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Cite This: Anal. Chem. XXXX, XXX, XXX−XXX

Power of Ultra Performance Liquid Chromatography/Electrospray Ionization-MS Reconstructed Ion Chromatograms in the Characterization of Small Differences in Polymer Microstructure Ruben Epping,† Ulrich Panne,†,‡ and Jana Falkenhagen*,† †

Bundesanstalt für Materialforschung und−prüfung (BAM), Richard-Willstätter-Straße 11, 12489 Berlin, Germany Chemistry Department, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, D-12489 Berlin, Germany

‡

S Supporting Information *

ABSTRACT: From simple homopolymers to functionalized, 3dimensional structured copolymers, the complexity of polymeric materials has become more and more sophisticated. With new applications, for instance, in the semiconductor or pharmaceutical industry, the requirements for the characterization have risen with the complexity of the used polymers. For each additional distribution, an additional dimension in analysis is needed. Small, often isomeric heterogeneities in topology or microstructure can usually not be simply separated chromatographically or distinguished by any common detector but affect the properties of materials significantly. For a drug delivery system, for example, the degree of branching and branching distribution is crucial for the formation of micelles. Instead of a complicated, time-consuming, and/or expensive 2D-chromatography or ion mobility spectrometry (IMS) method, that also has its limitations, in this work, a simple approach using size exclusion chromatography (SEC) coupled with electrospray ionization (ESI) mass spectrometry is proposed. The online coupling allows the analysis of reconstructed ion chromatograms (RICs) of each degree of polymerization. While a complete separation often cannot be achieved, the derived retention times and peak widths lead to information on the existence and dispersity of heterogeneities. Although some microstructural heterogeneities like short chain branching can for large polymers be characterized with methods such as light scattering, for oligomers where the heterogeneities just start to form and their influence is at the maximum, they are inaccessible with these methods. It is also shown that with a proper calibration even quantitative information can be obtained. This method is suitable to detect small differences in, e.g., branching, 3D-structure, monomer sequence, or tacticity and could potentially be used in routine analysis to quickly determine deviations.

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widespread in polymer analysis is size exclusion chromatography (SEC),2 which became available for ultra performance liquid chromatography (UPLC)3 also in recent years.4 For this chromatographic mode, a porous stationary phase is used. The stationary and mobile phase combination is chosen so that ideally no enthalpic interaction of the analytes with the stationary phase occurs. The separation only depends on entropic interactions, specifically by conformational changes of the polymer chains when entering the pores. Because smaller polymer coils can enter more pores than larger coils, this leads to a separation by hydrodynamic volume. The hydrodynamic volume is the characteristic dimension for the size of a molecule in solution. In simpler cases, this can be translated to a separation by molar mass by applying a calibration. In complexes cases, where the sample contains, for example, linear and branched polymers at the same time, this translation becomes impossible, because different topologies can vary in

ith increasing requirements in the properties of modern functional materials, the knowledge of the detailed chemical structure of polymers is becoming more and more important. While in the past the measurement of bulk properties and a rough analysis of the molar mass distribution was sufficient to fulfill the demands of the industry, nowadays, detailed information about the composition and chain structure of polymers is required. Simple materials such as everyday objects or construction materials consist commonly of a single homopolymer with a mass distribution. More sophisticated polymeric materials developed for the application in the fields of, e.g., biomedicine, smart materials, or the semiconductor industry, often consist of more than one polymer, copolymers, different functionalities, topological or microstructural isomers, and numerous other possible structural differences.1 The difficulty in the characterization arises from the superposition of these often small differences in various distributions. Every additional distribution requires another dimension in the analysis and multiplies the accruing data. In most cases, this analytical challenge is met by a combination of a separation and detection step. Often, the separation is achieved via liquid chromatography. Particularly © XXXX American Chemical Society

Received: December 14, 2017 Accepted: February 5, 2018 Published: February 5, 2018 A

DOI: 10.1021/acs.analchem.7b05214 Anal. Chem. XXXX, XXX, XXX−XXX

Article

Analytical Chemistry

separated poly-L-lactide and poly-D,L-lactide.20 They found an increasing gap in CCS values for higher degrees of polymerization. Scrivens and co-workers could distinguish between isomeric polyethylene glycols (PEG) with different end groups.21 The end groups had to differ significantly to achieve a proper separation. Grayson and co-workers, De Pauw and coworkers, and Clemmer and co-workers found different CCSs for architectural isomers.22−25 They used the unfolding of multiply charged polymer coils due to the coulomb repulsion of the respective alkali ions. The unfolding effect was stronger for linear than branched polymers. However, charge states and degrees of polymerization needed to be high enough for a good separation. De Winter and co-workers could identify a stepwise unfolding process with increasing degree of polymerization.26 In this work, we describe a new and simpler approach to gain information about these types of heterogeneities through online coupling of UPLC in size exclusion mode with ESI-MS. We used SEC for the separation because unlike other separation modes the separation in this mode should solely occur due to the hydrodynamic volume with no interference of other interactions. This should simplify the interpretation, and the above-mentioned heterogeneities should show a slight difference in hydrodynamic volume. The MS gave us access to this information for every single mass (respective m/z value) and hence for each degree of polymerization of the sample. Because these heterogeneities might vary with the molar mass, analysis of the whole MMD-peak (here, the total ion current (TIC)) would not lead to the desired information. On the basis of a variety of examples, we demonstrate the possibilities and limitations of this approach.

hydrodynamic volume at identical molar masses. To overcome this limitation, triple detection can be used for cases were the kind of architectural heterogeneity is known. Accuracy of results, however, is typically only high for highly or regularly branched polymers.5,6 Alternative liquid chromatography separation modes for polymers are liquid adsorption chromatography (LAC), gradient polymer elution chromatography (GPEC), or temperature gradient interaction chromatography (TGIC).7,8 These separation modes are based on enthalpic interactions of the analytes with the stationary phase. The elution pattern of complex samples is usually dominated by overlaying multiple heterogeneities and distributions. Liquid chromatography under critical conditions (LCCC)9 compensates the enthalpic and entropic interactions for a certain monomer or pseudomonomer so that it becomes chromatographically invisible. The elution thus only depends on other factors, for example, the chemical composition distribution (CCD) or functionality type distribution (FTD). For the detection in polymer chromatography, one or more mass or concentration sensitive detectors are still common. A disadvantage of these detectors is the inability to detect single polymer chains rather than bulk distributions in response to a specific detectable variance. That is why mass spectrometric detectors became increasingly popular in recent years.10 The challenge in the applicability of a mass spectrometric detector is the ionization of the polymers. Most polymers are rather nonpolar, and ionization is difficult for higher masses. Also, intact molecular ions need to be formed. Therefore, soft ionization techniques, especially electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI), are widely used.11 While higher masses and less polar polymers can be better analyzed by MALDI, ESI has the advantage to be easily coupled online to a chromatographic system. Among others, this enables the possibility to create reconstructed ion chromatograms (RICs), thus chromatograms of a single mass trace. Another technique, quite recently started to be adopted to polymer analysis, is ion mobility spectrometry (IMS), in almost all cases in combination with mass spectrometry.12 IMS adds another dimension to the analysis by separating ions according to their collision cross section (CCS). The CCS is similar to the hydrodynamic volume, being a measure for the size and shape of an ion in a gas. Despite all efforts in separation and detection, it is not always possible to properly characterize a polymer. Especially heterogeneities in topology or microstructure often as isomers are difficult to analyze. Such heterogeneities stem from the constitution of the polymer chain, branching, isomer end groups, chirality, tacticity, or monomer sequence. In some of these cases, the chromatographic resolution even with UPLC is not sufficient to separate these heterogeneities. The mass spectrometric analysis may fail due to mass isomers or due to a complex matrix. For some few applications, it was possible to overcome these challenges by using MSn methods or 2Dchromatography.13,14,15 Gerber and Radke describe a separation of linear and star shaped polymers by two-dimensional chromatography,16 and Choi and co-workers18 and Schoenmakers co-workers17 reported a separation of branched polymers. Trathnigg and co-workers were able to separate block copolymers by symmetry.19 Other groups tried to overcome these difficulties by using IMS-MS to separate structural/topological isomers. Kim et al.

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EXPERIMENTAL SECTION Materials. Poly(ethylene glycol), poly(ethylene glycol)-bpoly(propylene glycol)-b-poly(ethylene glycol), crown ethers, glycerol ethoxylate, trimethylpropane ethoxylate, and oxoalcohol ethoxylates were obtained from commercial suppliers. Polyglycerines with different degrees of branching were synthesized for us by a cooperation partner.27 We analyzed polyglycerines with 0, 25%, 45%, 60%, and 100% branching. The 100% branched species is a G4 dendrimer. All other samples exhibit a molar mass distribution with mean molar masses between 1000 and 3000 Da, suitable for ESI analysis of single charged ions. Structures of these polymers can be seen in Chart 1. Chromatography. For the chromatographic separation, a UPLC system (Waters GmbH) was used. The system was equipped with an ACQUITY UPLC APC XT 45 (45 Å, 1.7 μm particle size, 4.6 mm × 150 mm) for size exclusion experiments or an ACQUITY BEH C18 Column (130 Å, 1.7 μm particle size, 2.1 mm × 100 mm) for LAC experiments and an ACQUITY UPLC BEH C18 VanGuard Precolumn (130 Å, 1.7 μm, 2.1 mm × 5 mm). The autosampler and column were operated at 25 °C. The SEC experiments were performed with different mobile phases, depending on the samples. Samples 1− 5 were analyzed in 60% ACN and 40% water and polyglycerines (6) as well as samples 7 and 8, in methanol (MeOH). An amount of 0.2% formic acid was added to the mobile phase. The flow rate was 0.25 mL/min. For the isocratic experiments, the samples were dissolved in a solvent mixture corresponding to the mobile phase composition. Two microliters of the samples with a concentration of 0.1 mg/mL was injected. For the oxoalcohol ethoxylates, also LAC experiments in 80% MeOH and 20% water were performed. UPLC/MS B


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between 20 and 40 eV. Argon was used as collision gas. Data were processed using MassLynx 4.1 (Waters).

Chart 1. Structures of the Analyzed Polymers

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RESULTS AND DISCUSSION Our experimental setup allowed the reconstruction of chromatograms only for a single selected m/z from the mass spectra, which display the elution of a single polymer chain and possibly isomeric structures. These reconstructed ion chromatograms (RICs) enabled the analysis of the full width at halfmaximum (fwhm) and retention time of peaks, separately for every degree of polymerization. The hypothesis was that even if isomeric structures could not be separated chromatographically the partial separation must lead to a broadening of the respective peak.28 Other than that, we intended to gain information on whether the fwhm is different for structural isomers in general and about the retention of single polymer chains. The broadening of the chromatographic peaks in this case would not originate from the already well-known band broadening factors in chromatography from diffusion.29−34 This band broadening would be attributed to the nature and composition of the analyte itself. Surprisingly, there is very little investigation into the peak width or peak shape due to the analyte structure itself found in the literature.35−37 The principle of the approach is shown in Figure 1. Linear, Star Shaped, and Cyclic PEGs. Linear PEG 1, block PEG with a middle group of a propylene glycol (PG) 2, three monodisperse crown ethers 3 as cyclic PEG, and two three-arm stars of PEG 4 and 5 with different core groups were analyzed with UPSEC/ESI-MS. When compared to the linear PEG (blue), the PEG with a middle PG group (yellow) revealed higher retention times and therefore a lower hydrodynamic volume in Figure 2. The star polymer with the smaller core (green) displays a higher hydrodynamic volume in comparison with the bigger core one (purple). This could be due to a more rigid structure conditioned by higher repulsive forces between the ethylene oxides. From the progression of the retention times with molar masses, it can be estimated that for higher degrees of polymerization the two curves would converge. A salient point in both graphs at a similar molar mass of about 400 Da is noticeable. Due to the ring tension, the order of elution is inverse for the crown ethers (red). Lower masses have a higher hydrodynamic volume. Considering the overall elution order of the samples, it is likely that the chromatographic mode is not a pure SEC mode. The polarity of the polymer types influences the elution order to an extent although the SEC mode is true for the different degrees of polymerization of each sample. The crown ethers, for example,

grade solvents (TH Geyer, Sigma-Aldrich) were used for chromatography. Mass Spectrometry. A Q-TOF Ultima ESI-TOF mass spectrometer (Micromass) running at 3 kV capillary voltage, at a source temperature of 120 °C and a desolvation temperature of 300 °C, was used for all measurements. The mass spectrometer was operating in the positive ion mode. A solution of 0.05 mg/L sodium trifluoroacetate was added to the eluent from the chromatography via a mixing tee in a flow of 3 μL/min to improve ionization conditions. Tandem mass spectrometry (MS/MS) experiments using collision induced dissociation (CID) were carried out with collision energy

Figure 1. Principle of the approach. C


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Figure 2. Molar mass vs retention time and fwhm vs molar mass for samples 1 to 5. For the crown ethers, 3 monodisperse samples of 12-crown-4, 15-crown-5, and 18-crown-6 were used. All other samples were disperse.

possess no end groups and therefore a lower polarity, resulting in higher retention times on the relatively nonpolar column. Retention times of the two star polymers differ much more from each other than the two linear polymers. Since the core of 4 is more polar than that of 5, this difference may also influence the retention times on the reverse phase column. Considering the fwhms in Figure 2 (right) for these samples, the overall slight decrease of fwhms with increasing molar mass, seen here and in other figures, is due to the diffusion happening in the chromatographic system. Because the retention times decrease with increasing molar mass, longitudinal diffusion processes for lower molar mass polymers are higher. Also, because of the ability to enter more/smaller pores, the Eddy diffusion is higher for smaller polymer chains. Two curves stick out of the otherwise quite uniform progressions. The cyclic PEO structures show a higher fwhm than the other species. The order here is not inversed in comparison with the elution order. An explanation might be that the conformation of the rings can vary more than in the other structures. Different conformer isomers possess different hydrodynamic volumes. The existence of several conformers next to each other might lead to the peak broadening. Due to the higher ring tensions, the conformer isomers of the smallest ring differ more from each other than for larger rings. The glycerol-core star displays an increasing fwhm between 250 and 500 Da. To investigate this and the distinctive feature in retention times further, the RICs for all degrees of polymerization between 250 and 500 Da for both star polymers are shown in Figure 3. Figure 3 illustrates that for sample 4 the peak indeed is getting wider between 250 and 500 Da. Also, the shift to lower retention times from degree of polymerization of 6 is visible. For sample 5, the shift is due to the appearance of a second peak that becomes the most intense peak from degree of polymerization of >6, while the former most intense peak has almost disappeared at a degree of polymerization of 10. Not surprisingly, the fwhm does not increase in this case. The software script (Origin 2016) used to calculate the fwhm could distinguish between these peaks. An explanation for the peak broadening of 4 and existence of two peaks for 5 might be that, for lower degrees of polymerization, the polymer chains are more linear, despite

Figure 3. Reconstructed ion chromatograms for sample 4 (left) and sample 5 (right) for three of their degrees of polymerization between m/z 250 and 600.

the possibility of three arms. Only two of the three arms are occupied. As the degree of polymerization increases, the polymer chains become more star shaped and the third arm begins to grow as well. For an interim molar mass range (250− 500 Da), the two and three arm species exist next to each other, resulting in a broader peak for 4 and two partially separated peaks for 5. To confirm this, Figure 4 shows CID MSMS spectra of the two marked areas of the polymer 5 with 6 EO units total, marked in Figure 3. In Figure 4, series of peaks differing by 44 Da (one EO monomer) are marked in the same color. The red series is most likely attributable to a dissociated (EO)x arm. In the right spectrum, dissociated arms with up to six EO units are present. In the left spectrum, only up to five are present. Also, the intensity here is shifted toward a shorter arm length, confirming the assumption above. The green, blue, and yellow series must originate from fragments with a (partly) intact core. Possible dissociation pathways are illustrated in Scheme 1. We propose that the green series corresponds to a fragment of the core with one arm occupied with different numbers of EOs and the blue series corresponds to two and the yellow to three occupied arms. This coincides with the hypothesis above as the yellow series is only present in the left spectrum and the green is most intense in the right. The left spectrum indicates more but shorter arms, while the right spectrum, of the peak only present for lower degrees of polymerization, indicates less but longer arms. D


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Figure 4. CID-MSMS spectra for the first (left) and second (right) marked retention regions of a polymerization degree of 6 of sample 5 in Figure 3.

the degree of branching on the hydrodynamic volume cannot be observed. However, the fwhms show significant differences. The decrease of the fwhm with higher molar masses is comparable to that of the other polymer samples. In addition, the fwhm increases with the degree of branching. The reason for this is likely to be the dispersity in the structure of the polymer chains. Chains with the same molar mass and the same degree of branching can have a dispersity in the sites where these branching points are located. This dispersity follows the band broadening due to slightly different retention times. Further, the more branched the structures, the higher is the diffusion. From these considerations follows that a mixture of isomeric polyglycerines with different degrees of branching must also lead to an increase in fwhm. Since the 100% branched species is a dendrimer and the 0% branched species contain different end groups from synthesis, this was analyzed with the 25%, 45%, and 60% branched samples. In Figure 6, every two as well as three samples were mixed in equal parts. It can be seen that for every possible combination the fwhm of the mixture is higher than for the respective samples. Similar to Figure 5, the retention times did not differ significantly from each other (not shown). Since the values of the fwhms and retention times fluctuate due to different dwell times and possibly a small amount due to the mass spectrometer itself, the mean retention times for the disperse samples between m/z 500 and 1500 are shown in Figure 7 (left). Here, the mean fwhms for all sample and mixtures are shown too. For the mean values, the increase in retention time with degree of branching is visible, but the values differ only between 5.420 and 5.428 min. The difference in FWMH on the contrary is larger. Measurement of the fwhm of an unknown polyglycerine sample could lead to information on the extent of branching in the sample. One possibility that cannot be accounted for with this method is, e.g., the distinction between a degree of branching of 50% or a mixture between 25% and 60% that leads to the same fwhm due to the dispersity in branching. Oxoalcohol Ethoxylates. Isomeric samples 7 and 8 were analyzed by UPSEC/ESI-MS as well. The structure for sample 8 in Chart 1 is only one possible structure. The manufacturer states a mean degree of branching in the alkyl part of 2.8. In

Scheme 1. Precursor Ion (Grey) and Proposed Dissociation Patternsa

a

All species varying by dissociation of EOs are marked in the same color.

Polyglycerines with Different Degrees of Branching. Polyglycerines (6) can be branched due to their three active sites. Since a chain growth or the number of arms makes no difference in molar mass, the species cannot be differentiated by mass spectrometry. Disperse samples with a degree of branching of 0, 25%, 45%, and 60% and a G4 dendrimer (100% branching) were analyzed as mentioned above. In Figure 5, the molar masses and corresponding fwhms are given. In comparison with the butyl methacrylates or PEG polymers, the differences in the retention times are very small. An influence of E


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Figure 5. Molar mass vs retention time and fwhm vs molar mass for polyglycerines containing degrees of branching of 0, 25%, 45%, 60%, and 100%. 100% branched was a monodisperse dendrimer; all other samples were disperse.

increase can be seen. The effect thereby is larger in the low molar mass region. This is due to the larger influence of the alkyl group on the whole polymer for smaller chains. Similar to the polyglycerines, the mean values for the retention times and fwhms were calculated for a molar mass range. The values were compared for mixtures of both samples with various amounts, as can be seen in Figure 9. The band broadening reaches a maximum at 45% of 7. This could be expected, taking into account the theoretical peak width of merging Gaussian peaks at low distances.28 Two overlapping peaks of similar intensity (here at 45% of 7) lead to a higher band broadening than a higher and lower intense peak at the same distance (here at lower or higher relative amounts of 7). The retention time increases with an increased amount of sample 7. This increase, however, does not contain information about the dispersity of the branching. It could also originate from a structural change when applied to an unknown sample. Only in combination with the increase in fwhm can a branching dispersity increase be validated. For an unknown sample, this could lead to information about the dispersity in branching and possibly other heterogeneities just by a single chromatographic run. To confirm that the band broadening originates from a dispersity in branching and to explain the difference in fwhm between samples 7 and 8, LAC/ESI-MS experiments were performed. By taking the structures of both samples and possible isomers of sample 8 into account, the fwhms are assumed to differ more than observed in Figures 8 and 9. Since the separation power in SEC is limited, which only enabled the analysis of fwhms of not completely separated peaks in the first place, the separation power in LAC mode should be larger. In adsorption chromatography, the structural isomers were investigated in more detail. Figure 10 (top) shows the RIC exemplary for a polymerization degree of 12 for both samples. For sample 7, two peak maxima are shown. This was unexpected, taking the linear structure of the molecule into account. The existence of two isomers for 7 can be explained by one possible isomerization during synthesis. For 7, ethene and, for 8, ethene and propene were converted to α-olefins by the Shell higher olefin process (SHOP).38,39 In an intermediate step, α-olefins were oxidized to aldehydes in a hydro-

Figure 6. fwhm vs molar mass graphs of the three isomeric branched polyglycerine samples in different combinations and respective equal part mixtures of them.

Figure 7. Retention time vs degree of branching for branched polyglycerines derived from the mean values between m/z 500 and 1500 (left) and fwhms for the polyglycerines and equal part mixtures of them derived from mean values between m/z 500 and 1500 (right).

Figure 8, the retention times and fwhms vs molar masses are shown. The retention times differ slightly, and the retention time of the mixture is between both samples. The fwhms for sample 8 are slightly higher, probably due to isomeric structures of the branched alkyl end group. For the 1:1 mixture, a distinct F


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Figure 8. Molar mass vs retention time and fwhm vs molar mass for samples 7 and 8 and a mixture of them.

Furthermore, the possibility to replace the SEC separation by an ion mobility separation, due to the similar separation mechanisms but shorter analysis time, was investigated. The resolution of the ion mobility separation was lower than in SEC and not high enough for an analysis of the fwhms (Figures S-3 and S-4 for samples 7 and 8)

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CONCLUSION ESI mass spectrometry can offer more than an access to mass dependent information like MMD, end group masses, or CCD in polymer analysis. Coupled online to a chromatographic system, the analysis of reconstructed ion chromatograms has the potential to lead to information that is otherwise inaccessible or accessible only by time-consuming or expensive methods. By investigating the retention times and fwhms of single degrees of polymerization, it was possible to obtain information on small heterogeneities in microstructure or topology even if there is no expected or assumed heterogeneity. The separation system could be a simple and fast SEC. For polymer heterogeneities that could not be resolved chromatographically, information on branching or the shape of the polymer chains could be obtained. If samples of known microstructure, for example, branching, are available, it is possible to gain information on the structure of unknown samples. The retention times of RICs lead to the average degree of branching, and fwhms lead to the branching distribution. This approach could potentially be used in production control of oligomeric products or other routinely done analyses to quickly indicate deviations from set parameters. For a further investigation into the nature of a deviation, results can be compared to standards of possible heterogeneities.

Figure 9. Mean retention time vs 7 [%] and fwhm vs 7 [%] for different mixtures of samples 7 and 8 in the range of m/z 500−1250.

Figure 10. Reconstructed ion chromatograms of LAC/ESI-MS measurements for a polymerization degree of 12 for samples 7 and 8.

formylation. In this step, both aldehydes and iso-aldehydes are formed, which resulted in the two isomers of 7. After reduction to alcohols, a reaction with ethylene oxide in several steps lead to the final products. As expected, sample 8 shows greater variety of isomers due to the distribution in branching. Up to six peak maxima could be detected. Additional Experiments. It was found that the method used in this work to characterize the microstructure of polymers can only be utilized for small heterogeneities that cannot be separated chromatographically. If the structural differences of isomers are large enough, e.g., the heterogeneity is present in every monomer unit, the band broadening of RICs turns into a peak with two maxima. Hence, the fwhm cannot be calculated. This was the case for isomeric polymers poly(n-butyl methacrylate) and poly(t-butyl methacrylate) (Figures S-1 and S-2).

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.7b05214. Figures S-1 and S-2: results of the analyses of poly(nbutyl methacrylate) and poly(t-butyl methacrylate); G


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(25) Trimpin, S.; Plasencia, M.; Isailovic, D.; Clemmer, D. E. Anal. Chem. 2007, 79, 7965−7974. (26) Duez, Q.; Josse, T.; Lemaur, V.; Chirot, F.; Choi, C. M.; Dubois, P.; Dugourd, P.; Cornil, J.; Gerbaux, P.; De Winter, J. J. Mass Spectrom. 2017, 52, 133−138. (27) Paulus, F.; Schulze, R.; Steinhilber, D.; Zieringer, M.; Steinke, I.; Welker, P.; Licha, K.; Wedepohl, S.; Dernedde, J.; Haag, R. Macromol. Biosci. 2014, 14, 643−654. (28) Delley, R. Chromatographia 1984, 18, 374−382. (29) Popovici, S.-T.; Kok, W. T.; Schoenmakers, P. J. J. Chromatogr. A 2004, 1060, 237−252. (30) Hagel, L. J. Chromatogr. 1985, 324, 422−427. (31) Farkas, T.; Guiochon, G. Anal. Chem. 1997, 69, 4592−4600. (32) Felinger, A.; Pasti, L.; Dondi, F.; van Hulst, M.; Schoenmakers, P. J.; Martin, M. Anal. Chem. 2005, 77, 3138−3148. (33) Giddings, J. C.; Bowman, L. M.; Myers, M. N. Macromolecules 1977, 10, 443−449. (34) Busnel, J. P.; Foucault, F.; Denis, L.; Lee, W.; Chang, T. J. Chromatogr. A 2001, 930, 61−71. (35) Weis, D. D.; Wales, T. E.; Engen, J. R.; Hotchko, M.; Ten Eyck, L. F. J. Am. Soc. Mass Spectrom. 2006, 17, 1498−1509. (36) Gemperline, P. J. J. Chem. Inf. Model. 1984, 24, 206−212. (37) Mott, S. D.; Grushka, E. J. Chromatogr. 1976, 126, 191−204. (38) Vogt, D. In Aqueous-Phase Organometallic Catalysis; John Wiley & Sons: New York, 1998; pp 541−547. (39) Klug, P.; Lindner, T.; Loeffler, M.; Fischer, D.; Kunze, M.; Mildner, C.; Vasco, S. L.; Cerny, T. Cationic Comb Copolymers, Preparation Therof And Use Thereof in Cosmetic, Pharmaceutical And Dermatological Formulations. Google Patents, 2012.

Figures S-3 and S-4 results of the IMS-MS measurements of samples 7 and 8 (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Phone: +493081041632. Fax: +493081041137. ORCID

Jana Falkenhagen: 0000-0001-7772-606X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Dr. Florian Paulus and Prof. Rainer Haag from FU Berlin for providing us with samples of branched polyglycerines. We also thank Dr. Artjom Döring, Marie-Theres Picker, and Prof. Dirk Kuckling from the University of Paderborn for providing us with measurement time on their UPLC-IMS instrument.

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