Communication pubs.acs.org/cm
Secrets of Plasma-Deposited Polyoxazoline Functionality Lie in the Plasma Phase Melanie N. Macgregor,* Andrew Michelmore, Hanieh Safizadeh Shirazi, Jason Whittle, and Krasimir Vasilev* School of Engineering, Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia S Supporting Information *
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iocompatibility, stability, and nonfouling properties have propelled polyoxazolines (POx) to the forefront of biomedical research1 as a particularly attractive alternative to the gold standard polyethylene glycol in areas such as drug delivery, tissue engineering and medical implants.2,3 Moreover, unearthing POx dielectric character has opened new perspectives for this unique class of polymers such as in enhancing polymer solar cell efficiency4,5 and improving light emitting diode performance.6 Yet, the conventional organic synthesis of POx has several disadvantages which are an obstacle to POx widespread utilization. Traditionally, POx are synthesized via ring opening polymerization (ROP), a multistep synthesis which uses organic solvents and is sensitive to the presence of nucleophiles, notably water. In addition, generating high molecular weight polymers is difficult7 and an additional step is required to assemble the polymer into a thin film.8 Importantly, ROP inherently consumes the oxazoline rings, which could otherwise be used in binding reactions.9 A solution to these challenges can be the use of plasma deposition to generate POx based coatings.10,11 Plasma deposition of organic thin films is attractive because it is a rapid, single step process that is also solvent free and readily scalable. These films adhere strongly to practically any type of substrate materials which is critical for coating medical devices, but also for production of robust films for clean energy and optical applications.12 Recent studies established that plasma deposited POx (PPOx) films not only feature properties comparable to those of conventional POx films (e.g., biocompatibility and low biofouling) but also have additional attributes ascribed to the retention of the oxazoline ring.13 Most distinctively, PPOx films readily bind biomolecules at room temperature via the formation of covalent bonds with carboxylic acid groups,14,15 which is highly valuable in many biomedical applications ranging from biosensing16 to cell therapies.17 To fully benefit from the unique properties of the PPOx films, it is important to mechanistically reveal how these coatings are deposited from the plasma phase. Herein, we used in situ mass spectrometry to explore the fragmentation of 2-methyl-2oxazoline (MeOx), Figure 1a, in the plasma phase across a useful input power range (2 to 50 W). Together with the chemical analysis of the final PPOx films surface, as determined via XPS and ToF, these results were used to identify the processes responsible for the formation of key chemical functions. In classic organic chemistry, elemental electronegativity, bond accessibility, and dissociation energies (Figure 1b−d)18 © 2017 American Chemical Society
Figure 1. (a) MeOx chemical formulas with bond labels. (b) Elemental electronegativity. (c) Bond accessibility and (d) energy scale. (e) Percentatge of plasma electrons with eV superior to that of the corresponding chemical bonds.
together determine which molecular bonds are most likely to break and participate in chemical reactions. Cationic ROP of MeOx, for instance, propagates via breakage of the C−O bond, 3b, which is not the weakest bond, but is the most accessible and adjacent to the most electronegative atom. Additional factors must be considered to define how the MeOx precursor (Figure 1a) is fragmented during plasma deposition. In MeOx, the strongest bond is CN, at 6.4 eV. This is 1 order of magnitude less than the peak ion energy (Figure S1), but comparable to the energy of electrons (Te = 3 eV), which are responsible for bond scission in the plasma phase (Figure S1). Therefore, although only 9% of the electrons have an energy greater than that of the CN bond (Figure 1e), it is theoretically possible for any of the bonds present in MeOx to be readily cleaved by electron impact in the plasma phase. Neutral and positively charged species formed in MeOx plasma were investigated via mass spectrometry. Figure 2 show the electron impact (EI) mass spectra (MS) for MeOx acquired using RF powers of 0 (no plasma), 2, 5, 15, 30, and 50 W. The fragmentation pathways proposed to assign peaks present in the EI spectra are shown in Scheme 1 and discussed in detail in the Supporting Information. Without plasma, close to 20% of MeOx ([M]+•, 85 m/z) remains intact. While the degree of precursor dissociation (Figure S3) increases with plasma power, intact [M]+ is still present, in concentrations significantly greater than previously reported for other precursors.19,20 Other abundant fragments are nitriles and isocynate species resulting from the breakage of bonds adjacent to the MeOx quaternary center regardless of their theoretical strength or accessibility, as previously observed for the plasma fragmentation of other cyclic monomers such as terpenes.19 Received: July 18, 2017 Revised: September 22, 2017 Published: September 28, 2017 8047
DOI: 10.1021/acs.chemmater.7b03023 Chem. Mater. 2017, 29, 8047−8051
Communication
Chemistry of Materials
resulting from 2a bond fission. As power increases, the 72 m/z peak disappears while signals for smaller fragments at 28, 42, and 44 m/z become visible corresponding to species obtained from the scission of the protonated oxazoline ring, as depicted in Scheme 2. The proposed pathways for the formation of species with high m/z are also shown in Scheme 2. A significant oligomeric peak corresponding to [2M + H]+ is found at 171 m/z for powers above 30 W. The oligomer concentration in the plasma is comparable to that of the monomer. Another peak corresponding to [2ring + H] is found at 141 m/z, whose relative intensity decreases with power. This peak is also considered to be the parent peak of the peak at m/z = 114, which is possibly formed by loss of CH2CH2. Another notable peak is present at m/z = 100, which could be formed from the recombination of the ring with a CH3· radical. The relative concentration of most ring-containing species (m/z = 72, 86, 87, 100, 114) decreases with power, in good agreement with observations of the surface of PPOx films in previous reports.13 It is worth noting, however, that the formation of oligomers at high powers counterbalance the loss of [MH]+. In contrast, the concentration of many other functionality-rich species is triggered by the plasma, for instance the nitriles at 28, 42, and 56 m/z, but also the aldehyde CH2CHO+ and amide NHCHO+ at 43 and 44 m/z (Figure S4). To make the link between the species formed in the plasma phase and the building blocks of the resultant PPOx films, surface chemistry was assessed by XPS (Figures S5 and S6) and ToF-SIMS. High resolution C 1s and N 1s XPS analysis indicate complex atomic environment with single and multiple bonded carbon and nitrogen, in good agreement with the mass spectrometry results. While the peak intensity for single CC (285 eV) and amine CN component (399.1 eV) increased with power, those of functional NCO (288.2 and 400 eV) components decreased. Interestingly, quite a few fragments found in the TOF-SIMS spectra of the PPOx surface correspond to species identified in the plasma phase while others were specific to the plasma polymer film itself Table 1. The latter are pure hydrocarbons, originating from recombination processes occurring at the surface as the PPOx film is formed. These peaks typically increase in relative intensity as the plasma power increases, as shown in the subtractive plot presented in Figure 4a. Careful analysis of the high resolution spectra revealed that most of the other peaks actually consist of more than one fragment, one of which is generally also a pure hydrocarbon (Table 1). Examples of dual and triple peaks at 28 and 55 m/z are shown in Figure 4. For instance, the 28 m/z peak is split into CH2N and C2H2+, in good agreement with the fragmentation pathways proposed in Scheme 2. The ToF-SIMS data further indicate that the nitrile is the principal species at this m/z. In all cases (Figure S7), increasing power reduces the amounts of functional aminated and oxygenated species in favor of inert hydrocarbon fragments. Nonetheless, several of the most important peaks correspond to functional species. One important peak is the aldehyde C2H3O+ (m/z = 43). Yet, only traces of fragments with m/z = 43 were present in the plasma phase. Considering the structure of the open ring configuration of POx(TOC) we therefore hypothesize this aldehyde fragment originates from regions of the PPOx film with a structure resembling that of conventional POx structure, formed post plasma by surface cross-linking processes. The nitrile C4H4N+ m/z = 42, for which 2 independent formation pathways were identified in Scheme 2, is also an abundant fragment in the ToF-SIMS spectra, closely
Figure 2. EI mass spectra for MeOx without plasma, bottom trace, and with increasing plasma powers from 2 to 50 W.
Scheme 1. Proposed Fragmentation Pathways for the EI MS of PPOxa
a
Reactions with purple arrows are enhanced by action of the plasma.
MS taken in positive ion mode over the RF plasma power range of 2 to 50 W are shown in Figure 3. The dominant peak observed at all powers was that of the protonated molecule [M + H]+ at 86 m/z. Notably, the protonated monomer represent between 25 and 70% of the total spectral area, which is significantly more than has been reported for other precursors.20,21 Together with the EI results, this demonstrates that under the experimental conditions investigated here, the oxazoline precursor is very stable. MeOx has already been deemed thermally stable,22 resistant to nucleophiles, bases, radicals, and weak acids23 and also to hydrolysis and oxidation.24 Here we show that it is also fairly resistant to plasma assisted fragmentation. Both higher and lower mass species were also present but generally in much lower concentration. At low RF power, the main lower mass species are 55 (Scheme 2) and 72 m/z, which is assigned to the protonated oxazoline ring, [Ring + H]+, 8048
DOI: 10.1021/acs.chemmater.7b03023 Chem. Mater. 2017, 29, 8047−8051
Communication
Chemistry of Materials
Figure 3. Positive ion MS obtained from plasma of MeOx at 2, 5, 15, 30, and 50 W.
Scheme 2. Positive Ion Mass Spectrometry Fragmentation Pathways
the 43 m/z species as the principal component of the ToFSIMS spectra. This could explain why PPOx shares the low fouling properties and biocompatibility of POx produced by conventional polymerization.14 However, mass spectrometry of the plasma phase indicates that these fragments were not the only constituents of the plasma phase. Fragments corresponding to functional species such as nitrile, imines, and oxazoline rings (and NCO isocyanates) identified in the TOF SIMS spectra were also found in the neutral and positive ion spectra of the plasma mass spectrometry analysis. It therefore appears that the availability of these chemical functionalities in the coatings is the result of rearrangements and grafting events occurring during plasma deposition. The plasma assisted grafting of these reactive groups explains the unique reactivity of PPOx toward biomolecules and other ligands (e.g., nanoparticles) containing carboxylic acid functional groups. This work demonstrates there is a link between the chemistry
followed by C2H6N m/z = 44 and CH4N (m/z = 30). Since only traces of these two imine species were present in the plasma phase, we hypothesize that they result from the postplasma protonation of the nitriles m/z = 28 and 42. Finally, the most abundant fragment containing both N and O is the protonated precursor itself (m/z = 86), accompanied by the deprotonated precursor (m/z = 84), and the deprotonated ring m/z = 70. The relative abundance of these species compared to that of the C3H3O aldehyde is plotted in Figure 4d as a function of plasma power. While the overall amount of both aldehyde and CNO species decreases with power, the % of ring retention, remains between 23 and 28%.
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CONCLUSION Based on the ToF-SIMS results, the PPOx films appear to partially consist of same the chemical functions as those found in conventional polyoxazoline, as indicated by the presence of 8049
DOI: 10.1021/acs.chemmater.7b03023 Chem. Mater. 2017, 29, 8047−8051
Communication
Chemistry of Materials
Table 1. Summary of Fragment Identified From ToF-SIMS and Plasma Mass Spectrometry, Showing the Species Specific to Surface or Plasma and Shared ones ToF SIMS m/z
Hydrocarbon
15 27 28 29 30 39 41 42 43 44 55 56 57 70 72 84 86 100 141 171
CH3+ C2H3+
Plasma mass spectrometry Functional
Shared
Plasma only CHN
C2H4+•, NCH2+ C2H5+
CH3N+•, CHO+ CH4N+
+
C3H3 C3H5+ C3H6+• C3H7+ C4H7+ C4H9+
C2H3N+ C2H4N+ CH2CHO+ CH3CHO+•, NHCHO+ CH3CNCH2+• CH3CNCH2+
C2H5N+• C2H6N+ C3H3O+
HNCO+•
C3H7N+•, C3H5O+ [ring − H]+ [ring + H]+ [M − H]+ [M + H]+ [M + CH3]+ [2ring + H]+ [2M + H]+
Figure 4. (a) Differential positive ion ToF SIMS spectra between PPOx films deposited at 2 and 50 W, amine and oxygen containing species are more represented at low power. (b) High resolution 55 m/z and (c) 28 m/z peaks, primarily hydrocarbon, and nitrile respectively, for PPOx films deposited at 2 W (top) and 50 W (bottom). (d) Variation of the relative peak intensity with deposition power for aldehyde (43 m/z) and ring containing species (left axis) and corresponding ratio of ring retention compared to open ring structure (right axis).
of the plasma phase and that of the deposited film that can be assessed by real time mass spectroscopy. This can be used to create unique materials with tailored properties exceeding those obtainable by “traditional” chemistry from a variety of precursors.
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Experimental section, peak ion and electron energy data, EI background MS and degree of dissociation, positive ion MS, detailed XPS and ToF SIMS analysis (PDF)
AUTHOR INFORMATION
Corresponding Authors
*M. N. Macgregor. E-mail:
[email protected]. *K. Vasilev. E-mail:
[email protected].
ASSOCIATED CONTENT
S Supporting Information *
ORCID
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.chemmater.7b03023.
Melanie N. Macgregor: 0000-0002-8671-181X Andrew Michelmore: 0000-0003-3215-8841 Krasimir Vasilev: 0000-0003-3534-4754 8050
DOI: 10.1021/acs.chemmater.7b03023 Chem. Mater. 2017, 29, 8047−8051
Communication
Chemistry of Materials Notes
Surfaces for Stem Cell Research; John Wiley & Sons, Inc., 2016; pp 199−232. (18) Huheey, J. E.; Keiter, E. A.; Keiter, R. L.; Medhi, O. K. Inorganic Chemistry: Principles of Structure and Reactivity; Pearson Education, 2006. (19) Ahmad, J.; Bazaka, K.; Whittle, J. D.; Michelmore, A.; Jacob, M. V. Structural Characterization of γ-Terpinene Thin Films Using Mass Spectroscopy and X-Ray Photoelectron Spectroscopy. Plasma Processes Polym. 2015, 12, 1085−1094. (20) Saboohi, S.; Al-Bataineh, S. A.; Safizadeh Shirazi, H.; Michelmore, A.; Whittle, J. D. Continuous-Wave RF Plasma Polymerization of Furfuryl Methacrylate: Correlation between Plasma and Surface Chemistry. Plasma Processes Polym. 2017, 14, 1600054. (21) Hazrati, H. D.; Whittle, J. D.; Vasilev, K. A Mechanistic Study of the Plasma Polymerization of Ethanol. Plasma Processes Polym. 2014, 11, 149−157. (22) Loo, Y. F.; O’Kane, R.; Jones, A. C.; Aspinall, H. C.; Potter, R. J.; Chalker, P. R.; Bickley, J. F.; Taylor, S.; Smith, L. M. Deposition of HfO2 and ZrO2 Films by Liquid Injection MOCVD Using New Monomeric Alkoxide Precursors. J. Mater. Chem. 2005, 15, 1896− 1902. (23) Wuts, P. G. M. Protective Groups in Organic Synthesis; John Wiley & Sons Inc, 1991. (24) Wiley, R. H.; Bennett, L. L. The Chemistry of the Oxazolines. Chem. Rev. 1949, 44, 447−476.
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank UniSA, the Humboldt foundation, NHMRC (APP1122726), the Australian Research Council (DP15104212), and the Australian government for funding.
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REFERENCES
(1) Hoogenboom, R. Poly(2-oxazoline)s: a Polymer Class with Numerous Potential Applications. Angew. Chem., Int. Ed. 2009, 48, 7978−94. (2) Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U. S. Poly(ethylene glycol) in Drug Delivery: Pros and Cons as well as Potential Alternatives. Angew. Chem., Int. Ed. 2010, 49, 6288−308. (3) Chapman, R. G.; Ostuni, E.; Takayama, S.; Holmlin, R. E.; Yan, L.; Whitesides, G. M. Surveying for Surfaces that Resist the Adsorption of Proteins. J. Am. Chem. Soc. 2000, 122, 8303−8304. (4) Nam, S.; Seo, J.; Woo, S.; Kim, W. H.; Kim, H.; Bradley, D. D. C.; Kim, Y. Inverted Polymer Fullerene Solar Cells Exceeding 10% Efficiency With Poly(2-Ethyl-2-Oxazoline) Nanodots on ElectronCollecting Buffer Layers. Nat. Commun. 2015, 6, 8929. (5) Chen, W.; Zhu, Y.; Yu, Y.; Xu, L.; Zhang, G.; He, Z. Low Cost and Solution Processed Interfacial Layer Based on Poly(2-ethyl-2oxazoline) Nanodots for Inverted Perovskite Solar Cells. Chem. Mater. 2016, 28, 4879−4883. (6) Lin, H.; Zhu, L.; Huang, H.; Reckmeier, C. J.; Liang, C.; Rogach, A. L.; Choy, W. C. H. Efficient Near-Infrared Light-Emitting Diodes Based on Organometallic Halide Perovskite-Poly(2-Ethyl-2-Oxazoline) Nanocomposite Thin Films. Nanoscale 2016, 8, 19846−19852. (7) Sedlacek, O.; Monnery, B. D.; Filippov, S. K.; Hoogenboom, R.; Hruby, M. Poly(2-oxazoline)s–Are They More Advantageous for Biomedical Applications than Other Polymers? Macromol. Rapid Commun. 2012, 33, 1648−62. (8) Morgese, G.; Benetti, E. M. Polyoxazoline Biointerfaces by Surface Grafting. Eur. Polym. J. 2017, 88, 470−485. (9) Schmidt, D. L.; Coburn, C. E.; DeKoven, B. M.; Potter, G. E.; Meyers, G. F.; Fischer, D. A. Water-Based Non-Stick Hydrophobic Coatings. Nature 1994, 368, 39−41. (10) Ramiasa, M. N.; Cavallaro, A. A.; Mierczynska, A.; Christo, S. N.; Gleadle, J. M.; Hayball, J. D.; Vasilev, K. Plasma Polymerised Polyoxazoline Thin Films for Biomedical Applications. Chem. Commun. 2015, 51, 4279−4282. (11) Bhatt, S.; Pulpytel, J.; Mirshahi, M.; Arefi-Khonsari, F. Cell Resistant Peptidomimetic Poly (2-ethyl-2-oxazoline) Coatings Developed by Low Pressure Inductively Excited Pulsed Plasma Polymerization for Biomedical Purpose. Plasma Processes Polym. 2015, 12, 519−532. (12) Wong, W. W. H.; Rudd, S.; Ostrikov, K.; Ramiasa-MacGregor, M.; Subbiah, J.; Vasilev, K. Plasma Deposition of Organic Polymer Films for Solar Cell Applications. Org. Electron. 2016, 32, 78−82. (13) Macgregor-Ramiasa, M. N.; Cavallaro, A. A.; Vasilev, K. Properties and reactivity of polyoxazoline plasma polymer films. J. Mater. Chem. B 2015, 3 (30), 6327−6337. (14) Cavallaro, A. A.; Macgregor-Ramiasa, M. N.; Vasilev, K. Antibiofouling Properties of Plasma-Deposited Oxazoline-Based Thin Films. ACS Appl. Mater. Interfaces 2016, 8, 6354−6362. (15) Zanini, S.; Zoia, L.; Dell’Orto, E. C.; Natalello, A.; Villa, A. M.; Pergola, R. D.; Riccardi, C. Plasma Polymerized 2-Ethyl-2-Oxazoline: Chemical Characterization and Study of the Reactivity toward Different Chemical Groups. Mater. Des. 2016, 108, 791−800. (16) Macgregor-Ramiasa, M.; McNicholas, K.; Ostrikov, K.; Li, J.; Michael, M.; Gleadle, J. M.; Vasilev, K. A platform for Selective Immuno-Capture of Cancer Cells from Urine. Biosens. Bioelectron. 2017, 96, 373−380. (17) Macgregor-Ramiasa, M. N.; Vasilev, K. Plasma Polymer Deposition: A Versatile Tool for Stem Cell Research. In Advanced 8051
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