Synthesis and physical behavior ofamphiphilicdendrimerswith layered organization of hydrophilic and hydrophobic blocks

Ignaty Leshchiner*1, Natalia Boiko1, Jayant Kumar2, Robert M.Richardson4, Aziz Muzafarov3 and Valery Shibaev1

1Chemistry Department, MoscowStateUniversity, Leninskie gory, Moscow, 119991 Russia

2 Center for Advanced Materials,University of Massachusetts, Lowell, Massachusetts, 01854

3 Institute of Synthetic Polymeric Materials of theRussianAcademy of Sciences,117393 Moscow, Russia

4H.H. Wills Physics Laboratory,University of Bristol, Bristol BS8 1TL, UK

*corresponding author:

Supporting information

Table of Contents

1. Syntheticprocedures:Fragments for dendrimers with hydrophilic periphery.…...... ….S1

2. Synthetic procedures: Dendrimers…………………….…..………………….……...…S3

3.1H,13C 1D and 2D NMR spectra for the silane end group and selected dendrimers….S5

4. GPC and MALDI-TOF MS data for selected compounds………….……….….....…..S9

5. DSC and POM data for selectedamphiphilic dendrimers….…………….……………S11

6. Brewster angle microscopy and Langmuir measurements……………………………..S12

1. Synthetic procedures:

Fragments for dendrimers with hydrophilic periphery

2-[2-(2-ethoxyethoxy)ethoxy]ethyl 4-[(methoxycarbonyl)oxy]benzoate (P-x1)

Tothesolution of monoethyltetraethyleneglycol 3,88 ml (22,2 mmol) and NEt3 (3,1 ml, 22,2 mmol) in dry THF (30ml) the solution of compound I in dry THF was slowly added (4,76 g, 22,2 mmol).The resulting mixture was further stirred for 6 hrs without cooling, and then filtered and evaporated under vacuum. Theresiduewasdissolvedindiethylether (300ml), washed 3 times with water, dried over anhydrous sodium sulfateand evaporated under reduced pressure. Receivedviscousliquid was purified by column chromatography, eluent hexane-ethylacetate 2:1.Yield 5,295 g (67,6%) of colorless oil. NMR1Н (500 MHz, CDCl3, ppm): 1.20 (t, 3H, J= 6.9 Hz), 3.52 (q, 2H, J1= 7.0 Hz, J2= 20.9 Hz), 3.58 (t, 2H, J= 5.4 Hz), 3.63-3.75 (m, 6H), 3.83 (t, 2H, J=5.0 Hz), 3.92 (s, 3H), 4.48 (t, 2H, J=4.7 Hz), 7.26 (d, 2H, J=8.8 Hz), 8.10 (d, 2H, J=8.8 Hz).

2-[2-(2-ethoxyethoxy)ethoxy]ethyl 4-hydroxybenzoate (P-x2)

TothesolutionofcompoundP-x1 (5,06 g, 14,2 mmol) in 10 mlof the mixture ethanol-THF (1:1) 25 ml 25% aqueous ammonia solution was added dropwise. Thereactionmiхturewas stirred at room temperature for another 2 hrs. After that the reaction mixture was poured into water and the pH was adjusted to 8 with 1N HCl.The resulting suspension was extracted with diethylether three times. Combineddiethyletherfractions were washed with water once and then dried overanhydrous sodium sulfate.The resulting solution was evaporated till dryness in vacuo.Yield 4,197 (98,9%). NMR1Н (500 MHz, CDCl3, ppm): 1.18 (t, 3H, J= 7.0 Hz), 3.51 (q, 2H, J1= 7.0 Hz, J2= 21.1 Hz), 3.58 (t, 2H, J= 4.7 Hz), 3.63-3.74 (m, 6H), 3.82 (t, 2H, J=4.7 Hz), 4.43 (t, 2H, J=4.7 Hz), 6.83 (d, 2H, J=8.8 Hz), 7.86 (d, 2H, J=8.8 Hz).

4-(2,5,8,11-tetraoxatridecan-1-oyl)phenyl 4-(undec-10-en-1-yloxy)benzoate (P-x3)

To a cooled solution of compoundP-x2 (4,17 g, 14,0 mmol), 4-(undec-10-en-1-yloxy) benzoic acid (4,06 g, 14,0 mmol) and 0,17 g (1,4 mmol) dimethylaminopyridine in dry THF3,75 g (18,2 mmol) DCC (dicyclocarbodiimide) was added. Thereactionmixturewasstirredfor 24 hrs, filtered and dried in vacuum. Theresiduewasdissolvedindiethylether (300ml), washed with water three times, dried overanhydrous sodium sulfate and evaporated in vacuum.Thereceived oil was purified with column chromatography over silica gel, eluent petroleum ether:ethylacetate 2:1. Yield5,51 g (69%). NMR1Н (300 MHz, DMSO-d6, ppm): 1.06 (t, 3H, J= 6.9 Hz), 1.17-1.55 (m, 12H), 1.72 (m, 2H), 1.99 (m, 2H), 3.36-3.63 (m, 10H), 3.75 (t, 2H, J=4.5 Hz), 4.07 (t, 2H, J=6.4 Hz), 4.40 (t, 2H, J=4.4 Hz), 4.92 (d, 1H), 4.98 (d, 1H), ), 5.77 (m, 1H), 7.10 (d, 2H, J=8.8 Hz), 7.43 (d, 2H, J=8.7 Hz), 8.06 (m, 4H).

4-(2,5,8,11-tetraoxatridecan-1-oyl)phenyl 4-{[11-(1,1,3,3-tetramethyldisiloxanyl)undecyl]oxy}benzoate(P-x4)

TothesolutionofcompoundP-x3(5,345 g, 9,4 mmol) andchlorodimethylsilane (5,19 ml, 46,8 mmol) in absolute toluene (4 ml) 20l of the Pt-catalyst (PC-072divinyltetramethyldislixane platinum complex in xelene) was added. The resulted solution was stirred under argon for a week. The reaction was monitored 1НNMR until the extinction of thesignals corresponding to the proton signals of the end double bond: =5.15 (m, 2Н) и=5.91 (m,1Н). Tothereactionmixture 36,33 ml (0.33 mol) ofadditionalhlorodimethylsilanein 30 ml of dry THFwas addedand at 0Сthe solution of 23 ml (0.28 mol) pyridineand 6,74 ml (0.37 mol) of waterin 30 mlof THF was added dropwise. Thereactionmixturewasstirredatrtfor 30 min, after which 300 ml of chloroform and 50 ml of water was added.The chloroform layer was washed with water three times until a neutral pH. Chloroformsolutionwasdriedoveranhydrous sodium sulfateand evaporated under reduced pressure. The resulting compound was purified by column chromatography over silica gel, eluent petroleum ether- ethylacetate 2:1. Yield5,307 g (80,4%) colorless oil. NMR1Н (500 MHz, CDCl3, ppm): 0.05 (s, 6H), 0.16 (d, 6H), 0.52 (m, 2H), 1.20 (t, 3H, J= 7.1 Hz), 1.23-1.40 (m, 12H), 1.47 (m, 2H), 1.72 (m, 2H), 1.88 (m, 2H), 3.51 (q, 2H, J1= 7.3 Hz, J2= 20.8 Hz), 3.58 (t, 2H, J= 6.5 Hz), 3.63-3.74 (m, 6H), 3.84 (t, 2H, J=4.3 Hz), 4.04 (t, 2H, J=6.3 Hz), 4.48 (t, 2H, J=4.4 Hz), 4.67 (m, 1H), 4.98 (d, 1H), ), 5.77 (m, 1H), 6.97 (d, 2H, J=8.4 Hz), 7.28 (d, 2H, J=8.4 Hz), 8.13 (d, 4H, J=8.6 Hz).

2. Synthetic procedures: Dendrimers of third generation

Dendrimers with hydrophobic periphery

DendrimerG-1-(Peg-Benz)

Tothereactionmixturecontaining 50 mg (7,1710-5mol) ofcarbosilanedendriticmatrix G-1(All)8, 0,572 g (8,6104mol) ofcompoundP-y5and 10 mlofabsolutetoluene 10 ulofthePt-catalyst (PC-072divinyltetramethyldisiloxaneplatinumcomplexinxelene) wasadded.Thereactionmixturewasstirredin a closed flask under argon on 35С oil bath for4 days. Thereactionwasmonitoredby1НNMRandGPC. Thereactionmixturewasfilteredthroughashortsilicagelcolumn (eluenttoluene (300ml) and then THF) forthedeactivationofthecatalyst. The final purification of the dendrimer was conducted by semipreparative-GPC.Yield was 173,8 mg (40%) of chromatographically pure dendrimer. MALDI-TOF MS (2,5-hydroxybenzoic acid, [M+Na]+) m/z 6037.85exp. (6038.96theor.).NMR1Н (500 МHz, CD2Cl2, ppm): -0.05 (s, 12Н), 0.05 (s, 48Н), 0.07 (s, 48Н), 0.51 (m, 16Н), 0.59 (m, 48Н), 1.00 (t, 24Н, J= 7.5 Hz), 1.36(m, 24Н), 1.52 (m, 16H), 1.58 (m, 16H), 1.81 (m, 16H), 3.39 (t, 16H, J= 6.9 Hz), 3.54 (m, 16H), 3.56-3.65 (m, 64H), 3.68 (m, 16H), 3.82 (t, 16H, J=4.7 Hz), 4.07 (t, 16H, J=6.5 Hz), 4.47 (t, 16H, J=4.7 Hz), 7.00 (d, 16H, J=8.8 Hz), 7.31 (d, 16H, J=8.5 Hz), 8.12 (m, 32H). NMR13C (125 MHz, CD2Cl2, ppm) -4.81, 0.50, 0.69, 13.97, 14.69, 18.35, 18.97, 19.05, 19.58, 23.62, 23.94, 31.55, 64.71, 68.58, 69.57, 70.44, 70.95, 70.96, 71.01, 71.03, 71.12, 74.50, 114.81, 121.55, 122.28, 128.13, 131.46, 132.64, 155.38, 164.29, 164.66, 166.01.

DendrimerG-3-(Peg-Benz)

ThesynthesiswasconductedinasimilarwayasG-1(Peg-Benz)from 50 mg (1,3410-5mol) carbosilanedendriticmatrix G-3(All)32, 0,428 g (6,44104mol) of compoundP-y5and 10 ul ofРС-072. The final purification of the dendrimer was conducted by semipreparative-GPC. Yield 17 mgofchromatographically pure dendrimer.NMR1Н (CDCl3, 500 МHz, ppm):  -0.05 (s, 84Н); 0.05 (s, 192Н); 0.07 (s, 192Н); 0.51 (m, 64Н); 0.59 (m, 240Н); 1.00 (t, 96Н, J= 7.5 Hz); 1.36(m, 120Н), 1.52 (m, 64H), 1.58 (m, 64H), 1.81 (m, 64H), 3.39 (t, 64H, J= 6.9 Hz), 3.54 (m, 64H), 3.56-3.65 (m, 256H), 3.68 (m, 64H), 3.82 (t, 64H, J=4.7 Hz), 4.07 (t, 64H, J=6.5 Hz), 4.47 (t, 64H, J=4.7 Hz), 7.00 (d, 64H, J=8.8 Hz), 7.31 (d, 64H, J=8.5 Hz), 8.12 (m, 128H).

Dendrimers withhydrophilic periphery

DendrimerG-1(Benz-Peg)

ThesynthesiswasconductedinasimilarwayasG-1(Peg-Benz)from 45 mg (6,4510-5mol)carbosilanedendriticmatrixG-1(All)8, 0,634 g (8,99104mol)of compoundP-x4and 10 ul ofРС-072. The final purification of the dendrimer was conducted by semipreparative-GPC. Yield was70 mg (17%)ofchromatographically pure dendrimer. MALDI-TOF MS (2,5-hydroxybenzoic acid, [M+Na]+) m/z 5654.13exp. (5655.12theor., 7 groups).NMR1Н (500 МHz, CDCl3, ppm): -0.07 (s, 12Н), 0.03 (s, 96Н), 0.49 (m, 16Н), 0.55 (m, 48Н), 1.20 (t, 24H, J= 7.0 Hz), 1.25-1.39 (m, 120H), 1.47 (m, 16H), 1.81(m, 16Н), 3.51 (q, 16H, J1= 7.3 Hz, J2= 20.8 Hz), 3.58 (t, 16H, J= 4.9 Hz), 3.63-3.74 (m, 48H), 3.84 (t, 16H, J=4.3 Hz), 4.03 (t, 16H, J=6.3 Hz), 4.49 (t, 16H, J=4.6 Hz), 6.97 (d, 16H, J=8.5 Hz), 7.28 (d, 16H, J=7.9 Hz), 8.13 (d, 32H, J=7.9 Hz).

DendrimerG-3(Benz-Peg)

ThesynthesiswasconductedinasimilarwayasG-1(Peg-Benz)from 100 mg (2,6810-5mol)carbosilanedendriticmatrixG-3(All)32, 0,911 g (1,29103mol) of compoundP-x4and 10 ul ofРС-072. The final purification of the dendrimer was conducted by semipreparative-GPC. Yield12 mg ofchromatographically pure dendrimer. NMR1Н (500 МHz, CDCl3, ppm): -0.07 (s, 84Н), 0.03 (s, 384Н), 0.49 (m, 64Н), 0.55 (m, 240Н), 1.20 (t, 96H, J= 7.0 Hz), 1.25-1.39 (m, 504H), 1.47 (m, 64H), 1.81(m, 64Н), 3.51 (q, 64H, J1= 7.3 Hz, J2= 20.8 Hz), 3.58 (t, 64H, J= 4.9 Hz), 3.63-3.74 (m, 192H), 3.84 (t, 64H, J=4.3 Hz), 4.03 (t, 64H, J=6.3 Hz), 4.49 (t, 64H, J=4.6 Hz), 6.97 (d, 64H, J=8.5 Hz), 7.28 (d, 64H, J=7.9 Hz), 8.13 (d, 128H, J=7.9 Hz).

3.1H,13C 1D and 2D NMR spectra for the silane end group and selected dendrimers

Figure S1.13C-APT NMRspectra of the All-PegPhOH (P-y3).

Figure S2.13C-APT NMRspectra of the All-PegBenz (P-y4).

Figure S3.COSY (1H, 1H) NMRspectra of the All-PegBenz (P-y4).

Figure S4.COSY (1H, 1H) NMR spectra spectra of of the All-PegBenz (P-y4).

Figure S5.COSY (1H, 1H) NMRspectra of of the silane PegBenz (P-y5).

Figure S6. HSQC (1H, 13C) NMR spectra of of the silane PegBenz (P-y5).13C-APT (ordinate axis), 1H NMR(abscissa axis).

FigureS7.1H NMR spectraof amphphilic dendrimerG-1(Benz-Peg)

Figure S8.COSY (1H, 1H) NMR spectra of first generation amphiphilic dendrimer
G-1(Peg-Benz).

Figure S9. HSQC (1H, 13C) spectra of the first generation amphiphilic dendrimer G­1(Peg­Benz).

4. GPC and MALDI-TOF MS data for selected compounds

Figure S10.GPC curvesof first and third generation amphiphilic dendrimersG-n(Peg-Benz).

Figure S11.GPC curveof third generation amphiphilic dendrimer G-3(Benz-Peg).

Figure S12.MALDI- TOF MS spectra of the silanePegBenz (P-y5) (bottom); model spectra (top).

Figure S13.MALDI-TOF MS spectra of G­1(Peg­Benz)amphiphilic dendrimer.

5. DSC and POM data for selectedamphiphilic dendrimers

Figure S14.DSC scan from dendrimer G-1(Peg-Benz)with inner hydrophilic layer and hydrophobic periphery. Insert shows polarizing optical micrograph of the dendrimer at 20oC (crystalline phase).

Figure S15.DSC scan from dendrimer G-1(Benz-Peg)with inner hydrophilic layer and hydrophobic periphery.Polarizing optical micrograph of the dendrimer at -19oC.

6. Brewster angle microscopy and Langmuir measurements.

a)b)c)d)
e)f)

Figure S16.BAM microphotographs for G-3(Peg-Benz) at a) 2.5 mN/m b) 3 mN/m c) 11.7 mN/m d) 13.6 mN/m e) 16mN/m f)18 mN/m. Image sizes are 800 x 430 µm, ~ 40x magnifcation.

Figure S17.Hysteresis effect on the isoterm G-3(Peg-Benz).

S1