Use of Pulsed Gradient Spin−Echo NMR as a Tool in MALDI Method Development for Polymer Molecular Weight Determination

Mazarin, Michaël; Viel, Stéphane; Allard-Breton, Béatrice; Thevand, André; Charles, Laurence

doi:10.1021/ac0522207

Cited by 29 publications

(26 citation statements)

References 38 publications

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“…Underestimation of M w parameters is commonly reported for PMAA in both positive and negative mode MALDI [32]. However, relative deviations were quite low, with a maximal value of 15% for the smallest polymer and lying in the 4%-12% range for other samples, which is consistent with results obtained in a previous study [24]. The same methylation protocol was then applied to the MAA-MMA samples to transform these amphiphilic copolymers, for which no interpretable signal could be obtained in MALDI as illustrated in Figure 2a, into PMMA homopolymers more amenable to this ionization technique.…”

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confidence: 91%

“…Typically, these scaling parameters are obtained by analyzing a series of monodisperse polymer standards under a given set of experimental conditions. The corresponding procedure has already been thoroughly described in other published works [24,25] and will only be briefly described here. The PGSE diffusion decays are analyzed using a nonlinear least squared fitting (based on the Levenberg-Marquardt algorithm), which allows the diffusion coefficients to be obtained by taking the diffusion time and gradient pulse duration as input parameters.…”

Section: Nuclear Magnetic Resonancementioning

confidence: 99%

“…As a result, a multiple detection configuration is usually required to reach reliable molecular weight data by SEC, since the intensity of the response obtained in each detection mode does not only depend on molecular weight but also on parameters that are a function of the macromolecule composition [16,17]. Pulsed gradient spin echo (PGSE) [18 -20] NMR can be used to estimate the weight average molecular weight (M w ) of a synthetic homopolymer from the measurement of its molecular self-diffusion coefficient [21][22][23][24]. For block copolymers, we have recently shown that such estimation not only requires properly recorded calibration curves for each of the polymers constituting the blocks, but also a hydrodynamic model to correctly interpret the diffusion data [25].…”

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confidence: 99%

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Analytical strategy for the molecular weight determination of random copolymers of poly(methyl methacrylate) and poly(methacrylic acid)

Giordanengo

Viel

Hidalgo

et al. 2010

J. Am. Soc. Mass Spectrom.

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Molecular weight characterization of random amphiphilic copolymers currently represents an analytical challenge. In particular, molecules composed of methacrylic acid (MAA) and methyl methacrylate (MMA) as the repeat units raise issues in commonly used techniques. The present study shows that when random copolymers cannot be properly ionized by MALDI, and hence detected and measured in MS, one possible analytical strategy is to transform them into homopolymers, which are more amenable to this ionization technique. Then, by combining the molecular weight of the so-obtained homopolymers, as measured by MS, with the relative molar proportion of the MMA and MMA units, as given by 1 H NMR spectrum, one can straightforwardly estimate the molecular weight of the initial copolymer. A methylation reaction was performed to transform MAA-MMA copolymer samples into PMMA homopolymers, using trimethylsilyldiazomethane as a derivatization agent. Weight average molecular weight (M w ) parameters of the MAA-MMA copolymers could then be derived from M w values obtained for the methylated MAA-MMA molecules by MALDI, which were also validated by pulsed gradient spin echo (PGSE) NMR. An alkene function in one of the studied copolymer end-groups was also shown to react with the methylation agent, giving rise to MMA-like polymeric by-products characterized by tandem mass spectrometry and which could be avoided by adjusting the amount of the trimethylsilyldiazomethane in the reaction medium. (J Am Soc Mass Spectrom 2010, 21, 1075-1085) © 2010 American Society for Mass Spectrometry P olymers based on weak acids such as poly-(methacrylic acid) (PMAA) have attracted considerable attention because of the ability of the system to change strongly upon variations in the pH and ionic strength of the solution [1]. For example, amphiphilic PMAA-based block copolymers were reported to efficiently adsorb uranyl ions [2] or to selfassemble to produce dynamic micelles sensitive to different stimuli [3][4][5][6]. In particular, block copolymers containing PMAA and poly(methyl methacrylate) (PMMA) segments were the subject of intensive research activities [7][8][9][10]. However, interesting properties were also demonstrated for copolymers containing random MAA-MMA segments [11][12][13][14]. Performance of such materials highly depends on structurally-related parameters but also on molecular weight distribution.Determination of molecular weight parameters is not a trivial task for copolymers. Liquid state nuclear magnetic resonance (NMR) is the most commonly used technique for this purpose but only allows the number average molecular weight (M n ) parameter to be obtained. Size exclusion chromatography (SEC) requires calibration with narrow standards of the same chemical nature and structure as the analyte. Alternatively, one can use calibration which relies on Mark-HouwinkKuhn-Sakurada (MHKS) parameters being known for the standards and the analyte [15], since these parameters depend on both the nature of co-monomers and their relative proportion with...

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confidence: 91%

Section: Nuclear Magnetic Resonancementioning

confidence: 99%

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confidence: 99%

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Analytical strategy for the molecular weight determination of random copolymers of poly(methyl methacrylate) and poly(methacrylic acid)

Giordanengo

Viel

Hidalgo

et al. 2010

J. Am. Soc. Mass Spectrom.

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“…However, the scaling parameters of Eq. (1) specific to that polymersolvent system must be found by measuring ⟨D⟩ on fractionated samples of the polymer with known M. Therefore, currently all PGSE NMR-based methods which convert from D to M cannot independently measure the absolute molecular mass distribution [12,13,14,15,16,17,18,19,20,21,22,23,24,25].In this paper we show that ν in Eq.(1) can be directly estimated from a single PGSE experiment in which the extremity (end-group) polymer signal can be spectrally resolved by a chemical shift from the polymer main-chain signal. The scaling exponent, ν, is a measure of the polymer conformation as well as solvent quality [3,26], with bounds of ν = 1/3 for a perfectly coiled, impenetrable, polymer ball and ν = 1 for a perfectly straight polymer rod [17].…”

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Scaling exponent and dispersity of polymers in solution by diffusion NMR

Williamson

Röding

Miklavcic

et al. 2017

Journal of Colloid and Interface Science

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Molecular mass distribution measurements by pulsed gradient spin echo nuclear magnetic resonance (PGSE NMR) spectroscopy currently require prior knowledge of scaling parameters to convert from polymer self-diffusion coefficient to molecular mass. Reversing the problem, we utilize the scaling relation as prior knowledge to uncover the scaling exponent from within the PGSE data. Thus, the scaling exponent-a measure of polymer conformation and solvent quality-and the dispersity (M w /M n ) are obtainable from one simple PGSE experiment. The method utilizes constraints and parametric distribution models in a two-step fitting routine involving first the mass-weighted signal and second the number-weighted signal. The method is developed using lognormal and gamma distribution models and tested on experimental PGSE attenuation of the terminal methylene signal and on the sum of all methylene signals of polyethylene glycol in D 2 O. Scaling exponent and dispersity estimates agree with known values in the majority of instances, leading to the potential application of the method to polymers for which characterization is not possible with alternative techniques. Keywords:Pulsed gradient spin echo, pulsed field gradient, Nuclear Magnetic Resonance spectroscopy, Molecular weight distribution, Polymers, DOSY, Polydispersity Index, Self-diffusion, Molar mass, Flory exponent, Lognormal distribution, Gamma distribution, End-group analysis, Scaling law Synthetic polymers have distributions of molecular masses determined by their synthesis [1]. Measuring the molecular mass distribution rather than its average is important because the dispersity can influence polymer properties [2]. Absolute as opposed to relative measurements are needed when using polymer physics to fully realize the potential applications of a polymer [3]. Only a handful of techniques can measure the absolute molecular mass distribution [3]. The gold standard is size exclusion chromatography (SEC) using universal calibration [4], which does not always work [5,6]. New techniques must be developed to aid in the advancement of polymer science.Pulsed gradient spin echo nuclear magnetic resonance (PGSE NMR) [7,8] is a powerful technique for obtaining the distribution of polymer self-diffusion coefficients D [9], from which the distribution of molecular masses M can be obtained by the scaling law [10] ration give PGSE NMR a competitive edge with respect to SEC. Chemical shift information [7], e.g. in a diffusion ordered spectroscopy (DOSY) plot [11], provides the ability to observe chemical heterogeneity and impurity. Sample preparation generally does not require filtration because contaminates from large particles such as dust do not impact the experiment. However, the scaling parameters of Eq. (1) specific to that polymersolvent system must be found by measuring ⟨D⟩ on fractionated samples of the polymer with known M. Therefore, currently all PGSE NMR-based methods which convert from D to M cannot independently measure the absolute molecular mass distribution [...

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“…To sequence the peptide, the molecular ion is fragmented by post-source decay (PSD; for peptides <1,500 Da) or ion-source decay (ISD; for peptides >1,500 Da) and the sequence is determined from the mass of fragmented ions (72). Size exclusion chromatography combined with MALDI mass spectrometry (SEC/MALDI) (73) or pulsed gradient spin-echo (PGSE) NMR combined with MALDI can be used to determine molecular weight distribution of macromers and polymers with very high accuracy (74). Accurate determination of macromer molecular weight distribution and sequence distribution of the conjugated peptide is required for relating the chemical/molecular structure to conformation and nanostructure of the selfassembled polymer-peptide conjugate (75).…”

Section: Characterization Of Peptidomimetic Npsmentioning

confidence: 99%

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

Jabbari

2008

Pharm Res

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Peptides produce specific nanostructures, making them useful for targeting in biological systems but they have low bioavailability, potential immunogenicity and poor metabolic stability. Peptidomimetic self-assembled NPs can possess biological recognition motifs as well as providing desired engineering properties. Inorganic NPs, coated with self-assembled macromers for stability and anti-fouling, and conjugated with target-specific ligands, are advancing imaging from the anatomy-based level to the molecular level. Ligand conjugated NPs are attractive for cell-selective tumor drug delivery, since this process has high transport capacity as well as ligand dependent cell specificity. Peptidomimetic NPs can provide stronger interaction with surface receptors on tumor cells, resulting in higher uptake and reduced drug resistance. Self-assembled NPs conjugated with peptidomimetic antigens are ideal for sustained presentation of vaccine antigens to dendritic cells and subsequent activation of T cell mediated adaptive immune response. Self-assembled NPs are a viable alternative to encapsulation for sustained delivery of proteins in tissue engineering. Cell penetrating peptides conjugated to NPs are used as intracellular delivery vectors for gene expression and as transfection agents for plasmid delivery. In this work, synthesis, characterization, properties, immunogenicity, and medical applications of peptidomimetic NPs in imaging, tumor delivery, vaccination, tissue engineering, and intracellular delivery are reviewed.

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Use of Pulsed Gradient Spin−Echo NMR as a Tool in MALDI Method Development for Polymer Molecular Weight Determination

Cited by 29 publications

References 38 publications

Analytical strategy for the molecular weight determination of random copolymers of poly(methyl methacrylate) and poly(methacrylic acid)

Analytical strategy for the molecular weight determination of random copolymers of poly(methyl methacrylate) and poly(methacrylic acid)

Scaling exponent and dispersity of polymers in solution by diffusion NMR

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

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