Apparatus and analysis
The Stuart Scientific SMP1 apparatus (Stuart, Red Hill, UK) was used in recording of the uncorrected melting points.
The SHIMADZU FTIR-8400S spectrometer (SHIMADZU, Boston, MA, USA) was used on the IR measurement.
The Bruker spectrometer (400 and 600 MHz, Brucker, Fällanden, Switzerland) was used in the NMR analysis using Tetramethylsilane (TMS) (0.00 ppm) as an internal standard.
The Finnigan LCQ and Finnigan MAT 95XL spectrometers (Finnigan, Darmstadt, Germany) were used in the ESI and EI measurement, respectively.
The Kunshan KQ-250B ultrasound cleaner (50 kHz, 240 W, Kunshan Ultrasonic Instrument, Kunshan, China) was used for carrying out all reactions.
General alkylation procedure for the synthesis of cationic amphiphilic fluorinated pyridinium hydrazones 2–9
Conventional method (CM)
To a mixture of pyridine hydrazone 1 (1 mmol) in acetonitrile (30 ml) was added an appropriate long alkyl iodides with chain ranging from C8 to C18 (1.5 mmol) under stirring. The mixture was refluxed for 72 h, then the solvent was reduced under pressure. The obtained solid was collected by filtration and washed with acetonitrile to give the target ILs 2–9.
Ultrasound method (US)
To a mixture of pyridine hydrazone 1 (1 mmol) in acetonitrile (30 ml) was added an appropriate long alkyl iodides with chain ranging from C8 to C18 (1.5 mmol) under stirring. The mixture was irradiated by ultrasound irradiation for 10–12 h. The reaction was processed as described above to give the same target ILs 2–9.
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-octylpyridin-1-ium iodide (
2
)
It was obtained as yellow crystals; mp: 104–105 °C. FT-IR (KBr), cm−1: ῡ = 1595 (C=N), 1670 (C=O), 2870, 2960 (Al–H), 3071 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.32 (m, 10H, 5× CH2), 1.94–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.47 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 21.99, 25.36, 25.41, 28.30, 28.40, 30.50, 30.63, 31.08 (6×CH2), 60.95, 61.02 (NCH2), 115.74, 115.95, 116.17, 126.14, 127.11, 129.36, 129.44, 129.73, 129.81, 130.21, 130.24, 145.08, 145.67, 147.33, 149.36, 149.63 (Ar–C), 158.76, 162.28, 164.75, 165.21 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.72 to − 109.65), (− 109.20 to − 109.12) (2m, 1F, Ar–F). MS (ES) m/z = 483.32 [M+].
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-nonylpyridin-1-ium iodide (
3
)
It was obtained as yellow crystals; mp: 91–93 °C. FT-IR (KBr), cm−1: ῡ= 1598 (C=N), 1682 (C=O), 2872, 2969 (Al–H), 3078 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.32 (m, 12H, 6× CH2), 1.94–1.99 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.37 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.15 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.46 (s, 0.75H, CONH), 12.51 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.92 (CH3), 22.03, 25.36, 25.41, 28.35, 28.52, 28.70, 30.51, 30.64, 31.18 (7×CH2), 60.93, 61.01 (NCH2), 115.74, 115.96, 116.18, 126.15, 127.11, 129.35, 129.43, 129.73, 129.82, 130.20, 130.23, 145.06, 145.69, 147.31, 149.33, 149.64 (Ar–C), 158.75, 162.28, 164.76, 165.23 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.94 to − 109.86), (− 109.42 to − 109.34) (2m, 1F, Ar–F). MS (ES) m/z = 497.10 [M+].
1-Decyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium iodide (
4
)
It was obtained as yellow crystals; mp: 110–112 °C. FT-IR (KBr), cm−1: ῡ = 1615 (C=N), 1690 (C=O), 2873, 2966 (Al–H), 3074 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.32 (m, 14H, 7× CH2), 1.94–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.23 (t, 0.5H, J = 8 Hz, Ar–H), 7.38 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.34 (d, 1.5H, J = 8 Hz, Ar–H), 12.48 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 12.40, 12.42 (CH3), 20.55, 23.85, 23.89, 26.84, 27.11, 27.24, 27.28, 27.32, 28.99, 29.13, 29.72 (8×CH2), 59.42, 59.49 (NCH2), 114.24, 114.46, 114.68, 124.63, 125.59, 127.84, 127.92, 128.22, 128.31, 128.55, 128.68, 128.71, 143.54, 144.18, 145.78, 147.80, 148.12 (Ar–C), 157.25, 160.77, 163.24, 163.73 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.94 to − 109.85), (− 109.42 to − 109.34) (2m, 1F, Ar–F). MS (ES) m/z = 511.05 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-undecylpyridin-1-ium iodide (
5
)
It was obtained as yellow crystals; mp: 82–83 °C. FT-IR (KBr), cm−1: ῡ = 1598 (C=N), 1677 (C=O), 2872, 2967 (Al–H), 3078 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.32 (m, 16H, 8× CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.34 (d, 1.5H, J = 8 Hz, Ar–H), 12.45 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 12.39 (CH3), 20.53, 23.86, 26.83, 27.13, 27.23, 27.37, 27.40, 28.98, 29.12, 29.74 (9×CH2), 59.46, 59.53 (NCH2), 114.23, 114.44, 114.66, 124.63, 125.61, 127.85, 127.93, 128.22, 128.31, 128.53, 128.56, 128.71, 128.74, 143.58, 144.18, 145.82, 147.88, 148.15 (Ar–C), 157.23, 160.78, 163.26, 163.69 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.95 to − 109.88), (− 109.35 to − 109.37) (2m, 1F, Ar–F). MS (ES) m/z = 525.10 [M+].
1-Dodecyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium iodide (
6
)
It was obtained as yellow crystals; mp: 72–73 °C. FT-IR (KBr), cm−1: ῡ = 1605 (C=N), 1688 (C=O), 2883, 2961 (Al–H), 3074 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.32 (m, 18H, 9× CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.70 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.34 (d, 1.5H, J = 8 Hz, Ar–H), 12.46 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 11.54, 11.59 (CH3), 19.68, 23.00, 25.98, 26.30, 26.38, 26.51, 26.60, 28.13, 28.27, 28.88 (10× CH2), 58.60, 58.67 (NCH2), 113.37, 113.59, 113.80, 123.78, 124.75, 127.00, 127.08, 127.36, 127.45, 127.86, 127.89, 142.72, 143.33, 144.97, 147.02, 127.29 (Ar–C), 156.38, 159.93, 162.40, 162.83 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.95 to − 109.88), (− 109.44 to − 109.36) (2m, 1F, Ar–F). MS (ES) m/z = 539.40 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-tetradecylpyridin-1-ium iodide (
7
)
It was obtained as yellow crystals; mp: 86–88 °C. FT-IR (KBr), cm−1: ῡ = 1590 (C=N), 1679 (C=O), 2878, 2964 (Al–H), 3078 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.86 (m, 3H, CH3), 1.24–1.32 (m, 22H, 11× CH2), 1.94–1.98 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.44 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 22.03, 25.36, 27.80, 28.34, 28.65, 28.74, 28.86, 28.96, 28.99, 29.77, 30.48, 30.62, 31.24, 32.85 (12×CH2), 60.96, 61.03 (NCH2), 115.73, 115.94, 116.16, 126.13, 127.11, 129.34, 129.43, 129.72, 129.81, 130.21, 130.24, 145.08, 145.68, 147.31, 149.38, 149.65 (Ar–C), 158.73, 162.29, 164.29, 165.18 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.96 to − 109.89), (− 109.44 to − 109.36) (2m, 1F, Ar–F). MS (ES) m/z = 567.20 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-hexadecylpyridin-1-ium iodide (
8
)
It was obtained as yellow crystals; mp: 78–80 °C. FT-IR (KBr), cm−1: ῡ = 1610 (C=N), 1677 (C=O), 2887, 2969 (Al–H), 3076 (Ar–H). 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.86 (m, 3H, CH3), 1.23–1.30 (m, 26H, 13× CH2), 1.96–1.98 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.34 (d, 1.5H, J = 4 Hz, Ar–H), 12.45 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.36, 28.34, 28.64, 28.74, 28.87, 28.96, 29.00, 30.49, 30.62, 31.24 (12×CH2), 60.96, 61.03 (NCH2), 115.73, 115.94, 116.16, 126.14, 127.11, 129.34, 129.43, 129.72, 129.81, 130.04, 130.24, 145.08, 145.69, 147.31, 149.37 (Ar–C), 158.72, 162.29, 164.76, 165.18 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.97 to − 109.89), (− 109.45 to − 109.37) (2m, 1F, Ar–F). MS (ES) m/z = 595.30 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-octadecylpyridin-1-ium iodide (
9
)
It was obtained as yellow crystals; mp: 98–99 °C. FT-IR (KBr), cm−1: ῡ= 1612 (C=N), 1678 (C=O), 2887, 2955 (Al–H), 3086 (Ar–H). 1H NMR (400 MHz, CDCl3): δH = 0.79–0.82 (m, 3H, CH3), 1.16–1.20 (m, 30H, 15× CH2), 1.96–2.00 (m, 2H, NCH2CH2), 4.78 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 6.97 (t, 2H, J = 8 Hz, Ar–H), 7.71 (dd, 2H, J = 4 Hz, 8 Hz, Ar–H), 8.87 (d, 2H, J = 4 Hz, Ar–H), 9.08 (s, 1H, H–C=N), 9.12 (d, 2H, J = 8 Hz, Ar–H), 12.18 (bs, 1H, CONH). 13C NMR (100 MHz, CDCl3): δC = 14.08 (CH3), 22.66, 26.10, 28.96, 29.31, 29.33, 29.48, 29.57, 29.63, 29.68, 31.67, 31.90 (16× CH2), 62.74 (NCH2), 115.85, 116.07, 127.88, 129.47, 130.14, 130.22, 144.82, 147.91, 151.67 (Ar–C), 158.57, 163.22, 163.25, 165.76 (C=N, C=O). 19F NMR (377 MHz, CDCl3): δF = (− 107.98 to − 107.89), (− 107.72 to − 107.65) (2 m, 1F, Ar–F). MS (ES) m/z = 623.30 [M+].
General metathesis procedure for the synthesis of pyridinium hydrazones 10–33
Conventional method (CM)
A mixture of equimolar of IL 2–9 (1 mmol) and fluorinated metal salt (KPF6, NaBF4 and/or NaCF3COO) (1 mmol) in dichloromethane (15 ml) was heated under reflux for 12 h. After cooling, the solid formed was collected by extraction and/or by filtration. The solid was washed by dichloromethane to afford the task-specific ILs 10–33.
Ultrasound method (US)
A mixture of equimolar of IL 2–9 (1 mmol) and fluorinated metal salt (KPF6, NaBF4 and/or NaCF3COO) (1 mmol) in dichloromethane (15 ml) was irradiated by ultrasound irradiation for 6 h. The reaction was processed as described above to give the same task-specific ILs 10–33.
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-octylpyridin-1-ium hexafluorophosphate (
10
)
It was obtained as yellow crystals; mp: 64–65 °C. 1H NMR (400 MHz, DMSO-d6): δH = 0.82–0.88 (m, 3H, CH3), 1.26–1.30 (m, 10H, 5×CH2), 1.94–2.00 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.26 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.38 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.50 (bs, 1H, CONH).13C NMR (100 MHz, DMSO-d6): δC = 13.09 (CH3), 22.00, 25.36, 25.41, 28.30, 28.40, 30.51, 30.64, 31.09 (6×CH2), 60.95, 61.02 (NCH2), 115.75, 115.96, 116.18, 126.14, 127.11, 129.35, 129.44, 129.73, 129.81, 130.05, 130.24, 130.24, 145.06, 145.67, 147.35, 149.35, 149.63 (Ar–C), 158.78, 162.28, 164.75, 165.22 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 152.70 to − 135.29 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.98 (d, 6F, PF6), (− 109.72 to − 109.65), (− 109.20 to − 109.12) (2m, 1F, Ar–F). MS (ES) m/z = 501.20 [M+].
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-octylpyridin-1-ium tetrafluoroborate (
11
)
It was obtained as yellow crystals; mp: 80–82 °C. 1H NMR (400 MHz, DMSO-d6): δH = 0.84–0.88 (m, 3H, CH3), 1.26–1.31 (m, 10H, 5×CH2), 1.95–2.00 (m, 2H, NCH2CH2), 4.70 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.26 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.38 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.63 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.90 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.41 (d, 0.5H, J = 8 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 4 Hz, Ar–H), 9.27 (d, 0.5H, J = 8 Hz, Ar–H), 9.36 (d, 1.5H, J = 8 Hz, Ar–H), 12.49 (s, 0.75H, CONH), 12.53 (s, 0.25H, CONH).13C NMR (100 MHz, DMSO-d6): δC = 13.87 (CH3), 21.97, 25.32, 25.38, 28.27, 28.37, 28.40, 30.48, 30.61, 31.06 (6× CH2), 60.89, 60.96 (NCH2), 115.71, 115.92, 116.14, 126.10, 127.07, 129.33, 129.41, 129.69, 129.78, 130.01, 130.15, 130.18, 145.02, 145.65, 147.23, 149.28, 149.57 (Ar–C), 158.72, 161.89, 162.23, 164.70, 165.19 (C=N, C=O).11B NMR (128 MHz, DMSO-d6): δB = − 1.31 to − 1.30 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.82 to − 109.74), (− 109.29 to − 109.21) (2m, 1F, Ar–F); − 148.12, − 148.07 (2d, 4F, BF4). MS (ES) m/z = 443.20 [M+].
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-octylpyridin-1-ium trifluoroacetate (
12
)
It was obtained as yellow crystals; mp: 74–76 °C. 1H NMR (400 MHz, DMSO-d6): δH = 0.84–0.88 (m, 3H, CH3), 1.26–1.30 (m, 10H, 5×CH2), 1.95–1.97 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.26 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.35 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 4 Hz, Ar–H), 8.49 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.32 (d, 1.5H, J = 8 Hz, Ar–H), 12.54 (bs, 1H, CONH).13C NMR (100 MHz, DMSO-d6): δC = 13.85 (CH3), 21.95, 25.30, 25.35, 28.25, 28.35, 28.38, 30.46, 30.58, 31.03 (6× CH2), 60.85, 60.88 (NCH2), 115.69, 115.88, 116.10, 126.05, 127.04, 129.28, 129.36, 129.61, 129.70, 129.99, 130.24, 130.27, 144.98, 145.54, 147.59, 149.20, 149.56 (Ar–C), 158.84, 162.15, 165.19 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.50 (s, 3F, CF3), (− 109.92 to − 109.84), (− 109.53 to − 109.45) (2m, 1F, Ar–F). MS (ESI) m/z = 467.10 [M+ + 1].
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-nonylpyridin-1-ium hexafluorophosphate (
13
)
It was obtained as yellow crystals; mp: 69–70 °C. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.30 (m, 12H, 6×CH2), 1.94–1.99 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.37 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.15 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 8 Hz, Ar–H), 9.24 (d, 0.5H, J = 4 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.51 (s, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.92 (CH3), 22.03, 25.36, 25.41, 28.35, 28.52, 28.70, 28.74, 30.51, 30.64, 31.18 (7×CH2), 60.93, 61.01 (NCH2), 115.74, 115.96, 116.18, 126.16, 127.11, 129.34, 129.43, 129.72, 129.81, 130.21, 130.24, 145.06, 145.68, 147.30, 149.34 (Ar–C), 158.75, 162.28, 164.75, 165.23 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 152.98 to − 135.42 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.21 (d, 6F, PF6), (− 109.94 to − 109.86), (− 109.42 to − 109.34) (2m, 1F, Ar–F). MS (ES) m/z = 515.20 [M+].
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-nonylpyridin-1-ium tetrafluoroborate (
14
)
It was obtained as yellow crystals; mp: 88–90 °C. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.30 (m, 12H, 6×CH2), 1.95–1.99 (m, 2H, NCH2CH2), 4.67 (t, 2H, J = 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.35 (t, 1.5H, J = 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.15 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.24 (d, 0.5H, J = 8 Hz, Ar–H), 9.32 (d, 1.5H, J = 8 Hz, Ar–H), 12.49 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.92 (CH3), 22.03, 25.36, 28.35, 28.52, 28.70, 30.51, 30.64, 31.18 (7×CH2), 60.94, 61.02 (NCH2), 115.74, 115.97, 116.19, 126.16, 127.11, 129.34, 129.43, 129.72, 129.81, 130.21, 145.07, 145.68, 147.32, 149.34 (Ar–C), 158.75, 162.29, 164.76, 165.24 (C=N, C=O).11B NMR (128 MHz, DMSO-d6): δB = − 1.31 to − 1.30 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.94 to − 109.86), (− 109.42 to − 109.34) (2m, 1F, Ar–F); − 148.29, − 148.24 (2d, 4F, BF4). MS (ES) m/z = 457.15 [M+].
4-(2-(4-Fluorobenzylidene) hydrazinecarbonyl)-1-nonylpyridin-1-ium trifluoroacetate (
15
)
It was obtained as yellow crystals; mp: 96–98 °C. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (t, 3H, J = 4 Hz, CH3), 1.25–1.30 (m, 12H, 6×CH2), 1.94–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.37 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.50 (s, 0.75H, CONH), 12.51 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.91 (CH3), 22.03, 25.36, 28.34, 25.41, 28.34, 28.52, 28.70, 28.73, 30.51, 30.64, 31.18 (7×CH2), 60.93, 61.00 (NCH2), 115.74, 115.96, 116.18, 126.15, 127.11, 129.34, 129.43, 129.80, 130.04, 130.21, 130.24, 145.07, 145.69, 147.31, 149.35, 149.65 (Ar–C), 158.75, 162.28, 164.75, 165.23 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.50 (s, 3F, CF3), (− 109.96 to − 109.88), (− 109.44 to − 109.36) (2 m, 1F, Ar–F). MS (ES) m/z = 483.20 [M+].
1-Decyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium hexafluorophosphate (
16
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.88 (m, 3H, CH3), 1.25–1.30 (m, 14H, 7×CH2), 1.95–1.98 (m, 2H, NCH2CH2), 4.67 (t, 2H, J = 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.35 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.23 (d, 0.5H, J = 4 Hz, Ar–H), 9.31 (d, 1.5H, J = 8 Hz, Ar–H), 12.48 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.90 (CH3), 22.04, 25.36, 25.40, 28.33, 28.60, 28.74, 28.77, 28.82, 30.50, 30.63, 31.23 (8×CH2), 60.96, 61.06 (NCH2), 115.72, 115.95, 116.16, 126.15, 127.12, 129.32, 129.41, 129.72, 129.81, 130.07, 130.21, 130.24, 145.05, 145.67, 147.34, 149.36, 149.67, (Ar–C), 158.75, 162.28, 164.77, 165.22 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 157.37 to − 131.02 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.22 (d, 6F, PF6), (− 109.94 to − 109.85), (− 109.42 to − 109.34) (2m, 1F, Ar–F). MS (ES) m/z = 529.70 [M+].
1-Decyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium tetrafluoroborate (
17
)
It was obtained as colorless syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.30 (m, 14H, 7×CH2), 1.95–1.98 (m, 2H, NCH2CH2), 4.67 (t, 2H, J = 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.35 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.52 (s, 0.75H, H–C=N), 8.55 (d, 1.5H, J = 8 Hz, Ar–H), 9.24 (d, 0.5H, J = 4 Hz, Ar–H), 9.32 (d, 1.5H, J = 4 Hz, Ar–H), 12.52 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.90, 13.91 (CH3), 22.05, 25.36, 25.40, 28.34, 28.61, 28.75, 28.78, 28.83, 30.50, 30.63, 31.23, (8×CH2), 60.94, 61.01 (NCH2), 115.74, 115.96, 116.18, 126.16, 127.11, 129.34, 129.42, 129.71, 129.80, 130.07, 130.23, 130.26, 145.07, 145.67, 147.34, 149.35 (Ar–C), 158.76, 162.28, 164.75, 165.23, (C=N, C=O). 11B NMR (128 MHz, DMSO-d6): δB = − 1.31 to − 1.29 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.94 to − 109.88), (− 109.44 to − 109.36) (2m, 1F, Ar–F); − 148.30, − 148.24 (2d, 4F, BF4). MS (ES) m/z = 471.60 [M+].
1-Decyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium trifluoroacetate (
18
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.25–1.30 (m, 14H, 7×CH2), 1.95–1.98 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.25 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.37 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.17 (s, 0.25H, H–C=N), 8.40 (d, 0.5H, J = 8 Hz, Ar–H), 8.52 (s, 0.75H, H–C=N), 8.55 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.56 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89, 13.91 (CH3), 22.05, 25.36, 25.40, 28.34, 28.61, 28.74, 28.78, 28.82, 30.50, 30.64, 31.23 (8×CH2), 60.94, 60.98 (NCH2), 115.74, 115.95, 116.16, 126.13, 127.11, 129.33, 129.42, 129.69, 129.77, 130.07, 130.28, 130.31, 145.07, 145.65, 147.48, 149.35 (Ar–C), 158.82, 162.25, 164.73, 165.23 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.52 (s, 3F, CF3), (− 109.95 to − 109.87), (− 109.50 to − 109.42) (2m, 1F, Ar–F). MS (ES) m/z = 497.33 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-undecylpyridin-1-ium hexafluorophosphate (
19
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.30 (m, 16H, 8×CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.36 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.53 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 4 Hz, Ar–H), 9.24 (d, 0.5H, J = 4 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.51 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.90 (CH3), 22.04, 25.36, 28.34, 28.64, 28.74, 28.87, 28.91, 30.49, 30.63, 31.24 (9×CH2), 60.95, 61.03 (NCH2), 115.73, 115.95, 116.17, 126.16, 127.11, 129.34, 129.42, 129.71, 128.80, 130.07, 130.26, 145.08, 145.67, 147.32, 149.38, 149.66 (Ar–C), 158.73, 162.28, 164.76, 165.20 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 152.97 to − 135.41 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.24 (d, 6F, PF6), (− 109.95 to − 109.88), (− 109.35 to − 109.37) (2m, 1F, Ar–F). MS (ES) m/z = 543.40 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-undecylpyridin-1-ium tetrafluoroborate (
20
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.30 (m, 16H, 8×CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.17 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.56 (s, 0.75H, H–C=N), 8.58 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.34 (d, 1.5H, J = 8 Hz, Ar–H), 12.52 (s, 0.25H, CONH), 12.64 (s, 0.75H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 22.03, 25.36, 28.34, 28.64, 28.73, 28.87, 28.91, 30.49, 30.63, 31.24 (9×CH2), 60.95, 61.01 (NCH2), 115.73, 115.94, 116.16, 126.19, 127.10, 129.34, 129.43, 129.69, 129.78, 130.07, 130.25, 130.28, 145.08, 145.66, 147.25, 149.40, 149.66 (Ar–C), 158.70, 162.27, 164.74, 165.19 (C=N, C=O). 11B NMR (128 MHz, DMSO-d6): δB = − 1.30 to − 1.28 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.97 to − 109.89), (− 109.48 to − 109.40) (2m, 1F, Ar–F); − 148.36, − 148.30 (2d, 4F, BF4). MS (ES) m/z = 485.20 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-undecylpyridin-1-ium trifluoroacetate (
21
)
It was obtained as colorless syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.30 (m, 16H, 8×CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.36 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.87 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.32 (d, 1.5H, J = 4 Hz, Ar–H), 12.54 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 22.03, 25.36, 28.33, 28.64, 28.73, 28.87, 28.91, 30.49, 30.63, 31.24 (9×CH2), 60.96, 60.99 (NCH2), 115.73, 115.93, 116.15, 126.12, 127.11, 129.34, 129.42, 129.67, 129.76, 130.05, 130.30, 130.33, 145.07, 145.63, 147.55, 149.38, 149.67 (Ar–C), 158.82, 162.25, 164.72, 165.20 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.53 (s, 3F, CF3), (− 109.97 to − 109.89), (− 109.54 to − 109.46) (2 m, 1F, Ar–F). MS (ES) m/z = 511.30 [M+].
1-Dodecyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium hexafluorophosphate (
22
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.30 (m, 18H, 9×CH2), 1.96–1.98 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.37 (dd, 1.5H, J = 8 Hz, 12 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.24 (d, 0.5H, J = 4 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.47 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 22.03, 25.36, 28.33, 28.65, 28.73, 28.86, 28.95, 30.48, 30.62, 31.24 (10×CH2), 60.96, 61.03 (NCH2), 115.73, 115.95, 116.17, 126.14, 127.11, 129.34, 129.43, 129.72, 129.81, 130.04, 130.25, 145.09, 145.68, 147.34, 149.38, 149.66 (Ar–C), 158.74, 162.29, 164.76, 165.20 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 157.37 to − 131.02 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.25 (d, 6F, PF6), (− 109.95 to − 109.88), (− 109.44 to − 109.36) (2m, 1F, Ar–F). MS (ES) m/z = 557.30 [M+].
1-Dodecyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium tetrafluoroborate (
23
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83 (t, 3H, J = 8 Hz, CH3), 1.24–1.30 (m, 18H, 9×CH2), 1.96–1.98 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.52 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.48 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 22.03, 25.36, 28.33, 28.65, 28.74, 28.86, 28.95, 30.48, 30.62, 31.24 (10×CH2), 60.96, 61.03 (NCH2), 115.73, 115.94, 116.16, 126.15, 127.11, 129.34, 129.43, 129.72, 129.80, 130.22, 130.25, 145.08, 145.69, 147.32, 149.38, 149.66 (Ar–C), 158.73, 162.29, 164.76, 165.19 (C=N, C=O). 11B NMR (128 MHz, DMSO-d6): δB = − 1.31 to − 1.28 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.96 to − 109.88), (− 109.45 to − 109.37) (2m, 1F, Ar–F); − 148.36, − 148.30 (2d, 4F, BF4). MS (ES) m/z = 499.20 [M+].
1-Dodecyl-4-(2-(4-fluorobenzylidene) hydrazinecarbonyl)pyridin-1-ium trifluoroacetate (
24
)
It was obtained as colorless syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.85 (t, 3H, J = 8 Hz, CH3), 1.24–1.30 (m, 18H, 9×CH2), 1.96–1.98 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.53 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 4 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.51 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.89 (CH3), 22.03, 25.36, 28.33, 28.65, 28.73, 28.86, 28.95, 30.48, 30.63, 31.24 (10×CH2), 60.96, 61.01 (NCH2), 115.73, 115.94, 116.16, 126.14, 127.11, 129.34, 129.43, 129.70, 129.79, 130.25, 130.28, 145.08, 145.67, 147.37, 149.39, 149.66 (Ar–C), 158.75, 162.27, 164.75, 165.19 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.53 (s, 3F, CF3), (− 109.97 to − 109.89), (− 109.48 to − 109.40) (2m, 1F, Ar–F). MS (ES) m/z = 525.20 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-tetradecylpyridin-1-ium hexafluorophosphte (
25
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.24–1.30 (m, 22H, 11×CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.24 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.44 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.36, 28.33, 28.65, 28.73, 28.86, 28.95, 28.99, 30.48, 30.62, 31.24, 32.84 (12×CH2), 60.97, 61.04 (NCH2), 115.73, 115.94, 116.16, 126.14, 127.11, 129.34, 129.43, 129.72, 129.81, 130.07, 130.21, 130.24, 145.07, 145.68, 147.32, 149.38 (Ar–C), 158.73, 162.29, 164.77, 165.19 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 152.97 to − 135.41 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.26 (d, 6F, PF6), (− 109.96 to − 109.89), (− 109.44 to − 109.36) (2m, 1F, Ar–F). MS (ES) m/z = 585.50 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-tetradecylpyridin-1-ium tetrafluoroborate (
26
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.85 (t, 3H, J = 8 Hz, CH3), 1.24–1.30 (m, 22H, 11×CH2), 1.96–1.99 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.50 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.44 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.36, 28.34, 28.65, 28.74, 28.87, 28.96, 28.99, 30.48, 30.62, 31.24 (12×CH2), 60.96, 61.03 (NCH2), 115.73, 115.94, 116.16, 126.14, 127.11, 129.34, 129.43, 129.72, 129.81, 130.07, 130.21, 130.24, 145.08, 145.69, 147.32, 149.38, 149.66 (Ar–C), 158.72, 162.29, 164.77, 165.19 (C=N, C=O). 11B NMR (128 MHz, DMSO-d6): δB = − 1.30 to − 1.29 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.97 to − 109.89), (− 109.45 to − 109.37) (2m, 1F, Ar–F); − 148.37, − 148.32 (2d, 4F, BF4). MS (ES) m/z = 527.40 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-tetradecylpyridin-1-ium trifluoroacetate (
27
)
It was obtained as colorless syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.85 (t, 3H, J = 8 Hz, CH3), 1.24–1.30 (m, 22H, 11×CH2), 1.96–1.98 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.47 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.36, 28.33, 28.65, 28.74, 28.86, 28.95, 28.99, 30.49, 30.62, 31.24 (12×CH2), 60.95, 61.03 (NCH2), 115.72, 115.94, 116.16, 126.14, 127.11, 129.34, 129.43, 129.71, 129.80, 130.22, 130.25, 145.08, 145.69, 147.32, 149.38, 149.66 (Ar–C), 158.73, 162.29, 164.76, 165.19 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.55 (s, 3F, CF3), (− 109.97 to − 109.89), (− 109.45 to − 109.38) (2m, 1F, Ar–F). MS (ES) m/z = 553.30 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-hexadecylpyridin-1-ium hexaflurophosphate (
28
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.88 (m, 3H, CH3), 1.23–1.30 (m, 26H, 13×CH2), 1.96–2.00 (m, 2H, NCH2CH2), 4.68 (t, 2H, J = 8 Hz, NCH2), 7.24 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.89 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 4 Hz, Ar–H), 12.44 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.36, 28.34, 28.64, 28.74, 28.87, 28.96, 29.00, 30.49, 30.62, 31.24 (14×CH2), 60.96, 61.03 (NCH2), 115.72, 115.94, 116.15, 126.13, 127.11, 129.34, 129.43, 129.72, 129.81, 130.21, 130.24, 145.07, 145.69, 147.32, 149.37, 149.65 (Ar–C), 158.71, 162.29, 164.76, 165.18 (C=N, C=O). 31P NMR (162 MHz, DMSO-d6): δP = − 152.97 to − 135.41 (m, 1P, PF6). 19F NMR (377 MHz, DMSO-d6): δF = − 69.26 (d, 6F, PF6), (− 109.97 to − 109.89), (− 109.45 to − 109.37) (2m, 1F, Ar–F). MS (ES) m/z = 613.30 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-hexadecylpyridin-1-ium tetrafluoroborate (
29
)
It was obtained as yellow syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.83–0.87 (m, 3H, CH3), 1.23–1.30 (m, 26H, 13×CH2), 1.94–2.00 (m, 2H, NCH2CH2), 4.70 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.24 (dd, 0.5H, J = 8 Hz, 12 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.62 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.51 (s, 0.75H, H–C=N), 8.53 (d, 1.5H, J = 4 Hz, Ar–H), 9.25 (d, 0.5H, J = 4 Hz, Ar–H), 9.34 (d, 1.5H, J = 4 Hz, Ar–H), 12.45 (s, 0.75H, CONH), 12.49 (s, 0.25H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.36, 28.34, 28.65, 28.75, 28.87, 28.96, 29.00, 30.49, 30.63, 31.24 (14×CH2), 60.96, 61.03 (NCH2), 115.72, 115.93, 116.15, 126.13, 127.11, 129.35, 129.43, 129.72, 129.80, 130.04, 130.21, 130.24, 145.07, 145.69, 147.30, 149.37, 149.64 (Ar–C), 158.71, 162.28, 164.76, 165.17 (C=N, C=O). 11B NMR (128 MHz, DMSO-d6): δB = − 1.29 to − 1.28 (m, 1B, BF4). 19F NMR (377 MHz, DMSO-d6): δF = (− 109.97 to − 109.90), (− 109.46 to − 109.38) (2m, 1F, Ar–F); − 148.36, − 148.31 (2d, 4F, BF4). MS (ES) m/z = 555.35 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-hexadecylpyridin-1-ium trifluoroacetate (
30
)
It was obtained as colorless syrup. 1H NMR (400 MHz, DMSO-d6): δH = 0.85 (t, 3H, J = 8 Hz, CH3), 1.23–1.30 (m, 26H, 13×CH2), 1.96–1.98 (m, 2H, NCH2CH2), 4.69 (dd, 2H, J = 4 Hz, 8 Hz, NCH2), 7.22 (t, 0.5H, J = 8 Hz, Ar–H), 7.34 (t, 1.5H, J = 8 Hz, Ar–H), 7.61 (dd, 0.5H, J = 4 Hz, 8 Hz, Ar–H), 7.88 (dd, 1.5H, J = 4 Hz, 8 Hz, Ar–H), 8.16 (s, 0.25H, H–C=N), 8.39 (d, 0.5H, J = 4 Hz, Ar–H), 8.52 (s, 0.75H, H–C=N), 8.54 (d, 1.5H, J = 8 Hz, Ar–H), 9.25 (d, 0.5H, J = 8 Hz, Ar–H), 9.33 (d, 1.5H, J = 8 Hz, Ar–H), 12.50 (s, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): δC = 13.88 (CH3), 22.03, 25.35, 28.33, 28.64, 28.73, 28.86, 28.95, 29.00, 30.49, 30.62, 31.23 (14×CH2), 60.95, 61.02 (NCH2), 115.72, 115.94, 116.16, 126.14, 127.11, 129.33, 129.42, 129.71, 129.80, 130.08, 130.26, 145.08, 145.68, 147.33, 149.39 (Ar–C), 158.73, 162.29, 164.76, 165.19 (C=N, C=O). 19F NMR (377 MHz, DMSO-d6): δF = − 73.52 (s, 3F, CF3), (− 109.96 to − 109.88), (− 109.46 to − 109.38) (2m, 1F, Ar–F). MS (ES) m/z = 581.30 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-octadecylpyridin-1-ium hexafluorophosphate (
31
)
It was obtained as yellow syrup. 1H NMR (400 MHz, CDCl3): δH = 0.82 (dd, 3H, J = 4 Hz, 8 Hz, CH3), 1.15–1.18 (m, 30H, 15×CH2), 1.94–1.98 (m, 2H, NCH2CH2), 4.72 (t, 2H, J = 8 Hz, NCH2), 6.95 (t, 2H, J = 8 Hz, Ar–H), 7.67 (dd, 2H, J = 4 Hz, 8 Hz, Ar–H), 8.82 (d, 2H, J = 4 Hz, Ar–H), 9.01 (s, 1H, H–C=N), 9.08 (d, 2H, J = 8 Hz, Ar–H), 12.14 (bs, 1H, CONH). 13C NMR (100 MHz, CDCl3): δC = 14.08 (CH3), 22.66, 26.09, 28.97, 29.33, 29.49, 29.59, 29.64, 29.68, 31.64, 31.90 (16×CH2), 62.69 (NCH2), 115.87, 116.09, 127.71, 129.45, 130.09, 130.18, 144.87, 147.76, 151.75 (Ar–C), 158.62, 163.23, 165.74 (C=N, C=O). 31P NMR (162 MHz, CDCl3): δP = − 153.38 to − 135.76 (m, 1P, PF6). 19F NMR (377 MHz, CDCl3): δF = − 70.39 (d, 6F, PF6), (− 107.98 to − 107.89), (− 107.72 to − 107.65) (2m, 1F, Ar–F). MS (ES) m/z = 641.55 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-octadecylpyridin-1-ium tetrafluoroborate (
32
)
It was obtained as yellow syrup. 1H NMR (400 MHz, CDCl3): δH = 0.82 (dd, 3H, J = 4 Hz, 8 Hz, CH3), 1.16–1.20 (m, 30H, 15×CH2), 1.94–1.98 (m, 2H, NCH2CH2), 4.73 (t, 2H, J = 8 Hz, NCH2), 6.99 (dd, 2H, J = 8 Hz, 12 Hz, Ar–H), 7.69 (dd, 2H, J = 4 Hz, 8 Hz, Ar–H), 8.83 (d, 2H, J = 8 Hz, Ar–H), 9.00 (s, 1H, H–C=N), 9.06 (d, 2H, J = 4 Hz, Ar–H), 12.11 (bs, 1H, CONH). 13C NMR (100 MHz, CDCl3): δC = 14.08 (CH3), 22.66, 26.10, 28.97, 29.33, 29.48, 29.57, 29.63, 29.68, 31.66, 31.90 (16×CH2), 62.64 (NCH2), 115.85, 116.07, 127.76, 129.46, 130.12, 130.21, 144.82, 147.96, 151.72 (Ar–C), 158.57, 163.25, 165.76 (C=N, C=O). 11B NMR (128 MHz, CDCl3): δB = − 1.29 to 1.28 (m, 1B, BF4). 19F NMR (377 MHz, CDCl3): δF = (− 107.98 to − 107.85) to (107.82 to − 107.75) (2m, 1F, Ar–F); − 149.14, 149.19 (2d, 4F, BF4). MS (ES) m/z = 583.45 [M+].
4-(2-(4-Fluorobenzylidene)hydrazinecarbonyl)-1-octadecylpyridin-1-ium trifluoroacetate (
33
)
It was obtained as colorless syrup. 1H NMR (400 MHz, CDCl3): δH = 0.82 (dd, 3H, J = 4 Hz, 8 Hz, CH3), 1.16–1.19 (m, 30H, 15×CH2), 1.95–1.99 (m, 2H, NCH2CH2), 4.75 (t, 2H, J = 8 Hz, NCH2), 6.96 (t, 2H, J = 8 Hz, Ar–H), 7.68 (dd, 2H, J = 4 Hz, 8 Hz, Ar–H), 8.84 (d, 2H, J = 8 Hz, Ar–H), 8.94 (s, 1H, H–C=N), 9.12 (d, 2H, J = 4 Hz, Ar–H), 12.46 (bs, 1H, CONH). 13C NMR (100 MHz, CDCl3): δC = 14.07 (CH3), 22.66, 26.09, 28.96, 29.33, 29.47, 29.57, 29.63, 29.68, 31.66, 31.90 (16×CH2), 62.66 (NCH2), 115.85, 116.07, 127.72, 129.53, 130.09, 130.17, 144.87, 148.01, 151.77 (Ar–C), 158.62, 163.22, 165.73 (C=N, C=O). 19F NMR (377 MHz, CDCl3): δF = − 75.30 (s, 3F, CF3), (− 108.01 to − 107.94), (− 107.85 to − 107.78) (2m, 1F, Ar–F). MS (ES) m/z = 609.35 [M+].
Biological studies
Antiproliferative activity
MCF-7, T47D, HeLa and Caco-II cell lines were cultivated in Dulbecco’s modified Eagles medium (DMEM, Biochrom, Berlin, Germany). Cell lines were maintained at 37 °C and all media were supplemented with 1% of 2 mM l-glutamine (Lonza), 10% fetal calf serum (Gibco, Paisley, UK), 50 IU/ml penicillin/streptomycin (Sigma, St. Louis, MO) and amphotericin B (Sigma, St. Louis, MO). Cells from passage number 10–16 were used. For the antiproliferative activity test, compounds under examination, dissolved in DMSO, were added to the culture medium and incubated for 48 h incubation period in an atmosphere of 5% CO2 and 95 relative humidity at 37 °C.
Cells were seeded at a density of 8 × 103 cells per well in 96-well plates in appropriate medium. When the exposure period ends, Promega Cell Titer 96 Aqueous Non-Radioactive Cell Proliferation (MTS) assay was carried out according to the manufacturer’s protocol. Absorbance values of each well were determined with a microplate enzyme-linked immuno-assay (ELISA) reader equipped with a 492 nm filter. Survival rates of the controls were set to represent 100% viability. Untreated cultures were used as controls groups.
Caspase-3 enzyme activity
To assess changes in caspase-3 activity, the caspase-3 colorimetric assay kit (BioVision Research Products, Milpitas, CA) was used after treatment with 100 µM of each compound and incubation for 48 h. Briefly, apoptosis was provoked in treated cells before cells were collected by centrifugation at 1000 rpm for 10 min. Cells were lysed and supernatants were separated according to the manufacture’s protocol. Protein concentration in the supernatant was determined using the Bradford method. 50 µl of the reaction buffer, 200 µM of DEVD-pNA substrate were added to 50 µl supernatant in a 96-well plate and incubated at 37 °C for 2 h. After incubation, the plate was read under 405 nm wavelength using an ELISA reader (Tecan Group Ltd., Mannedorf, Switzerland).
Computational methods
Preparation of protein structure
The crystal structure of apo PI3Kα (PDB ID: 2RD0) [(2)] was retrieved from the RCSB Protein Data Bank. The homology modeled structure of 2RD0 was adopted for this study [47]. The coordinates of wortmannin in 3HHM [48] were moved to 2RD0 and assigned as the ligand. Minimization of the protein side chains was applied to reduce the steric clashes recruiting MacroModel [20] module in MAESTRO. Further preparation of the coordinates was carried out using Protein Preparation [20] wizard in Schrödinger to maximize the H-bond interactions between residues.
Preparation of ligand structures
The synthesized compounds (ligands) were built based on the coordinates of wortmannin in 3 HHM. The ligands were built using MAESTRO [20] BUILD module and then subjected for energy minimization using OPLS2005 force field in MacroModel program.
Quantum–polarized ligand docking (QPLD)
QPLD [20, 45] (3, 4) docking employed the combined QM/MM approach to determine ligand/protein complex formation. The Glide [49,50,51] docking was implemented in QPLD to generate a list of ligand docked poses that fit the protein binding site. The binding energy of the protein/newly generated ligand pose was derived using the molecular mechanical (MM) method for the protein coordinates while the quantum mechanical (QM) method was applied for ligand pose recruiting the QSite wizard in Schrödinger [45]. The Qsite program generated the atomic partial charges for the ligand pose within the protein environment. The ligand pose with QM-generated partial charges were redocked to the binding pocket using Glide [45] program with XP-scoring function. Specifically, the polarization effect of the protein binding pocket was accounted during the docking procedure. The ligand pose with the lowest root mean square deviation (RMSD) was investigated. The kinase binding domain was defined using the ligand as a centroid. The scaling of receptor Vander Waals for the non-polar atoms was set to 0.75.