Materials and methods
The solvents used were of HPLC reagent grade. The commercial isophthalic acid (Merck), pyridine-2,6-dicarboxylic acid (Aldrich), pyridine-3,5-dicarboxylic acid (Aldrich), Fmoc-amino acids namely Fmoc-Ala-OH 1, Fmoc-Val-OH 2, and (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) (HATU) (IRIS Biotech, Germany), benzidine (Aldrich) 3, 4,4′-oxydianiline (Aldrich) 4 and the solvents triethylamine (Et3N), N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), 1-Methyl-2-pyrrolidone (NMP) (Fluka), diethylamine, acetonitrile, chloroform, n-hexane, ethyl alcohol were used as purchased without purification.
Melting points were determined with a Mel-Temp apparatus and are uncorrected. Infrared spectra (IR) were recorded on a FTIR-8400S Shimadzu-Japan or on a Perkin-Elmer 1600 series, Fourier transform instrument as KBr pellets. Absorption spectra were measured with a UV 500 UV–vis spectrometer at room temperature (rt) in DMSO with a polymer concentration of 1 mg/10 mL. Magnetic resonance spectra (1H NMR and 13C NMR spectra) were recorded on a JEOL 500 MHz spectrometer with chemical shift values reported in δ units (ppm) relative to an internal standard. Follow-up of the reactions and checks of the purity of the compounds was done by thin layer chromatography (TLC) on silica gel-protected aluminum sheets (Type 60 GF254, Merck) and the spots were detected by exposure to UV-lamp at λ 254 nm for a few seconds. Differential thermogravimetric (DTG) analyses were carried out in the temperature range from 20°C to 500°C in a steam of nitrogen atmosphere by Shimadzu DTG 60H thermal analyzer. The experimental conditions were: platinum crucible, nitrogen atmosphere with a 30 ml/min flow rate and a heating rate 10°C/min. Differential thermal analysis (TGA/DTA) analyses were carried out using SDT-Q600-V20.5-Build at the Institute of Graduate Studies and Research, Alexandria University and at the Microanalysis Center, Cairo University, Giza, Egypt. Elemental analyses were performed at the Microanalytical Unit, Cairo University and Center for mycology and biotechnology, Alazhar University, Cairo.
Synthesis of Bis Fmoc-protected diamines 5–8 (general method)
To a solution of Fmoc–Ala-OH 1 (0.623 g, 2 mmol) or Fmoc–Val-OH 2 (0.679 g, 2 mmol); diisopropylethylamine (DIEA, 0.7 mL, 4 mmol) in 5 mL DMF was added HATU (0.76 g, 2 mmol) as a coupling reagent. The reaction mixture was stirred for 3 min (to preactivate the carboxylic acid and form the N-protect amino acid active ester), followed by the addition of a solution of diamine 3 (0.2 g, 1 mmol) or 4 (0.184 g, 1 mmol) in 2 ml DMF. The reaction mixture was stirred overnight and then was poured over water. The precipitate was filtered, washed with 5% citric acid (3 × 20 mL), saturated NaHCO3 (3 × 20 mL) and water. The crude product was recrystallized from CH2Cl2/hexane.
Bis((9H-fluoren-9-yl)methyl) 1,1′-(biphenyl-4,4′-diylbis(azanediyl))bis(1-oxopropane-2,1-diyl)dicarbamate 5 (FT-IR, 1H NMR and 13C NMR are attached as supporting information; Additional files 1, 2, 3respectively)
The reaction of Fmoc-Ala-OH 1 with benzidine 3 gave compound 5. The product was obtained as a white powder, mp 158-159°C, in yield 0.65 g (84%). IR (KBr): 3301 (NH), 1671 (C=O, amide) cm-1. 1H-NMR (CDCl3, 500Hz): δ 1.23-1.30 (m, 6H, 2 CH3), 4.18-4.24 (m, 4H, 4 CH), 6.24 (s, 4H, 2 CH2), 6.82, 6.92 (2brs, 2H, 2 NH, D2O exchangeable), 7.31-7.86 (m, 24H, Ar-H), 10.11, 10.13 (2s, 2H, 2 NH, D2O exchangeable). 13C-NMR (CDCl3, 125Hz): δ 21.82, 51.41, 110.34, 120.16, 120.54, 121.90, 126.95, 127.90, 129.53, 134.99, 137.88, 138.39, 139.87, 143.00, 154.00, 175.60. Anal. Calcd for C48H42N4O6: C, 74.79; H, 5.49; N, 7.27. Found: C, 75.02; H, 5.77; N, 6.95.
Bis((9H-fluoren-9-yl)methyl)-1,1′-(biphenyl-4,4′-diylbis(azanediyl))bis(3-methyl-1-oxobutane-2,1-diyl) dicarbamate 6 (FT-IR, 1H NMR and 13C NMR are attached as supporting information; Additional files 4, 5, 6respectively)
The reaction of Fmoc-Val-OH 2 with benzidine 3 gave compound 6. The product was obtained as a white powder, mp 212-213°C, in yield 0.77 g (93%). IR (KBr): 3289 (NH), 1692, 1660 (C=O, amide) cm-1. 1H-NMR (CDCl3, 500Hz): δ 0.82, 0.89 (2d, 12H, J= 6.9 Hz, 4 CH3), 1.86-1.90 (m, 2H, 2 CH), 3.08 (d, 2H, J = 6.1 Hz, 2 CH), 3.77-3.81 (m, 2H, 2 CH), 6.24 (s, 4H, 2 CH2), 7.30, 7.38 (2t, 8H, J = 7.6 Hz, Ar-H), 7.51-7.56 (m, 5H, NH+ Ar-H), 7.64-7.69 (m, 5H, NH+ Ar-H), 7.80, 7.84 (2d, 8H, J = 7.6 Hz, Ar-H), 9.95, 10.45 (2brs, 2H, 2 NH, D2O exchangeable). 13C-NMR (CDCl3, 125Hz): δ 17.84, 18.99, 19.94, 20.02, 20.15, 61.33, 110.34, 120.08, 120.57, 121.93, 126.96, 127.84, 129.47, 137.94, 139.93, 143.08, 174.50. Anal. Calcd for C52H50N4O6: C, 75.52; H, 6.09; N, 6.77. Found: C, 75.36; H, 5.95; N, 6.51.
Bis((9H-fluoren-9-yl)methyl)-1,1′-(4,4′-oxybis(4,1-phenylene)bis(azanediyl))bis(1-oxopropane-2,1-diyl)dicarbamate 7 (FT-IR, 1H NMR and 13C NMR are attached as supporting information; Additional files 7, 8, 9respectively)
The reaction of Fmoc-Ala-OH 1 with 4,4′-oxydianiline 4 gave compound 7. The product was obtained as a white powder, mp 133-134°C, in yield 0.66 g (84%). IR (KBr): 3452, 3288 (NH), 1668 (C=O, amide) cm-1. 1H-NMR (CDCl3, 500Hz): δ 1.27 (d, 6H, 2 CH3), 4.18-4.24 (m, 8H, 4 CH+ 2 CH2), 6.90 (d, 4H, Ar-H), 7.27-7.32 (m, 4H, Ar-H), 7.38 (t, 4H, Ar-H), 7.56 (d, 4H, Ar-H), 7.65 (d, 1H, NH, D2O exchangeable), 7.71 (t, 4H, Ar-H), 7.80 (d, 1H, NH, D2O exchangeable), 7.85 (d, 4H, Ar-H), 9.99 (s, 2H, 2 NH, D2O exchangeable). 13C-NMR (CDCl3, 125Hz): δ 21.66, 51.17, 110.31, 119.22, 120.50, 121.67, 121.87, 127.94, 129.57, 134.63, 137.83, 139.82, 142.93, 153.15, 175.46. Anal. Calcd for C48H42N4O7: C, 73.27; H, 5.38; N, 7.12. Found: C, 73.64; H, 5.09; N, 6.87.
Bis((9H-fluoren-9-yl)methyl)-1,1′-(4,4′-oxybis(4,1-phenylene)bis(azanediyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate 8 (FT-IR, 1H NMR and 13C NMR are attached as supporting information; Additional files 10, 11, 12respectively)
The reaction of Fmoc-Val-OH 2 with 4,4′-oxydianiline 4 gave compound 8. The product was obtained as a white powder, mp 193-194°C, in yield 0.75 g (89%). IR (KBr): 3292 (NH), 1691, 1660 (C=O, amide) cm-1. 1H-NMR (CDCl3, 500Hz): δ 0.80, 0.87 (2d, 12H, J= 6.9 Hz, 4 CH3), 1.84-1.90 (m, 2H, 2 CH), 3.04 (d, 2H, J = 5.4 Hz, 2 CH), 6.24 (s, 4H, 2 CH2), 6.90 (d, 4H, J= 8.4 Hz, Ar-H), 7.30, 7.38 (2t, 8H, J= 7.6 Hz, Ar-H), 7.50-7.58 (m, 2H, 2 NH, D2O exchangeable), 7.60 (d, 4H, J= 8.4 Hz, Ar-H), 7.80, 7.84 (2d, 8H, J= 7.6 Hz, Ar-H), 9.83, 10.47 (2brs, 2H, 2 NH, D2O exchangeable). 13C-NMR (CDCl3, 125Hz): δ 17.85, 20.16, 31.10, 61.27, 110.36, 119.18, 120.57, 121.34, 121.93, 127.83, 129.46, 134.98, 137.94, 139.94, 143.08, 152.99, 174.29. Anal. Calcd for C52H50N4O7: C, 74.09; H, 5.98; N, 6.65. Found: C, 73.87; H, 5.53; N, 6.21.
General procedure for the deblocking of the Fmoc-protecting groups: preparation of the diamines 9–12
Protected diamine (0.5 mmol) 5–8 was stirred with 40 ml (30% Et2NH / CH3CN) at r.t. for 14h. The progress of the reaction was monitored by using TLC using ethyl acetate / hexane 4:6 v/v as eluent. The solvent and volatiles were removed under reduced pressure and the crude residue was washed thoroughly with hexane to get rid from the deblocked dibenzofulvene byproduct to produce the desired diamine 9–12 which is used directly to the next step.
Preparation of polymers 16–25 by low-temperature solution polycondensation (general method)
To a mechanically stirred cold (ice bath) solution of the diamine 9–12 (1.0 mmol) dissolved in 5.0 mL DMA, a solution of 1.0 mmol of the acid dichloride 13, 14, 15 dissolved in 5.0 mL DMA was added dropwise. The reaction mixture was allowed to stir for 2h then the mixture was poured into iced water. The formed polymer precipitate was filtered under vacuum, washed thoroughly with water, ethyl alcohol and water again, dried and kept in the desiccator.
Poly[3-acetyl-N-((2S)-1-(4′-(2-(methylamino)propanamido)biphenyl-4-ylamino)-1-oxopropan-2-yl)benzamide] 16
The polymerization of the diamine 9 with isophthaloyl dichloride 13 produced the polymer 16 as a black solid, yield 59.0%, m. p. > 300°C, UV (DMSO): λmax= 272 nm (ε =1569), λmax= 304 nm (ε =1684), IR (cm-1): 3230 (N-H, amide), 3064 (=C–H, aromatic), 2921 (C–H, aliphatic), 1658 (C=O, amide), 1599 and 1497 (C=C, aromatic), 1114 and 1071 (C–N, aliphatic). Calculated for C26H26N4O5; C, 65.81; H, 5.52; N, 11.81; Found: C, 65.52; H, 5.78; N, 11.55.
Poly[3-acetyl-N-((2S)-3-methyl-1-(4′-(3-methyl-2-(methylamino) butanamido)biphenyl-4-ylamino)-1-oxobutan-2-yl)benzamide] 17
The polymerization of the diamine 10 with isophthaloyl dichloride 13 produced the polymer 17 as a black solid, yield 56.0%, m. p. > 300°C, UV (DMSO): λmax= 275 nm (ε =2244), λmax= 300 nm (ε =2156), IR (cm-1): 3430 (N-H, amide), 3039 (=C–H, aromatic), 2921 (C–H, aliphatic), 1658 (C=O, amide), 1607 and 1446 (C=C, aromatic), 1249 and 1113 (C–N, aliphatic). Calculated for C30H34N4O5; C, 67.91; H, 6.46; N, 10.56; Found: C, 67.72; H, 6.70; N, 10.77.
Poly[3-acetyl-N-((2S)-1-(4-(4-(2-(methylamino)propanamido)phenoxy) phenylamino)-1-oxopropan-2-yl)benzamide] 18
The polymerization of the diamine 11 with isophthaloyl dichloride 13 produced the polymer 18 as a black solid, yield 68.0%, m. p. > 300°C, UV (DMSO): λmax= 268 nm (ε =1359), λmax= 276 nm (ε =1169), λmax= 362 nm (ε = 86), IR (cm-1): 3439 (N-H, amide), 3096 (=C–H, aromatic), 2935 (C–H, aliphatic), 1669 (C=O, amide), 1592 and 1490 (C=C, aromatic), 1114 and 1070 (C–N , aliphatic). Calculated for C26H26N4O6; C, 63.66; H, 5.34; N, 11.42; Found: C, 63.29; H, 5.08; N, 11.73.
Poly[3-acetyl-N-((2S)-3-methyl-1-(4-(4-(3-methyl-2-(methylamino)butanamido) phenoxy)phenylamino)-1-oxobutan-2-yl)benzamide] 19
The polymerization of the diamine 12 with isophthaloyl dichloride 13 produced the polymer 19 as a black solid, yield 60.0%, m. p. > 300°C, UV (DMSO): λmax= 268 nm (ε =1754), λmax= 330 nm (ε =158), IR (cm-1): 3477 (N-H, amide), 3036 (=C–H, aromatic), 2887 (C–H, aliphatic), 1640 (C=O, amide), 1610 and 1475 (C=C, aromatic), 1216 and 1150 (C–N, aliphatic). Calculated for C30H34N4O6; C, 65.92; H, 6.27; N, 10.25; Found: C, 66.28; H, 6.61; N, 10.60.
Poly[6-acetyl-N-((2S)-1-(4′-(2-(methylamino)propanamido)biphenyl-4-ylamino)-1-oxo propan-2-yl)picolinamide] 20
The polymerization of the diamine 9 with pyridine-2,6-dicarbonyl dichloride 14 produced the polymer 20 as a black solid, yield 56.0%, m. p. > 300°C, UV (DMSO): λmax= 268 nm (ε =1930), λmax= 321 nm (ε =459), IR (cm-1): 3400 (N-H, amide), 3063 (=C–H, aromatic), 2934 (C–H, aliphatic), 1668 (C=O, amide), 1590 and 1489 (C=C, aromatic), 1440 (C–N , aromatic), 1113 and 1070 (C–N, aliphatic). Calculated for C25H25N5O5; C, 63.15; H, 5.30; N, 14.73; Found: C, 63.41; H, 5.06; N, 14.61.
Poly[6-acetyl-N-((2S)-3-methyl-1-(4′-(3-methyl-2-(methylamino) butanamido)biphenyl-4-ylamino)-1-oxobutan-2-yl)picolinamide] 21
The polymerization of the diamine 10 with pyridine-2,6-dicarbonyl dichloride 14 produced the polymer 21 as a black solid, yield 62.0%, m. p. > 300°C, UV (DMSO): λmax= 275 nm (ε = 2162), λmax= 299 nm (ε =2106), IR (cm-1): 3416 (N-H, amide), 3039 (=C–H, aromatic), 2890 (C–H, aliphatic), 1642 (C=O, amide), 1613 and 1477 (C=C, aromatic), 1445 (C–N , aromatic), 1215 and 1150 (C–N , aliphatic). Calculated for C29H33N5O5; C, 65.52; H, 6.26; N, 13.17 Found: C, 65.85; H, 5.96; N, 12.89.
Poly[6-acetyl-N-((2S)-1-(4-(4-(2-(methylamino)propanamido)phenoxy) phenylamino)-1-oxopropan-2-yl)picolinamide] 22
The polymerization of the diamine 11 with pyridine-2,6-dicarbonyl dichloride 14 produced the polymer 22 as a black solid, yield 58.0%, m. p. > 300°C, UV (DMSO): λmax= 268 nm (ε = 767), λmax= 276 nm (ε =651), IR (cm-1): 3440 (N-H, amide), 3096 (=C–H, aromatic), 2936 (C–H, aliphatic), 1692 (C=O, amide), 1591 and 1490 (C=C, aromatic), 1441 (C–N , aromatic), 1113 and 1070 (C–N , aliphatic). Calculated for C25H25N5O6; C, 61.09; H, 5.13; N, 14.25 Found: C, 61.32; H, 5.44; N, 13.98.
Poly[5-acetyl-N-((2S)-1-(4′-(2-(methylamino)propanamido)biphenyl-4-ylamino)-1-oxopropan-2-yl)nicotinamide] 23
The polymerization of the diamine 9 with pyridine-3,5-dicarbonyl dichloride 15 produced the polymer 23 as a black solid, yield 67.0%, m. p. > 300°C, UV (DMSO): λmax= 268 nm (ε =957), λmax= 276 nm (ε =860), λmax= 322 nm (ε =179), IR (cm-1): 3416 (N-H, amide), 3087 (=C–H, aromatic), 2936 (C–H, aliphatic), 1669 (C=O, amide), 1593 and 1490 (C=C, aromatic), 1441 (C–N , aromatic), 1113 and 1070 (C–N, aliphatic). Calculated for C25H25N5O5; C, 63.15; H, 5.30; N, 14.73; Found: C, 63.33; H, 5.66; N, 14.99.
Poly[5-acetyl-N-((2S)-3-methyl-1-(4′-(3-methyl-2-(methylamino) butanamido)biphenyl-4-ylamino)-1-oxobutan-2-yl)nicotinamide] 24
The polymerization of the diamine 10 with pyridine-3,5-dicarbonyl dichloride 15 produced the polymer 24 as a black solid, yield 58.0%, m. p. > 300°C, UV (DMSO): λmax= 269 nm (ε =888), λmax= 276 nm (ε =731), IR (cm-1): 3420 (N-H, amide), 3036 (=C–H, aromatic), 2881 (C–H, aliphatic), 1639 (C=O, amide), 1612 and 1475 (C=C, aromatic), 1444 (C–N , aromatic), 1215 and 1150 (C–N , aliphatic). Calculated for C29H33N5O5; C, 65.52; H, 6.26; N, 13.17 Found: C, 65.17; H, 6.54; N, 13.51.
Poly[5-acetyl-N-((2S)-1-(4-(4-(2-(methylamino)propanamido)phenoxy) phenylamino)-1-oxopropan-2-yl)nicotinamide] 25
The polymerization of the diamine 11 with pyridine-3,5-dicarbonyl dichloride 15 produced the polymer 25 as a black solid, yield 54.0%, m. p. > 300°C, UV (DMSO): λmax= 269 nm (ε =1871), λmax= 367 nm (ε =166), IR (cm-1): 3440 (N-H, amide), 3085 (=C–H, aromatic), 2934 (C–H, aliphatic), 1668 (C=O, amide), 1591 and 1489 (C=C, aromatic), 1440 (C–N , aromatic), 1113 and 1070 (C–N , aliphatic). Calculated for C25H25N5O6; C, 61.09; H, 5.13; N, 14.25 Found: C, 60.98; H, 4.96; N, 14.63.