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Assembly of Branched Polyhedral Oligomeric Silsesquioxane Nanoparticles Prepared via Strain-Promoted 1,3-dipolar Cycloadditions Petr A. Ledin, Weinan Xu, Frédéric Friscourt, Geert-Jan Boons, and Vladimir V. Tsukruk Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.5b01764 • Publication Date (Web): 01 Jul 2015 Downloaded from http://pubs.acs.org on July 7, 2015
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Langmuir
Branched Polyhedral Oligomeric Silsesquioxane Nanoparticles Prepared via Strain-Promoted 1,3-dipolar Cycloadditions Petr A. Ledin,a Weinan Xu,a Frédéric Friscourt,b Geert-Jan Boons,b,c and Vladimir V. Tsukruk*a a
School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA
b
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, 30602, USA c
Department of Chemistry, University of Georgia, Athens, Georgia 30602, USA
KEYWORDS: Cyclooctyne, functionalized POSS, SPAAC, Star-like molecules
Conjugation of small organic molecules and polymers to polyhedral oligosilsesquioxane (POSS) cores results in novel hybrid materials with unique physical characteristics. We report here an approach in which star-shaped organic-inorganic scaffolds bearing eight cyclooctyne moieties can be rapidly functionalized via strain-promoted azide-alkyne cycloaddition (SPAAC) to synthesize a series of nearly monodisperse branched coreshell nanoparticles with hydrophobic POSS cores and hydrophilic arms.
We
established that SPAAC is a robust method for POSS core octafunctionalization with the reaction rate constant of 1.9×10-2 M-1s-1.
Functionalization with polyethylene glycol
(PEG) azide, fluorescein azide, and unprotected lactose azide, gave conjugates, which represent different classes of compounds: polymer conjugates, bioconjugates, and fluorescent dots. These resulting hybrid compounds were preliminary tested for their ability to self-assemble in solution and at the air-water interface. We observed the formation of robust smooth Langmuir monolayers with diverse morphologies. We found that polar lactose moieties are completely submerged into the subphase whereas the relatively hydrophobic fluorescein arms had extended conformation at the interface, and PEG arms were partially submerged.
Finally, we observed the formation of stable
micelles with sizes between 70 and 160 nm in aqueous solutions with size and morphology of the structures dependent on the molecular weight and the type of the peripheral hydrophilic moieties.
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INTRODUCTION Well-defined organic-inorganic cubic cage nanostructures of general formula RSiO3/2, termed polyhedral oligosilsesquioxanes (POSS), have become attractive functional cores due to their thermal stability, monodispersity, ease of preparation and covalent functionalization.1-3 Conjugation of small organic molecules and polymers to POSS core results in novel hybrid materials with unique physical characteristics and improved thermal, mechanical, and optical properties.4 For example, tethering of organic chromophores to POSS core was shown to increase their thermal- and photostability, enhance their optical properties, and impart solution processability, allowing the manufacture of nanocomposites by common top down fabrication methods.5-8 Furthermore, the materials where the POSS core was modified with polyethylene glycol (PEG) or ionic liquid (IL) moieties, were utilized for energy storage and conversion.9-11 The conjugation of biologically active molecules to the nontoxic and biocompatible POSS core is highly desirable for applications in drug delivery and bio imaging where multivalency is required.12 Star-like molecules with inorganic POSS core and organic arms of polymeric or monomeric nature are of particular interest, as they possess unique properties that are not observed in their linear counterparts.13 Branched POSS-based materials have shown self-assembly properties in bulk, in solution, and at interfaces.14-15 Depending on conditions such compounds can exist as unimolecular vesicles or aggregate into polymersomes.16-17 Star-like architecture also defines the bulk properties of these materials providing three-dimensional scaffolding for supramolecular assembly and crosslinking.18-19 Finally, an increased free volume in thin films prepared from starshaped POSS conjugates lowers the dielectric constant, allows for unhindered azobenzene photoisomerization, and improves antifouling properties.20-22 The traditional synthetic protocols, usually exploited for the chemical modification of POSS cores, such as hydrosilylation, often require harsh reaction conditions, prolonged reaction times and may lead to mixtures of polydisperse partially modified cores.23-24 In contrast, “click” reactions such as thiol-ene/yne additions, formation of disulfide bonds, Diels-Alder reactions, and 1,3-dipolar cycloadditions can be highly efficient and tolerate a wide range of functional groups facilitating the practical
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construction of POSS-based hybrid nanoparticles.13,
25
Copper catalyzed azide-alkyne
cycloaddition (CuAAC), the most explored of these click reactions; can also be used for grafting polymers, dyes, peptides, and carbohydrates onto the POSS core.26-30 On the other hand, strain-promoted azide-alkyne cycloadditions (SPAAC) offer advantages similar to CuAAC, but do not require either the use of toxic copper catalyst or extensive optimization of reaction conditions.31-32 Moreover, the stable cyclic alkynes, such as 4-dibenzocyclooctynol (DIBO), are easy to prepare and react rapidly with 1,3dipoles (azides, nitrones, nitrile oxides, and diazo-compounds) and 1,2,4,5-tetrazines.3336
Because SPAAC requires no catalyst, generates a stable triazole moiety, and gives
no byproducts it is increasingly employed during construction and functionalization of hydrogels, polymers, and dendrimers.37-40 Recently Su and Li et. al demonstrated the versatility of SPAAC by sequential multifunctionalization of POSS scaffolds where SPAAC has been used in tandem with other orthogonal click reactions to produce linear and cyclic polymeric surfactants with hydrophilic POSS head groups.41-44 However, to the best of our knowledge, no star-like compounds have been synthesized using this efficient
synthetic
approach
with
potentially
practical
multifunctional
hybrid
nanomaterials. We therefore contemplated that a cubic octavalent oligosilsesquioxanes bearing strained alkynes as corner functionalities could serve as a functional scaffold for the facile construction of star-like or branched core-shell nanoparticles via SPAAC approach with minimal incomplete derivatization and product inhomogeneity. In this study, we demonstrated that this approach can be efficiently applied to coupling azidecontaining fluorescent dyes and hydrophilic moieties such as carboxyfluorescein, lactose, and PEGs to give a library of nearly monodisperse branched organic-inorganic hybrid nanoparticles a few nanometers in diameter under mild reaction conditions. The conjugation of hydrophilic moieties to the POSS-based scaffold resulted in diverse selfassembly behavior at air-water interface as well as in aqueous solutions driven by the hydrophobic POSS core with the morphology of the structures dependent on the molecular weight and the type of the peripheral hydrophilic moieties.
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EXPERIMENTAL SECTION Materials. Plastics.
Octaammonium POSS hydrochloride was purchased from Hybrid
N,N-diisopropylethylamine (99.5%) was purchased from Sigma-Aldrich.
Dichloromethane (DCM) was distilled over calcium hydride prior to use. The azidomodified fluorescein 4 was prepared as described previously.45 The 2-azidopentyl β-Dgalactopyranosyl-(1→4)-β-D-glucopyranoside (5) and azido-PEG derivatives 6 and 7 were prepared as described previously.39 Reactions were performed at room temperature (20-22°C), unless stated otherwise. NMR. The NMR spectra were recorded on Varian Mercury (300, 500 MHz) and Bruker DMX 400 (400 MHz) spectrometers at 25°C. Chemical shifts are reported in δ units, parts per million (ppm) downfield from TMS, spectra are referenced by solvent signals. Only proton spectra are provided for SPAAC conjugates due to complexity of carbon spectra because of 1,2,3-triazole regioisomeric mixture. Molecular weight. Mass spectra were obtained using MALDI-TOF instruments (ABISciex 5800 MALDI-TOF-TOF) with 2,5-dihydroxybenzoic acid or dithranol as a matrix in positive reflector mode unless stated otherwise. The Shimadzu LCMS-IT-TOF was used to obtain and ESI-MS spectrum in negative mode. Monoisotopic masses are provided unless stated otherwise. Gel permeation chromatography (GPC) analysis was performed on Shimadzu instrument equipped with a LC-20AD HPLC pump and a refractive index detector (RID-10A, 120 V). THF was used as the mobile phase at the flow rate of 1.0 mL/min at 35 °C. One Phenogel 5 µm linear column and one Phenogel 5 µm 10E4A mixed bead column were used in series.
Molecular weights were
calculated against polystyrene standards. TEM.
The TEM was done using a JEOL 100CX operated at 100 kV with
samples drop cast on carbon–formvar-coated copper grids (Ted Pella, Inc.).
The
excess of water was removed by touching the edge of the grids with a small piece of filter paper (Whatman). The grids were allowed to dry at room temperature followed by staining with a drop of 2% (wt.) phosphotungstic acid (freshly prepared in Nano pure water and filtered through a 0.2 µm filter membrane). After 2 min, excess staining agent was removed by blotting with filter paper, and the grids were further dried at ambient temperature for 15 min and used for TEM imaging.
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DLS. Dynamic light scattering measurements were performed using a laser light scattering spectrometer (Malvern Zetasizer Nano ZS) at 25 °C. For each sample, 12 to 14 replicates were obtained to determine the average and mean sizes and size distribution.
The polydispersity of sizes of polymeric self-assembled structures
(Polydispersity index) equals to (σ/d)2, where σ is a standard deviation and d is the mean diameter of the particles.
Critical micellar concentration was determined by
observing a count rate for samples with different concentrations of 8-11 in water prepared by serial dilution. Langmuir-Blodgett deposition. A KSV2000 LB minitrough filled with Nanopure water (18.2 MΩ cm) at room temperature was used for LB deposition. The surface pressure was measured with a platinum Wilhelmy plate attached to a pressure sensor. The solution of compounds (0.1 mg/mL in 10% MeOH in CHCl3 (vol.), or EtOH:CHCl3, 9:1, (v:v) for compound 8) was carefully spread over the water surface and the monolayer was left for 30 min to allow for evaporation of the organic solvent and equilibration. The Langmuir monolayer was then compressed at a rate of 5 mm/min to reach a surface pressure of 1 or 4 mN/m.
The monolayer was transferred onto
precleaned silicon slide at the air-water interface by pulling the substrate up vertically at a rate of 1 mm/min. Silicon wafers were cleaned with piranha solution (3:1 concentrated sulfuric acid and hydrogen peroxide mixture. Caution strong oxidizer!) according to the known procedure.46 Then wafers were rinsed thoroughly with nanopure water and dried with a nitrogen stream. The value of the limiting cross-sectional area in condensed state, Ao, was derived from pressure-area isotherms by using the tangent line corresponding to the steepest rise in the surface pressure. AFM. AFM images were obtained using a Dimension-3000 (Digital Instruments) microscope in the ‘‘light’’ tapping mode according to the well-established procedure.47 Image processing was performed using NanoScope 1.40 and Gwyddion 2.36 software. Spectrophotometry. The Uv-Vis spectra were recorded on Shimadzu UV-2450 spectrophotometer in 1 cm quartz spectrophotometric cells. Fluorescence spectra were acquired on Shimadzu RF-5301pc spectrofluorophotometer. obtained on Bruker Vertex 70 spectrometer in KBr pellets.
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FTIR spectra were
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Molecular Modeling.
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Molecular models were built with Accelrys Materials
Studio 3.1. The structures were optimized using the Discover tool (CVFF force field). The minimal cross section (molecular area) was calculated from the smallest sectional diameter of the molecules with hydrophilic arms “submerged” into the subphase. Spectroscopic ellipsometry. Spectroscopic ellipsometry was performed with a M-2000U ellipsometer (Woollam). The spectral range was 245-1000 nm (D2 and QTH lamps). Ellipsometry data from all samples were acquired at 65°, 70°, and 75° angles of incidence over the spectral range. The monolayers were fitted with a three layer model which consists of a silicon substrate, a silicon oxide layer (2 nm layer thickness), and a Cauchy layer (MSE
