Diffusion-ordered Spectroscopy Research Articles

Automated component analysis in DOSY NMR using information criteria

This study introduces a model selection technique based on Bayesian information criteria for estimating the number of components in a mixture during Diffusion-Ordered Spectroscopy (DOSY) Nuclear Magnetic Resonance (NMR) data analysis. As the accuracy of this technique is dependent on the efficiency of parameter estimators, we further investigate the performance of the Weighted Least Squares (WLS) and Maximum a Posteriori (MAP) estimators. The WLS method, enhanced with meticulously tuned L2-regularization, effectively detects components when the difference in self-diffusion coefficients is more than two-fold, especially when the component with the smaller coefficient has a larger weight ratio. The MAP method, strengthened by a substantial database of prior information, exhibits outstanding precision, decreasing this threshold to 1.5 times. Both estimators provide weight ratio estimates with standard deviations of approximately around 1 percentage point, although the MAP method tends to overestimate the component with a larger self-diffusion coefficient. Deviations from the expected values can exceed 10 percentage points, often due to inaccuracies in component detection. The error estimates are determined using data resampling techniques derived from a large-scale 1000-point experiment and an additional five measurements from a single-component mixture. This approach allowed us to thoroughly examine data distribution characteristics, thereby laying a robust groundwork for future refinement efforts.

Recycled PLA for 3D Printing: A Comparison of Recycled PLA Filaments from Waste of Different Origins after Repeated Cycles of Extrusion.

The objective of this work is to evaluate the reprocessing of PLA 3D printing waste from different origins, into filaments and films, and without the addition of any additive. Two types of waste were considered: a blend of different printing wastes (masks, visors, other components) of personal protective equipment coming from an association of Spanish coronamakers, and PLA waste from a single known commercial source. Both types of materials were subjected to repeated extrusion cycles and processed into films by compression molding. Samples were characterized after each cycle and their mechanical and viscosity properties evaluated. Diffusion-ordered NMR spectroscopy (DOSY) experiments were also carried out to estimate molecular weights. The results show a better performance for the PLA waste from the known origin, capable of withstanding up to three re-extrusion cycles per two for the waste blending, without significant degradation. Additionally, a model to address collection and mechanical recycling cycles under two different scenarios (full traceability and not full traceability) was proposed.

Raman Diffusion-Ordered Spectroscopy.

The Stokes-Einstein relation, which relates the diffusion coefficient of a molecule to its hydrodynamic radius, is commonly used to determine molecular sizes in chemical analysis methods. Here, we combine the size sensitivity of such diffusion-based methods with the structure sensitivity of Raman spectroscopy by performing Raman diffusion-ordered spectroscopy (Raman-DOSY). The core of the Raman-DOSY setup is a flow cell with a Y-shaped channel containing two inlets: one for the sample solution and one for the pure solvent. The two liquids are injected at the same flow rate, giving rise to two parallel laminar flows in the channel. After the flow stops, the solute molecules diffuse from the solution-filled half of the channel into the solvent-filled half at a rate determined by their hydrodynamic radius. The arrival of the solute molecules in the solvent-filled half of the channel is recorded in a spectrally resolved manner by Raman microspectroscopy. From the time series of Raman spectra, a two-dimensional Raman-DOSY spectrum is obtained, which has the Raman frequency on one axis and the diffusion coefficient (or equivalently, hydrodynamic radius) on the other. In this way, Raman-DOSY spectrally resolves overlapping Raman peaks arising from molecules of different sizes. We demonstrate Raman-DOSY on samples containing up to three compounds and derive the diffusion coefficients of small molecules, proteins, and supramolecules (micelles), illustrating the versatility of Raman-DOSY. Raman-DOSY is label-free and does not require deuterated solvents and can thus be applied to samples and matrices that might be difficult to investigate with other diffusion-based spectroscopy methods.

Using surface plasmon resonance, capillary electrophoresis and diffusion-ordered NMR spectroscopy to study drug release kinetics

Nanomedicines, including polymer nanocarriers with controlled drug release, are considered next-generation therapeutics with advanced therapeutic properties and reduced side effects. To develop safe and efficient nanomedicines, it is crucial to precisely determine the drug release kinetics. Herein, we present application of analytical methods, i.e., surface plasmon resonance biosensor technology (SPR), capillary electrophoresis, and 1H diffusion-ordered nuclear magnetic resonance spectroscopy, which were innovatively applied for drug release determination. The methods were optimised to quantify the pH-triggered release of three structurally different drugs from a polymer carrier. The suitability of these methods for drug release characterisation was evaluated and compared using several parameters including applicability for diverse samples, the biological relevance of the experimental setup, method complexity, and the analysis outcome. The SPR method was the most universal method for the evaluation of diverse drug molecule release allowing continuous observation in the flow-through setting and requiring a small amount of sample.

Accounting for gradient non-uniformity in spatially-encoded diffusion-ordered NMR spectroscopy

Diffusion-ordered NMR spectroscopy (DOSY) is a powerful tool for the analysis of mixtures. Spatially-encoded (SPEN) DOSY makes it possible to collect a complete DOSY data set in a single scan, through spatial parallelisation of the gradient dimension. One limitation of current SPEN DOSY experiments is that the data is analysed assuming that the field gradient is uniform over the sample. This is usually not the case for high resolution NMR probes, and even less for triple-axis gradient probes. In this work, we have developed methods to account for gradient non-uniformity in the processing of SPEN DOSY experiment. We have first mapped the field gradient, using a stimulated echo (STE) NMR sequence with a weak readout gradient. We have then modified the calculation of the position-dependent effective gradient pulse area that is used in the analysis of SPEN DOSY data. The resulting model was validated through numerical simulations. A comparison of results obtained with and without inclusion of the effect of non-uniform gradients shows that the proposed approach increases the accuracy of SPEN DOSY experiments.

Synthesis of 177Lu-Labeled, Somatostatin-2 Receptor-Targeted Metalla-Assemblies: Challenges in the Design of Supramolecular Radiotherapeutics.

Self-assembled supramolecular coordination complexes (SCCs) hold promise for biomedical applications in cancer therapy, although their potential in the field of nuclear medicine is still substantially unexplored. Therefore, in this study an exo-functionalized cationic [Pd2L2]4+ metallacycle (L = 3,5-bis(3-ethynylpyridine)phenyl), targeted to the somatostatin-2 receptor (sst2R) and featuring the DOTA chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) in order to bind the β-- and γ-emitter lutetium-177, was synthesized by self-assembly following ligand synthesis via standard solid-phase peptide synthesis (SPPS). This metallacycle was then characterized by reverse-phase high-performance liquid chromatography (RP-HPLC), electrospray ionization mass spectrometry (ESI-MS), and 1H and 1H-DOSY NMR (DOSY = diffusion-ordered spectroscopy). A procedure for the radiolabeling of the metallacycle with 177Lu was also optimized. The resulting [nat/177Lu]Lu-DOTA-metallacycle, termed [nat/177Lu]Lu-Cy, was evaluated concerning its stability and in vitro properties. The compound was more lipophilic compared to the reference [177Lu]Lu-DOTA-TATE (logPOct/H2O = -0.85 ± 0.10 versus -3.67 ± 0.04, respectively). While [natLu]Lu-Cy revealed low stability in a DMEM/F12 GlutaMax medium, it demonstrated good stability in other aqueous media as well as in DMSO. A high sst2R binding affinity (expressed as IC50) was determined in CHOsst2 cells (Chinese hamster ovary cells that were stably transfected with human sst2R). Moreover, the metallacycle exhibited high human serum albumin binding, as assessed by high-performance affinity chromatography (HPAC), and moderate stability in human serum compared to [177Lu]Lu-DOTA-TATE (TATE = (Tyr3)-octreotate). In order to improve stability, a heteroleptic approach was used to develop a less sterically hindered cage-like SCC that is potentially endowed with host-guest chemistry capability, which has been preliminarily characterized by RP-HPLC and ESI-MS. Overall, our initial results encourage future studies on sst2R-directed SCCs and have led to new insights into the chemistry of ss2R-directed SCCs for radiopharmaceutical applications.

Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques.

Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains (Pc1). 1H NMR spectroscopy combined with UV-vis absorption and fluorescence spectroscopy revealed that Pc1 exists as a mixture of regioisomers in monomeric form in dimethyl sulfoxide but forms dimers in an aqueous buffer. PVP, polyethylene glycol castor oil (Kolliphor RH40), and three different triblock copolymers with varying proportions of polyethylene and polypropylene glycol units (termed P188, P84, and F127) were tested as micellar carriers for Pc1. 1H NMR chemical shift analysis, diffusion-ordered spectroscopy, and 2D nuclear Overhauser enhancement spectroscopy was applied to monitor the encapsulation and localization of Pc1 at the polymer interface. Kolliphor RH40 and F127 micelles exhibited the highest affinity for encapsulating Pc1 in the micellar core and resulted in intense Pc1 fluorescence emission as well as efficient singlet oxygen formation along with PVP. Among the triblock copolymers, efficiency in binding and dimer dissolution decreased in the order F127 > P84 > P188. PVP was a strong binder for Pc1. However, Pc1 molecules are rather surface-attached and exist as monomer and dimer mixtures. The results demonstrate that NMR combined with optical spectroscopy offer powerful tools to assess parameters like drug binding, localization sites, and dynamic properties that play key roles in achieving high host-guest compatibility. With the corresponding adjustments, polymeric micelles can offer simple and easily accessible drug delivery systems optimizing phthalocyanines' properties as efficient photosensitizers.

Mechanistic Investigations of Phenoxyimine-Cobalt(II)-Catalyzed C(sp2)-C(sp3) Suzuki-Miyaura Cross-Coupling.

The mechanism of phenoxyimine (FI)-cobalt-catalyzed C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling was studied using a combination of kinetic measurements and catalytic and stoichiometric experiments. A series of dimeric (FI)cobalt(II) bromide complexes, [(4-CF3PhFI)CoBr]2, [(4-OMePhFI)CoBr]2, and [(2,6-diiPrPhFI)CoBr]2, were isolated and characterized by 1H and 19F NMR spectroscopies, solution and solid-state magnetic susceptibility, electron paramagnetic resonance (EPR) spectroscopy, X-ray crystallography, and diffusion-ordered NMR spectroscopy (DOSY). One complex, [(4-CF3PhFI)CoBr]2, was explored as a single-component precatalyst for C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling. Addition of potassium methoxide to [(4-CF3PhFI)CoBr]2 generated the corresponding (FI)cobalt(II) methoxide complex as determined by 1H and 19F NMR and EPR spectroscopies. These spectroscopic signatures were used to identify this compound as the resting state during catalytic C(sp2)-C(sp3) coupling. Variable time normalization analysis (VTNA) of in situ catalytic 19F NMR spectroscopic data was used to establish an experimental rate law that was first-order in a (FI)cobalt(II) precatalyst, zeroth-order in the alkyl halide, and first-order in an activated potassium methoxide-aryl boronate complex. These findings are consistent with turnover-limiting transmetalation that occurs prior to activation of the alkyl bromide electrophile. The involvement of boronate intermediates in transmetalation was corroborated by Hammett studies of electronically differentiated aryl boronic esters. Together, a cobalt(II)/cobalt(III) catalytic cycle was proposed that proceeds through a "boronate"-type mechanism.

Destabilization of water-in-crude oil emulsions using naphthenic acids

Naphthenic Acids (NAs) are widely believed to universally act in a stabilizing capacity during the formation of water-in-crude oil emulsions. This work provides evidence to the contrary wherein differences between commercially acquired NAs and those extracted from crude exhibit opposing effects on emulsion stability. Addition of the commercial NAs to a crude oil prior to water-in-oil emulsion formation resulted in an increase in emulsion destabilization rate. This was demonstrated via quantification of water droplet coalescence using pulsed field gradient nuclear magnetic resonance (NMR) and, over long timescales in the visual observation of the disengagement of a free water phase. The efficacy of the commercial NAs to act in such a demulsification capacity was shown to be effective at concentrations as low as 0.5v/v% and in the presence of saline water of up to 3.5 wt% NaCl. Differences in NA demulsifying ability was observed between three crude oils of various origins with some demonstrating clear visual phase separation whilst others remained in an emulsified state. Conversely, addition of NAs extracted from a crude oil at similar concentrations had negligible effect on the rate of emulsion destabilization. Comparative characterization of the commercial and indigenous NAs was performed using 1H NMR, Diffusion Ordered Spectroscopy (DOSY), Rheometry, Pendant Drop Tensiometry, and Gas Chromatography–Mass Spectrometry. The results of this characterization indicated that differences in emulsion stability were governed not by differences in the reduction of emulsion droplet interfacial tension (IFT) but by the kinetics of molecular diffusion of the NAs during both the emulsification and destabilization phases.

NMR Spectroscopy Study of the Effect of the Molecular Mass of Hypromellose Phthalate on Its Solubility

Scientific relevance. Hypromellose phthalate is used in enteric coatings for oral medicinal products. The proportion of phthalate groups in the polymer is standardised because it has a significant effect on solubility. Whereas, the molecular mass of hypromellose phthalate is not controlled, and its impact on solubility in media with different pH values is understudied.Aim. The study aimed to employ NMR spectroscopy to investigate the effect the molecular mass of hypromellose phthalate may have on the dissolution kinetics at the pH value declared by the polymer manufacturer.Materials and methods. The study analysed hypromellose phthalate isolated from proton-pump inhibitor enteric coatings and the hypromellose phthalate reference standard. The molecular mass of the polymer was estimated by diffusion-ordered NMR spectroscopy (DOSY) with polyethylene glycols of known molecular masses for calibration. The authors studied the dissolution profiles of hypromellose phthalates of different molecular masses using 1H NMR spectra.Results. The authors developed a procedure for estimating the average molecular mass of hypromellose phthalate by DOSY. The procedure showed variations in the molecular mass of the polymer in the test samples; the molecular mass scatter amounted to 10 kDa. The dissolution profile of the test samples in an aqueous buffer solution (pH 5.59) was described by a linear function during the first hour. The slope characterising the dissolution rate varied from 10° to 36°.Conclusions. The variation in the molecular mass of hypromellose phthalate significantly affects the dissolution rate of the test samples. The function of the dissolution rate against the molecular mass of hypromellose phthalate is non-linear. The article provides a compelling reason for further research to derive a correlation equation for the dissolution rate of hypromellose phthalate as a function of two variables (molecular mass and proportion of phthalate groups in the polymer).

Short-chain polyphosphates: Extraction effects on migration and size estimation of Saccharomyces cerevisiae extracts with polyacrylamide gel electrophoresis.

Polyacrylamide gel electrophoresis is commonly used to characterize the chain length of polyphosphates (polyP), more generally called condensed phosphates. After separation, nonradioactive, optical polyP staining is limited to chain lengths greater than 15 monomers with toluidine blue or 4',6-diamidino-2-phenylindole. PolyP chain lengths longer than 62 monomers were correlated to the shortest DNA ladders. In this study, synthetic linear polyPs (Sigma-Aldrich "Type 45", estimated mean length of 45 monomers), trimetaphosphate (trimetaP: 3 ring), tripolyphosphate (tripolyP), pyrophosphate (PPi ), and inorganic orthophosphate (o-Pi ) were visualized after separation by an in situ hydrolytic degradation process to o-Pi that was subsequently stained with methyl green. Statistically insignificant migration reduction of synthetic short-chain polyP after perchloric acid or phenol-chloroform extraction was confirmed with the Friedman test. 31 P diffusion-ordered NMR spectroscopy confirmed that extraction also reduced PPi diffusivity by <10%. Linear regression between the Rf peak migration value and the logarithm of synthetic polyP molecular weights enabled estimation of extracted polyP chain lengths from 2 to 45 monomers. Linear polyP extracts from Saccharomyces cerevisiae grown in aerobic conditions were generally shorter than extracts cultured in anaerobic conditions. Extractions from both aerobic and anaerobic S. cerevisiae included tripolyP and o-Pi , but no PPi .

Direct Extraction of Sodium Hydroxide by Calix[4]pyrrole-Based Ion-Pair Receptors.

Described in this work are calix[4]pyrrole-based ion-pair receptors, cis/trans-1 and cis/trans-2, designed for the extraction of sodium hydroxide. An X-ray diffraction analysis of a single crystal of the cis-1·NaOH isomer isolated from a mixture of cis/trans-1 revealed a unique dimeric supramolecular structure. An average dimer in toluene-d8 solution was inferred on the basis of diffusion-ordered spectroscopy (DOSY). Support for the proposed stoichiometry came from density functional theory (DFT) calculations. The structural stability of the dimeric cis-1·NaOH complex in toluene solution was further confirmed by ab initio molecular dynamics (AIMD) simulation with explicit representation of solvent. Under conditions of liquid-liquid extraction (LLE), purified receptors cis- and trans-2 were both found to remove NaOH from a pH 11.01 aqueous source phase into toluene with extraction efficiencies (E%) of 50-60% when used equimolar to NaOH. However, in all cases, precipitation was observed. Complexities associated with precipitation could be avoided by immobilization of the receptors onto a chemically inert poly(styrene) resin by means of solvent impregnation. The use of solvent-impregnated resins (SIRs) eliminated precipitation in solution while retaining the extraction efficiency toward NaOH. This allowed both the pH and salinity of the alkaline source phase to be lowered.

Diffusion-Ordered Spectroscopy for Rapid and Facile Determination of Consumer Plastic Molecular Weight.

Molecular weight (MW) is a key control of plastic polymer properties and their fate in the environment. However, the primary tool used to determine plastic MW, gel permeation chromatography (GPC), has major limitations, such as low precision and accuracy, requirements for dedicated instrumentation, production of high volumes of hazardous waste, and large sample sizes. In this study, we describe, validate, and apply a diffusion-ordered spectroscopy (DOSY) method for polymer MW determinations, with a focus on applications for consumer plastics. Several experimental conditions were systematically optimized and tested to validate the DOSY method, including the selection of pulse sequences, the effect of sample concentration, cross-validation with multiple sets of external standards, and long-term instrumental stability. Validation was performed for a wide range of polymers, solvents, and temperatures, highlighting its potential for broad applicability. A preliminary screening of polystyrene and polyethylene terephthalate consumer products revealed widely varying MWs (up to two-fold) for products made of the same polymer type. A preliminary experiment was also conducted to track the decrease in polystyrene MW via photochemical chain scission reactions, finding a 20% reduction in MW after less than 1 week of irradiation. Collectively, our results demonstrate the potential for DOSY to provide high-throughput, accurate, and precise measures of polymer MW, as well as the evolution of polymer MW during environmental weathering processes, such as photochemical degradation. We conclude with a discussion of (i) the many advantages of DOSY compared to GPC, (ii) future developments to enhance the depth of information obtained from DOSY, and (iii) approaches to broaden the accessibility of this promising analytical method to the research community.

Ligands on Nanocrystal Surfaces, the 1H Nuclear Magnetic Resonance Fingerprint.

ConspectusSurfaces are an integral part of colloidal nanocrystals (NCs). Hence, understanding the binding and packing to NC surfaces of organic ligands, which are often used to stabilize NC colloids, is an essential aspect of the formation of NCs with desired chemical or physical properties. Since NCs lack a unique structure, not a single analytical technique can provide a complete description of the chemistry of NC surfaces. Even so, solution 1H nuclear magnetic resonance spectroscopy stands out as a unique method to study the organic ligand shell for its capability to distinguish between surface bound species and surface inactive residues from NC synthesis and purification.In this account, we first set the stage by highlighting the fingerprints of ligands bound to NCs in solution 1H NMR, which are broadened and shifted resonances, slow diffusion, and pronounced transfer of spin polarization between nearby protons. These characteristics enable bound ligands to be identified and quantified by 1D 1H NMR spectroscopy, diffusion-ordered spectroscopy (DOSY), and nuclear Overhauser effect spectroscopy (NOESY). Even so, we argue in a second part that much more insight in surface chemistry can be obtained from the in situ monitoring of ligand exchange processes. The chemical analysis of released compounds and the thermodynamic study of exchange equilibria provide a surprisingly detailed picture of the chemistry of the NC-ligand bond, the heterogeneity of binding sites, and the bunching of ligands on the NC surface. Multiple case studies are discussed to illustrate these different aspects of NC surface chemistry, where work on CdSe NCs in particular indicates that binding sites at facet edges are most vulnerable for ligand loss. While such weak binding sites are a liability for optoelectronic applications, they could offer an opportunity for catalysis. Moreover, the general character of the methodology introduced calls for realizing a broad, quantitative survey of NC-ligand interactions, well beyond the extensively studied case of CdSe NCs.In a third part, we address in more detail the line broadening that characterizes ligands bound to NCs, which results from a combination of reduced mobility and a diversity of chemical environments. Hence, chemical shift and line shape, or rates of transversal relaxation and interligand cross-relaxation, can all convey information on the ligand environment, especially when solvents are used that are chemically distinct from the ligand chain, such as aromatic versus aliphatic. Two examples that illustrate this point are the relation between line width and ligand solvation, where better solvated ligands yield more narrow resonances, and the possibility to identify different parts of the inhomogeneously broadened resonance with ligands bound on different locations at the NC surface. Interestingly, such results question the limits of NC size and ligand packing density at which the current bound-ligand paradigm, modest inhomogeneous broadening, will break down. Building on this question, we summarize in a final part the current status of NC ligand analysis by solution 1H NMR and outline directions for further research.

Combination of Drug Delivery Properties of PAMAM Dendrimers and Cytotoxicity of Platinum(IV) Complexes-A More Selective Anticancer Treatment?

Based on their drug delivery properties and activity against tumors, we combined PAMAM dendrimers with various platinum(IV) complexes in order to provide an improved approach of anticancer treatment. Platinum(IV) complexes were linked to terminal NH2 moieties of PAMAM dendrimers of generation 2 (G2) and 4 (G4) via amide bonds. Conjugates were characterized by 1H and 195Pt NMR spectroscopy, ICP-MS and in representative cases by pseudo-2D diffusion-ordered NMR spectroscopy. Additionally, the reduction behavior of conjugates in comparison to corresponding platinum(IV) complexes was investigated, showing a faster reduction of conjugates. Cytotoxicity was evaluated via the MTT assay in human cell lines (A549, CH1/PA-1, SW480), revealing IC50 values in the low micromolar to high picomolar range. The synergistic combination of PAMAM dendrimers and platinum(IV) complexes resulted in up to 200 times increased cytotoxic activity of conjugates in consideration of the loaded platinum(IV) units compared to their platinum(IV) counterparts. The lowest IC50 value of 780 ± 260 pM in the CH1/PA-1 cancer cell line was detected for an oxaliplatin-based G4 PAMAM dendrimer conjugate. Finally, in vivo experiments of a cisplatin-based G4 PAMAM dendrimer conjugate were performed based on the best toxicological profile. A maximum tumor growth inhibition effect of 65.6% compared to 47.6% for cisplatin was observed as well as a trend of prolonged animal survival.

Non-stoichiometric effect in the superacid-catalyzed polyhydroxyalkylation of biphenyl and 1-propyl isatin

An experimental study on the superacid-catalyzed polyhydroxyalkylation of biphenyl (A2 monomer) and 1-propyl isatin (B2 monomer) at non-stoichiometric conditions is presented. The produced high-performance polymers were characterized by gel permeation chromatography matrix-assisted laser-desorption/ionization-time-of-flight (MALDI-TOF), nuclear magnetic resonance and diffusion-ordered spectroscopy (DOSY). High molecular weights (Mw &gt; 150,000 Da) and ultra-high molecular weights (Mw ∼ 900,000 Da) are obtained when B2 is used in excess, which agrees with the behavior observed at non-stoichiometric conditions for other superacid catalyzed polyhydroxyalkylations, contrary to the case when A2 is used in excess, where a reduction in molecular weight is obtained, as reported in a previous study from our group. A, B, and M types of linear polymer molecules, as well as C-type cycles, were observed from the MALDI-TOF data.

Soft Side of Aliphatic Polycarbonates: with PCHC-b-PDMS Copolymers toward Ductile Materials

Aliphatic polycarbonates based on CO2 and epoxides are a promising group of polymers due to the utilization of CO2 as a monomer combined with a versatile epoxide feedstock. To increase the attractiveness of these polymers as a material, the poor mechanical properties have to be improved. Herein, we present the synthesis of block copolymers from poly(cyclohexene carbonate) and poly(dimethyl siloxane) (PDMS), where diffusion-ordered NMR spectroscopy measurements indicate a successful synthesis of block structures. The resulting material shows an elongation at break of up to 24% in tensile testing with an incorporation ratio of only 27% PDMS in the copolymer. At the same time, a high tensile strength (27.9 MPa) and modulus of elasticity (1726 MPa) are observed.

A Precise qNMR Method for the Rapid Quantification of Lot-to-Lot Variations in Multiple Quality Attributes of Pentosan Polysulfate Sodium.

Pentosan polysulfate sodium (PPS) is an orphan drug with anticoagulant activity. PPS is prepared from the chemical processing of xylan extracted from beechwood tree to yield a mixture of 4-6kDa polysaccharides. The chain is mainly composed of sulfated xylose (Xyl) with branched 4-O-methyl-glucuronate (MGA). During generic drug development, the quality attributes (QAs) including monosaccharide composition, modification, and length need to be comparable to those found in the reference list drug (RLD). However, the range of QA variation of the RLD PPS has not been well characterized. Here, multiple PPS RLD lots were studied using quantitative NMR (qNMR) and diffusion ordered spectroscopy (DOSY) to quantitate the components in the mixture and to probe both inter- and intra-lot precision variability. The DOSY precision assessed using coefficient of variation (CV) was 6%, comparable to PPS inter-lot CV of 5%. The QAs obtained from 1D qNMR were highly precise with a precision CV < 1%. The inter-lot MGA content was 4.8 ± 0.1%, indicating a very consistent botanical raw material source. Other process-related chemical modification including aldehyde at 0.51 ± 0.04%, acetylation at 3.3 ± 0.2% and pyridine at 2.08 ± 0.06%, varied more than MGA content. The study demonstrated that 1D qNMR is a quick and precise method to reveal ranges of variation in multiple attributes of RLD PPS which can be used to assess equivalency with generic formulations. Interestingly, the synthetic process appeared to introduce more variations to the PPS product than the botanical source of the material.

Polymer Molecular Weights via DOSY NMR

Diffusion-ordered spectroscopy (DOSY) 1H nuclear magnetic resonance (1H NMR) has become a powerful tool to characterize the molecular weights of polymers. Compared to common characterization techniques, such as size exclusion chromatography (SEC), DOSY is faster, uses less solvent, and does not require a purified polymer sample. Poly(methyl methacrylate) (PMMA), polystyrene (PS), and polybutadiene (PB) molecular weights were determined by the linear correlation between the logarithm of their diffusion coefficients (D) and the logarithm of their molecular weights based on SEC molecular weights. Here, we emphasize the importance of the preparation needed to generate the calibration curves, which includes choosing the correct pulse sequence, optimizing parameters, and sample preparation. The limitation of the PMMA calibration curve was investigated by increasing the dispersity of PMMA. Additionally, by accounting for viscosity in the Stokes-Einstein equation, a variety of solvents were used to produce a "universal" calibration curve for PMMA to determine molecular weight. Furthermore, we place a spotlight on the increasing importance of DOSY NMR being incorporated into the polymer chemist's toolbox.

Thermal oxidation of model molecules to reveal vegetable oil polymerization studied by NMR spectroscopy and self‐diffusion

AbstractOxidative polymerization of plant oils and lipids is poorly understood yet widely encountered. Oils and fats are renewable resources providing biofuels and polymers. Oil oxidation is accelerated at high temperatures, typically above 110°C, where triacylglycerides are converted into toxic compounds and viscous deleterious polymers. Polymerization of mono‐unsaturated oil (210°C, 3 h, open to air) was investigated by comparing four similar sized molecules with different functional groups: oleic acid, methyl oleate, trans‐7‐tetradecene, and stearic acid. Non‐volatile products identified by NMR spectroscopy are minor ketones for saturated fatty acid (stearic acid), epoxides for acyl chains without acid groups (methyl oleate, tetradecane) and copious oligomerization, through ester cross‐links, for acyl chains with acid, and olefinic groups (oleic acid). Long range CH coupling clearly shows ester (not ether) cross‐links, contradicting long‐held beliefs. Chain fragmentation also occurs for heated oleic acid as revealed by formation of a species with a methylene group bonded to oxygen of an ester, CH2OC(O). Large size (slow diffusion) of the first oligomer (trimer) formed from oleic acid, used to represent hydrolyzed vegetable oil, was evidenced by DOSY (diffusion‐ordered spectroscopy). Combined NMR results show oligomers found in heated oleic acid are fatty acid estolides. Model oil reactions demonstrate why olefin and carboxylic acid groups are required for polymerization.