04 mol)] in dry ethyl acetate: DCM (8:2) for 24 to 48 hrs under N2 atm with guard
tubing throughout. Reaction completion was confirmed through TLC [CHCl 3: MeOH, 9:1
(v/v); Rf = 0.3 (7-9), 1.3(3)]. After completion of the reaction, solvent was removed under
lower vacuum to get the yellow-whitish mass. The yellow-whitish mass was re-crystallized at
least three times with dry ethyl acetate: DCM: EtOH (8:1.9:0.1 v/v) mixture to obtain the
respective isosorbide based gemini surfactants (7-9).
S2.1 Characterization Data of Spacer 3.
1,4-bischloroacetoxy-D-isosorbate (3, 18.63 g, 89%). White crystalline solid, [α]D30
+137.12 degcm3g−1dm−1 (c=0.1 in CHCl3). FT-IR (Shimadzu 8400S, KBr, cm-1) neat: 2991
(CH), 2881 (CH), 1751 (C=O), 1462 (CH) and 1193 (C-O). 1H NMR (400 MHz Bruker;
CDCl3; TMS):  3.93-3.96 (m, 2H, CH2), 4.03-4.04 (d, 2H, CH2), 4.10 (s, 2H, CH2), 4.15
(s, 2H, CH2), 4.53-4.55 (d, 1H, CH), 4.91-4.94 (t, 1H, CH), 5.27-5.31 (m, 2H, CH). MS
(m/z): 146.93 (M-ClCH2COOH), 109.93 (stable compound of 2,5-dihydrofuro[3,2-b]furan),
76.89 (M-ClCH2CO-), 48.94 (M-ClCH2+).
S2.2 Characterization Data of gemini surfactants (7-9).
D-isosorbate-1,4-diyl bis(N,N-dimethyl-N-dodecyl-ammoniumacetoxy) dichloride (7,
6.68 g, 46%). White solid (highly hygroscopic), [α]D30 +30.08 degcm3g−1dm−1 (c=0.1 in
CHCl3). Elemental (CHN) Analyses, Found: C, 59.9; H, 10.4; N, 3.6. Anal. Calculated for
C38H74Cl2N2O6·2H2O: C, 59.9; H, 10.3; N, 3.6(%).FT-IR (Shimadzu 8400S, KBr, cm-1): neat
2919 (CH), 2853 (CH), 1750 (C=O), 1469 (CH), 1243 (CN), 1203 (C-O) and 1092. 1H NMR
(400 MHz Bruker; CDCl3; TMS): δ 0.91 (t, 6H, (CH3)2), 1.24 (s, 32H, (CH2)16), 1.36 (s, 4H,
(CH2)2), 1.76 (s, 4H, (CH2)2), 3.53 (s, 6H, (CH3)2), 3.60-3.64 (d, 6H, (CH3)2), 3.77-3.99
(m, 6H, CH and CH2), 4.08 (d, 1H, CH), 4.15 (s, 1H, CH), 4.62 (s, 1H, CH), 4.84-4.88 (d,
1H, CH), 5.03 (s, 1H, CH), 5.22-5.37 (m, 4H, (CH2)2), 5.47 (d, 1H, CH). ESI-MS (m/z,
725.910 gm/mole): 689.6 (M-Cl-), 653.6 (M-2Cl-), 639.6 (M-2Cl-, CH3), 485.4 (M-C12H25,
2Cl-), 400.4 (M-C12H25N+(CH3)2CH2CO-, 2Cl-).
D-isosorbate-1,4-diyl bis(N,N-dimethyl-N-tetradecyl-ammoniumacetoxy) dichloride
(8, 9.70 g, 62%). White crystalline solid, [α]D30 +28.50 degcm3g−1dm−1 (c=0.1 in CHCl3).
Elemental (CHN) Analyses, Found: C, 63.8; H, 10.7; N, 3.5. Anal. Calculated for
C42H82Cl2N2O6·0.5H2O: C, 63.7; H, 10.6; N, 3.5(%).FT-IR (Shimadzu 8400S, KBr, cm-1)
neat: 2916 (CH), 2851 (CH), 1749 (C=O), 1470 (CH), 1257 (CN), 1204 (C-O) and 1095. 1H
NMR (400 MHz Bruker; CDCl3; TMS): δ 0.86-0.88 (t, 6H, (CH3)2), 1.25 (s, 40H, (CH2)20),
1.34 (s, 4H, (CH2)2), 1.74 (s, 4H, (CH2)2), 3.52 (dd, 6H, (CH3)2), 3.59-3.63 (d, 6H, (CH3)2),
3.71-3.97 (m, 6H, CH and CH2), 4.06-4.12 (q, 2H, CH2), 4.59 (s, 1H, CH), 4.89-4.93 (d, 1H,
CH), 4.99 (s, 1H, CH), 5.26-5.34 (m, 4H, CH2), 5.51-5.55 (d, 1H, CH). ESI-MS (m/z,
782.016 gm/mole): 745.7 (M-Cl-), 709.7 (M-2Cl-), 695.7 (M-2Cl-, CH3), 428.4 (MC14H29N+(CH3)2CH2CO, 2Cl-), 314.3 (M-[C14H29, Cl-]2), 257.2 (M-[C14H29N+(CH3)2]2, 2Cl-).
D-isosorbate-1,4-diyl bis(N,N-dimethyl-N-hexadecyl-ammoniumacetoxy) dichloride
(9, 11.89 g, 71%). White crystalline solid, [α]D30 +26.16 degcm3g−1dm−1 (c=0.1 in CHCl3).
Elemental (CHN) Analyses, Found: C, 66.6 H, 10.8; N, 3.3. Anal. Calculated for
C46H90Cl2N2O6: C, 65.9; H, 10.8; N, 3.3(%).FT-IR (Shimadzu 8400S, KBr, cm-1) neat: 2917
(CH), 2849 (CH), 1748 (C=O), 1470 (CH), 1256 (CN) and 1203 (C-O). 1H NMR (400 MHz
Bruker; CDCl3; TMS): δ 0.87-0.90 (t, 6H, (CH3)2), 1.25 (s, 48H, (CH2)24), 1.35 (s, 4H,
(CH2)2), 1.76 (s, 4H, (CH2)2), 3.52-3.53 (dd, 6H, (CH3)2), 3.60-3.64 (d, 6H, (CH3)2), 3.763.92 (m, 5H, (CH2)2 and CH), 3.96-3.99 (d, 1H, CH), 4.04-4.07 (d, 1H, CH), 4.12-4.15 (d,
1H, CH), 4.61-4.62 (d, 1H, CH), 4.86-4.90 (d, 1H, CH), 5.0-5.03 (t, 1H, CH), 5.25-5.36 (m,
4H, (CH2)2), 5.50-5.55 (d, 1H, CH). ESI-MS (m/z, 838.122 gm/mole): 801.2 (M-Cl-), 765.3
(M-2Cl-), 541.4 (M-C16H33, 2Cl), 328.6 (C16H33N+(CH3)2CH2COOH), 317.4 (M-C32H66, 2Cl), 270.6 (C16H33N(CH3)2).
120
100
80
80
0
'C
on
tro
l
'1
3.
78
'5
50
.5
9
'6
88
.2
4
0
'2
75
.3
'4
12
.9
5
20
'6
8.
82
'1
37
.6
5
20
[Gemini 7] / M
IC50 = 42.58 M
(c)
80
80
% Cell Viability
100
60
40
(d)
60
40
100
80
80
'1
27
.7
8
'1
02
.7
8
'7
6.
67
'5
1.
12
[Gemini 9] / M
'1
19
.2
4
'C
on
t ro
l
'8
.9
4
'5
.9
6
'2
.9
8
'1
.1
9
0
'0
.8
9
0
'0
.6
20
'0
.1
2
'2
5.
56
40
20
[Gemini 9] / M
(f)
60
'2
9.
81
40
IC50 = 20.03 M
'1
1.
92
% Cell Viability
100
60
'1
2.
78
120
'5
9.
62
(e)
'5
.9
6
IC50 = 2.98 M
[Gemini 8] / M
'1
.1
9
120
'C
on
tro
l
[Gemini 8] / M
'6
38
.9
4
'1
27
7.
87
'6
3.
89
'1
27
.7
9
'3
1.
95
'1
2.
78
0
'1
.2
8
'C
on
t ro
l
IC50 = 52.94 M
20
0
'C
on
tro
l
[Gemini 7] / M
120
100
20
% Cell Viability
40
'3
44
.4
0
40
(b)
60
'2
06
.6
4
'2
75
.5
2
60
IC50 = 111.69 M
'1
02
.5
'1
37
.7
6
% Cell Viability
100
120
% Cell Viability
(a)
'6
8.
88
IC50 = 276.19 M
'C
on
tro
l
'1
3.
76
% Cell Viability
120
Fig. S1 % Cell viability vs concentration (µM) of GSs (7-9) for determination of IC50 values
on A549 and L132 cells: (a), (c) and (e) represents cell viability on A549; (b), (d) and (f)
represents cell viability on L132, respectively.