Article pubs.acs.org/Macromolecules
Size Control of Spherical and Anisotropic Fluorescent Polymer Nanoparticles via Precise Rigid Molecules Friederike Schütze, Marina Krumova, and Stefan Mecking* Chair of Chemical Materials Science, Department of Chemistry, University of Konstanz, 78464 Konstanz, Germany S Supporting Information *
ABSTRACT: Highly monodisperse block copolymers allow for the preparation of luminescent particles with sizes reflecting the oligomer chain length. Self-organization in tetrahydrofuran/methanol leads to anisotropic nanorods with a thickness corresponding directly to the oligomer length (up to 14 nm for 21-mers). As a prerequisite for the realization of this concept, syntheses of defect-free poly(phenylene ethynylene)s with unprecedented chain length up to 43 repeat units were developed. Absorption and emission wavelength in solution continue to increase with increasing chain length, and do not converge until the 43-mer.
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quinoline),14−16 polythiophene,17−20 polyfluorene,21,22 poly(phenylene vinylene),23−25 poly(phenylene ethynylene),26 and poly(p-phenylene).27 However, syntheses of those polymers afford either polymers with rather broad molecular weight distributions, which is not favorable since different hydrophilicto-hydrophobic ratios in the polymer chain result in different supramolecular structures, or low molecular weight oligomers. An illustrative exception is Geng et al.’s synthesis of a polyfluorene 64-mer by Suzuki coupling in an iterative binomial approach.28 The obtained oligomers, which feature a reasonable molecular weight distribution of Mw/Mn of 1.09, were not studied further in terms of structure formation. Within the aforementioned range of rod-like conjugated polymers, poly(phenylene ethynylene)s29 stand out in that the repeat units are linear and thus linkages are particularly stiff. The synthesis of monodisperse oligo(arylene ethynylene)s in a step-by-step buildup by Pd-catalyzed Sonogashira crosscoupling has been the subject of numerous reports.30 Their synthesis involved the utilization of complex coupling strategies, mostly orthogonal acetylene protecting groups, one polar and one nonpolar, which makes this approach tedious. Solubility problems of higher oligomers and lacking possibility of chromatographic separation from Glaser coupling byproducts restrict the accessible chain length to fewer than 12 repeat units.31,32 However, investigations on the particle formation properties of block copolymers with different hydrophilic-to-hydrophobic ratios require the utilization of high molecular weight conjugated oligomers. We show that the utilization of appropriate solubilizing groups facilitates the chromatographic separation and allows for the synthesis of highly precise rod-like molecules up to the 43-mer.
INTRODUCTION Conjugated polymer nanoparticles have received increased interest in the past few years due to their favorable photo- and electroluminescent properties that make them attractive candidates for e.g. optoelectronics, live cell imaging, and biosensing.1−8 Gaining control over the particle size and shape is of fundamental interest yet remains a largely unresolved issue. The preparation of such nanoparticles most commonly involves postpolymerization dispersion techniques.2 To obtain nanoparticles in the size regime below ca. 50 nm, which is particularly relevant e.g. for cell imaging, “nanoprecipitation” is frequently employed. A solution of the hydrophobic conjugated polymer in a water-miscible solvent (THF) is injected rapidly into an excess of water to afford highly diluted dispersions of nanoparticles.9 Particle sizes can be varied to some extent by dilution of the polymer solution. For example, highly diluted dispersions of approximately spherical nanoparticles of high molecular weight substituted poly(phenylenevinylene) (MEHPPV) were generated in this fashion. In these particles, the polymer chains are considered kinetically arrested and are probably randomly oriented.10 Note that the mechanism of colloidal stabilization remains unclear here. As a concept to address the aforementioned problem of size control and to gain access to nonspherical shapes, we sought to encode particle dimensions directly via the length of the linear molecules with precise molecular dimension of these building blocks. In order to provide colloidal stability of the derived nanoparticles, these building blocks are employed in the form of block copolymers with a hydrophilic block.
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RESULTS AND DISCUSSION The self-assembly behavior in solution of different classes of rod−coil molecules11−13 with π-conjugated rod blocks has been reported, including polymeric or oligomeric poly(phenyl © XXXX American Chemical Society
Received: March 20, 2015 Revised: May 15, 2015
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DOI: 10.1021/acs.macromol.5b00591 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules Synthesis of Precise Rod Polymers and Coil−Rod− Coil Block Copolymers. The Sonogashira coupling procedure used for the step-by-step synthesis of oligo(phenylene ethynylene)s is challenging since even low amounts of oxygen in the reaction mixtures result in the formation of undesired side products arising from oxidative alkyne dimerization (Glaser coupling). Utilization of orthogonal acetylene protection groups with different polarity is a prominent way to overcome this problem, yet it is associated with numerous synthesis steps. Hydroxymethyl has proven a worthwhile polar acetylene protecting group, providing sufficient polarity for chromatographic separation of the unreacted starting material from mono- and disubstituted products. We found that the use of a long, branched alkoxy side chain permits for omitting any nonpolar protecting group and reduces the amount of required synthesis steps considerably. Ethylhexyl groups provide enhanced solubility to allow for a chromatographic separation of the mono- and dihydroxymethyl compounds from Glaser coupling byproducts and hence for the synthesis of high molecular weight oligomers. Sonogashira coupling of 1 equiv of 3-(2,5-bis((2-ethylhexyl)oxy)-4-iodophenyl)prop-2-yn-1-ol to a diethynylene component resulted in monofunctional oligomers which were coupled with 1,4-bis((2-ethylhexyl)oxy)-2,5-diiodobenzene followed by deprotection with manganese dioxide (Scheme 1).
Repeating those three steps with OPE9 as a starting material gives HO-OPE10, HO-OPE21-OH, OPE21, and HO-OPE22. Because of an insufficient reaction time during the synthesis of HO-OPE21-OH, Iodo-OPE11-OH was likewise obtained in 14% yield. This side product is useful, however, as it can be separated and either be coupled with OPE9 or with OPE21 to afford HO-OPE31-OH and HO-OPE43-OH. All compounds possess an excellent solubility in tetrahydrofuran, dichloromethane, and diethyl ether and could be purified by column chromatography with pentane/ethyl acetate. The nonamer and higher oligomers can be further purified by precipitation in methanol. The molecular structures of the obtained oligomers were confirmed by 1H NMR, size exclusion chromatography (GPC), and matrix-assisted laser desorption ionization time-offlight (MALDI-TOF, Figure 2) measurements (see Supporting Information). The monodisperse nature, that is, a precise molecular structure, is evidenced by the low polydispersity indices (Mw/Mn = 1.01−1.03) obtained in GPC measurements (Figure 1 and Table 1).
Scheme 1. Synthesis of Monodisperse Oligo(phenylene ethynylene)s
Figure 1. GPC traces of the HO-OPEm and HO-OPEm-OH.
Table 1. Polydispersity Indices (Mw/Mn), Absorption and Emission Maxima, and Quantum Yields of the Obtained OPEs
As a first step of the iterative procedure, Sonogashira coupling of p-diethynylbenzene (1) with 2 equiv of 3-(2,5bis((2-ethylhexyl)oxy)-4-iodophenyl)prop-2-yn-1-ol (2) yielded the diprotected trimer HO-OPE3-OH. The hydroxymethyl protective group can be removed readily with activated manganese dioxide and powdered potassium hydroxide in dry ethyl ether under exclusion of light. The obtained trimer OPE3 was coupled with 0.8 equiv of 2, resulting in a mixture of the starting material, the desired monoprotected tetramer HOOPE4 (49%), and the diprotected pentamer HO-OPE5-OH (23%). The polar hydroxymethyl group provides an excellent chromatographic separation behavior of the three components. Sonogashira coupling of 2 equiv of HO-OPE4 with 1,4-bis((2ethylhexyl)oxy)-2,5-diiodobenzene (3) gives HO-OPE9-OH, followed by deprotection to yield OPE9.
OPEm
Mw/Mna
λabs [nm]
λem [nm]
QY
HO-OPE3-OH HO-OPE5-OH HO-OPE7-OH HO-OPE9-OH HO-OPE10 HO-OPE11-OH HO-OPE21-OH HO-OPE22 HO-OPE31-OH HO-OPE43-OH
1.02 1.02 1.02 1.01 1.03 1.05 1.01 1.01 1.03 1.01
396 420 429 434 439 441 450 451 452 453
429 458 468 471 473 473 475 476 477 478
92 96 97 99 97 96 98 99 92 99
Determined by GPC (refractive index detector, 40 °C, THF, vs PS standard). Absorption and emission spectra were recorded in THF, λexc = 380 nm (for further synthesis of HO-OPEf-OH ( f = 7, 11) see Supporting Information). a
Absorption and emission spectra were recorded in tetrahydrofuran. With higher conjugation length, the absorption and emission maxima are distinctively red-shifted (Figure 3). The effective conjugation length (ELC), that is, the saturation of the red-shift, is not reached before the 43-mer (Table 1 and Figure 4). These experimental data exceed by far the values found in theoretical calculations33 and extrapolation from low B
DOI: 10.1021/acs.macromol.5b00591 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 2. Exemplary MALDI-TOF mass spectra of OPE9. Inset: isotope pattern found (bottom) and calculated (top).
Figure 4. Wavelength of absorption (red) and emission (black, λexc = 380 nm) maxima of the obtained OPEs.
molecular weight oligomers31 of 12-mer and 9-mer, respectively. The absorption maxima λabs in solution range between 396 and 453 nm. The emission maxima λem range between 429 and 478 nm with quantum yields between 92 and 99%. The hydroxymethyl protective group is not only useful as a polar tag but also can serve as a functional group for block copolymer synthesis. The obtained monodisperse, dihydroxyterminated OPEs were coupled to α-carboxy-ω-methoxy poly(ethylene glycol) (Mn = 750, 2000, and 5000 g/mol) via DCC coupling (Scheme 2). The resulting block copolymers possess similar narrow molecular weight distributions (Mw/Mn = 1.04−1.08) as the initial rod oligomer, as determined by GPC in THF as a good solvent for both blocks (see Supporting Information). Nanoparticle Synthesis. The obtained amphiphilic triblock copolymers were investigated in terms of their particle formation behavior during rapid mixing, focusing on the influence of the length of the hydrophilic coil and the hydrophobic rod. For the preparation of aqueous particle dispersions, a dilute solution of the block copolymer in tetrahydrofuran was injected manually into an excess of rapidly stirred water (“nanoprecipitation”). The polymer precipitates in the form of nanoparticles, self-stabilized by the hydrophilic PEG. Nanoparticle sizes from PEG n -OPE m-PEGn were determined by dynamic light scattering (DLS) and remained unaltered over several weeks, proving the stability of the dispersions obtained. The concentration of the polymer in tetrahydrofuran was varied between 0.005 and 1 wt % (Figure 5).
Non-PEGylated HO-OPE21-OH forms larger particles (25− 80 nm), increasing in size with increasing concentration of the polymer in tetrahydrofuran (Figure 5, left). Furthermore, the dispersions tend to macroscopic precipitation of the polymer at higher concentrations (>0.1 wt %). Covalent attachment of αcarboxy-ω-methoxy poly(ethylene glycol) (Mn = 750 g/mol) leads to a decrease in size of the obtained nanoparticles from PEG750-OPE21-PEG750 of 16−20 nm (c ≤ 0.1 wt %), showing the very effective stabilization of the nanoparticles by the poly(ethylene glycol) blocks. Solely above 0.1 wt %, particle size becomes dependent on the concentration again and relatively increases abruptly to 80 nm. With an increased PEG length (Mn = 2000 g/mol), particles sizes remain comparatively small (
