{"title":"Dynamics of eugenol included in β-cyclodextrin by nuclear magnetic resonance and molecular simulations","authors":"Alejandro Hernández-Tanguma, Armando Ariza-Castolo","doi":"10.1002/mrc.5439","DOIUrl":"10.1002/mrc.5439","url":null,"abstract":"<p>Eugenol–β-cyclodextrin complex has been widely used because of the enhanced stability and conservation of the properties of eugenol. Applications in food and health sciences have been shown previously, which makes this complex an excellent model to understand and develop methodologies for the analysis and prediction of physical properties. In this work, the dynamics of eugenol incorporated into β-cyclodextrin are presented, using NMR relaxation rates, and the predictive capabilities of molecular dynamics simulations are discussed. Results show a hindered rotation of eugenol around the principal inertial axes when located inside β-cyclodextrin. Moreover, a translational movement of the whole complex is demonstrated.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 7","pages":"505-511"},"PeriodicalIF":2.0,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrc.5439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multinuclear 1H/13C/15N chemical shift assignment of therapeutic octreotide acetate performed at natural abundance","authors":"Alexander J. Menke, Fu Chen, Kang Chen","doi":"10.1002/mrc.5436","DOIUrl":"10.1002/mrc.5436","url":null,"abstract":"<p>Octreotide acetate, the active pharmaceutical ingredient in the long-acting release (LAR) drug product Sandostatin®, is a cyclic octapeptide that mimics the naturally occurring somatostatin peptide hormone. Modern NMR can be a robust analytical method to identify and quantify octreotide molecules. Previous <sup>1</sup>H chemical shift assignments were mostly performed in organic solvents, and no assignments for heteronuclear <sup>13</sup>C, <sup>15</sup>N, and aromatic <sup>1</sup>H nuclei are available. Here, using state-of-the-art 1D and 2D homo- and heteronuclear NMR experiments, octreotide was fully assigned, including water exchangeable amide protons, in aqueous buffer except for <sup>13</sup>CO and <sup>15</sup>NH of F1, <sup>15</sup>NH of C2, and <sup>15</sup>N<i>ζ</i>H<i>ζ</i> of K5 that were not observed because of water exchange or conformational exchange. The solution NMR spectra were then directly compared with 1D <sup>1</sup>H/<sup>13</sup>C/<sup>15</sup>N solid-state NMR (SSNMR) spectra showing the potential applicability of <sup>13</sup>C/<sup>15</sup>N SSNMR for octreotide drug product characterization.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 7","pages":"486-496"},"PeriodicalIF":2.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Measuring and modeling anisotropy in the NMR of solids","authors":"James K. Harper, Joshua D. Hartman","doi":"10.1002/mrc.5435","DOIUrl":"10.1002/mrc.5435","url":null,"abstract":"","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 3","pages":"124"},"PeriodicalIF":2.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ewa K. Nawrocka, Michał Jadwiszczak, Piotr J. Leszczyński, Krzysztof Kazimierczuk
{"title":"Supporting the assignment of NMR spectra with variable-temperature experiments","authors":"Ewa K. Nawrocka, Michał Jadwiszczak, Piotr J. Leszczyński, Krzysztof Kazimierczuk","doi":"10.1002/mrc.5433","DOIUrl":"10.1002/mrc.5433","url":null,"abstract":"<p>Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful tools in analytical chemistry. An important step in the analysis of NMR data is the assignment of resonance frequencies to the corresponding atoms in the molecule being investigated. The traditional approach considers the spectrum's characteristic parameters: chemical shift values, internuclear couplings, and peak intensities. In this paper, we show how to support the process of assigning a series of spectra of similar organic compounds by using temperature coefficients, that is, the rates of change in chemical shift values associated with given changes in temperature.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 7","pages":"479-485"},"PeriodicalIF":2.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrc.5433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacob Pellizzari, Ronald Soong, Katelyn Downey, Rajshree Ghosh Biswas, Flavio C. Kock, Katrina Steiner, Benjamin Goerling, Agnes Haber, Venita Decker, Falko Busse, Myrna Simpson, Andre Simpson
{"title":"Slice through the water—Exploring the fundamental challenge of water suppression for benchtop NMR systems","authors":"Jacob Pellizzari, Ronald Soong, Katelyn Downey, Rajshree Ghosh Biswas, Flavio C. Kock, Katrina Steiner, Benjamin Goerling, Agnes Haber, Venita Decker, Falko Busse, Myrna Simpson, Andre Simpson","doi":"10.1002/mrc.5431","DOIUrl":"10.1002/mrc.5431","url":null,"abstract":"<p>Benchtop NMR provides improved accessibility in terms of cost, space, and technical expertise. In turn, this encourages new users into the field of NMR spectroscopy. Unfortunately, many interesting samples in education and research, from beer to whole blood, contain significant amounts of water that require suppression in <sup>1</sup>H NMR in order to recover sample information. However, due to the significant reduction in chemical shift dispersion in benchtop NMR systems, the sample signals are much closer to the water resonance compared to those in a corresponding high-field NMR spectrum. Therefore, simply translating solvent suppression experiments intended for high-field NMR instruments to benchtop NMR systems without careful consideration can be problematic. In this study, the effectiveness of several popular water suppression schemes was evaluated for benchtop NMR applications. Emphasis is placed on pulse sequences with no, or few, adjustable parameters making them easy to implement. These fall into two main categories: (1) those based on Pre-SAT including Pre-SAT, PURGE, NOESY-PR, and g-NOESY-PR and (2) those based on binomial inversion including JRS and W5-WATERGATE. Among these schemes, solvent suppression sequences based on Pre-SAT offer a general approach for easy solvent suppression for samples with higher analyte concentrations (sucrose standard and Redbull™). However, for human urine, binomial-like sequences were required. In summary, it is demonstrated that highly efficient water suppression approaches can be implemented on benchtop NMR systems in a simple manner, despite the limited spectral dispersion, further illustrating the potential for widespread implementation of these approaches in education and research.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 6","pages":"463-473"},"PeriodicalIF":2.0,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrc.5431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junhe Ma, Qingmei Ye, Rebecca A. Green, John Gurak, Sloan Ayers, Yande Huang, Scott A. Miller
{"title":"Overcoming NMR line broadening of nitrogen containing compounds: A simple solution","authors":"Junhe Ma, Qingmei Ye, Rebecca A. Green, John Gurak, Sloan Ayers, Yande Huang, Scott A. Miller","doi":"10.1002/mrc.5432","DOIUrl":"10.1002/mrc.5432","url":null,"abstract":"<p>This study presents a straightforward solution to the challenge of elucidating the structures of nitrogen containing compounds undergoing isomerization. When spectral line broadening occurs related to isomerization, be it prototropic tautomerism or bond rotations, this poses a significant obstacle to structural elucidation. By adding acids, we demonstrate a simple approach to overcome this issue and effectively sharpen NMR signals for acid stable prototropic tautomers as well as the conformational isomers containing a morpholine or piperazine ring.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 3","pages":"198-207"},"PeriodicalIF":2.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Rossado Oliveira, Eric Tavares da Costa, Leonardo Araujo Schenberg, Lucas Colucci Ducati, Claudimir Lucio do Lago
{"title":"13C NMR as an analytical tool for the detection of carbonic acid and pKa determination","authors":"Daniel Rossado Oliveira, Eric Tavares da Costa, Leonardo Araujo Schenberg, Lucas Colucci Ducati, Claudimir Lucio do Lago","doi":"10.1002/mrc.5430","DOIUrl":"10.1002/mrc.5430","url":null,"abstract":"<p>NMR spectroscopy has become a standard technique in studies both on carbon capture and storage. <sup>13</sup>C NMR allows the detection of two peaks for carbonated aqueous samples: one for CO<sub>2(aq)</sub> and another one for the species H<sub>2</sub>CO<sub>3</sub>, HCO<sub>3</sub><sup>−</sup>, and CO<sub>3</sub><sup>2−</sup>—herein collectively named H<sub>x</sub>CO<sub>3</sub><sup>x-2</sup>. The chemical shift of this second peak depends on the molar fraction of the three species in equilibrium and has been used to assess the equilibrium between HCO<sub>3</sub><sup>−</sup> and CO<sub>3</sub><sup>2−</sup>. The detection of H<sub>2</sub>CO<sub>3</sub> at low pH solutions is hindered, because of the concurrent liberation of CO<sub>2</sub> when the medium is acidified. Herein, a valved NMR tube facilitates the detection of the H<sub>x</sub>CO<sub>3</sub><sup>x-2</sup> peak across a wide pH range, even at pH 1.8 where the dominant species is H<sub>2</sub>CO<sub>3</sub>. The method employed the formation of frozen layers of NaH<sup>13</sup>CO<sub>3</sub> and acid solutions within the tube, which are mixed as the tube reaches room temperature. At this point, the tube is already securely sealed, preventing any loss of CO<sub>2</sub> to the atmosphere. A spectrophotometry approach allowed the measurement of the actual pH inside the pressurized NMR tube. The chemical shift for H<sub>2</sub>CO<sub>3</sub> was determined as 160.33 ± 0.03 ppm, which is in good agreement with value obtained by DFT calculations combined with Car–Parrinello molecular dynamics. The H<sub>2</sub>CO<sub>3</sub> p<i>K</i><sub><i>a</i></sub> value determined by the present method was 3.41 ± 0.03, for 15% D<sub>2</sub>O aqueous medium and 0.8 mol/L ionic strength. The proposed method can be extended to studies about analogs such as alkyl carbonic and carbamic acids.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 2","pages":"114-120"},"PeriodicalIF":2.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The combination of inorganic phosphate and pyrophosphate 31P-NMR for the electrodeless pH determination in the 5–12 range","authors":"Paola Carta, Mariano Andrea Scorciapino","doi":"10.1002/mrc.5429","DOIUrl":"10.1002/mrc.5429","url":null,"abstract":"<p>Potentiometry is the primary pH measurement method, but alternatives are sought beyond glass electrodes operative limitations. In nuclear magnetic resonance (NMR) experiments, electrodeless pH sensing is important to track changes along titrations, during chemical reactions or inside compartmentalized environments inaccessible to electrodes, for instance. Although several interesting NMR pH indicators have been already presented, the potential of inorganic phosphate is overlooked, despite its common presence in NMR samples as the buffer main component. Its use for electrodeless pH determination can be expanded by exploiting all its three proton dissociations. This study was aimed at verifying the use of inorganic phosphate <sup>31</sup>P chemical shift to sense pH variations, and at exploring the complementary use of pyrophosphate ions to cover a wide pH range. A simple set of equations is presented to utilize both phosphate and pyrophosphate <sup>31</sup>P chemical shift in combination for accurate pH determination without a glass electrode over the 5–12 pH range, and without affecting the spectrum of other nuclei. The present study demonstrated an average deviation of 0.09 (maximum <0.2) pH unit from glass electrode measurements. The trimethylphosphate can be used as a suitable chemical shift reference for both <sup>31</sup>P and <sup>1</sup>H (also <sup>13</sup>C), with its hydrolysis being significant only at pH > 12. The method was also demonstrated by determining the pKa of three distinct molecules in a mixture and by comparing the results to those obtained when the glass electrode was used to measure the pH. The approach shown here can be easily tuned to different experimental conditions.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 2","pages":"101-113"},"PeriodicalIF":2.0,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evan R. McCarney, Kenneth A. Kristoffersen, Kathryn E. Anderssen
{"title":"Quantitative at-line monitoring of enzymatic hydrolysis using benchtop diffusion nuclear magnetic resonance spectroscopy","authors":"Evan R. McCarney, Kenneth A. Kristoffersen, Kathryn E. Anderssen","doi":"10.1002/mrc.5427","DOIUrl":"10.1002/mrc.5427","url":null,"abstract":"<p>Benchtop diffusion nuclear magnetic resonance (NMR) spectroscopy was used to perform quantitative monitoring of enzymatic hydrolysis. The study aimed to test the feasibility of the technology to characterize enzymatic hydrolysis processes in real time. Diffusion ordered spectroscopy (DOSY) was used to measure the signal intensity and apparent self-diffusion constant of solubilized protein in hydrolysate. The NMR technique was tested on an enzymatic hydrolysis reaction of red cod, a lean white fish, by the endopeptidase alcalase at 50°C. Hydrolysate samples were manually transferred from the reaction vessel to the NMR equipment. Measurement time was approximately 3 min per time point. The signal intensity from the DOSY experiment was used to measure protein concentration and the apparent self-diffusion constant was converted into an average molecular weight and an estimated degree of hydrolysis. These values were plotted as a function of time and both the rate of solubilization and the rate of protein breakdown could be calculated. In addition to being rapid and noninvasive, DOSY using benchtop NMR spectroscopy has an advantage compared with other enzymatic hydrolysis characterization methods as it gives a direct measure of average protein size; many functional properties of proteins are strongly influenced by protein size. Therefore, a method to give protein concentration and average size in real time will allow operators to more tightly control production from enzymatic hydrolysis. Although only one type of material was tested, it is anticipated that the method should be applicable to a broad variety of enzymatic hydrolysis feedstocks.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 6","pages":"452-462"},"PeriodicalIF":2.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrc.5427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NMR characterization of uniformly 13C- and/or 15N-labeled, unsulfated chondroitins with high molecular weights","authors":"Megumi Ichikawa, Yuya Otsuka, Toshikazu Minamisawa, Noriyoshi Manabe, Yoshiki Yamaguchi","doi":"10.1002/mrc.5426","DOIUrl":"10.1002/mrc.5426","url":null,"abstract":"<p>Solution nuclear magnetic resonance (NMR) analysis of polysaccharides can provide valuable information not only on their primary structures but also on their conformation, dynamics, and interactions under physiological conditions. One of the main problems is that non-anomeric <sup>1</sup>H signals typically overlap, and this often hinders detailed NMR analysis. Isotope enrichment, such as with <sup>13</sup>C and <sup>15</sup>N, will add a new dimension to the NMR spectra of polysaccharides, and spectral analysis can be performed with enhanced sensitivity using isolated peaks. For this purpose, here we have prepared uniformly <sup>13</sup>C- and/or <sup>15</sup>N-labeled chondroitin polysaccharides –4)-β-D-glucuronopyranosyl-(1–3)-2-acetamido-2-deoxy-β-D-galactopyranosyl-(1– with molecular weights in the range from 310 to 460 k by bacterial fermentation. The enrichment ratios for <sup>13</sup>C and <sup>15</sup>N were 98.9 and 99.8%, respectively, based on the mass spectrometric analysis of the constituent chondroitin disaccharides. <sup>1</sup>H and <sup>13</sup>C NMR signals were assigned mainly based on HSQC and <sup>13</sup>C-detection experiments including INADEQUATE, HETCOR, and HETCOR-TOCSY. The carbonyl carbon signal of the <i>N</i>-acetyl-β-D-galactosamine residue was unambiguously distinguished from the C6 carbon of the β-D-glucuronic acid residue by the observation of <sup>13</sup>C peak splitting due to <sup>1</sup><i>J</i><sub>CN</sub> coupling in <sup>13</sup>C- and <sup>15</sup>N-labeled chondroitin. The <i>T</i><sub>2</sub>* and <i>T</i><sub>1</sub> were measured and indicate that both rigid and mobile sites are present in the long sequence of chondroitin. The conformation, dynamics, and interactions of chondroitin and its derivatives will be further analyzed based on the results obtained in this study.</p>","PeriodicalId":18142,"journal":{"name":"Magnetic Resonance in Chemistry","volume":"62 6","pages":"439-451"},"PeriodicalIF":2.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}