Renny Mathew , Ivan V. Sergeyev , Fabien Aussenac , Lydia Gkoura , Melanie Rosay , Maria Baias
{"title":"从dnp增强的固态核磁共振中获得天然同位素丰度的药物的完整共振分配","authors":"Renny Mathew , Ivan V. Sergeyev , Fabien Aussenac , Lydia Gkoura , Melanie Rosay , Maria Baias","doi":"10.1016/j.ssnmr.2022.101794","DOIUrl":null,"url":null,"abstract":"<div><p>Solid-state dynamic nuclear polarization enhanced magic angle spinning (DNP-MAS) NMR measurements coupled with density functional theory (DFT) calculations enable the full resonance assignment of a complex pharmaceutical drug molecule without the need for isotopic enrichment. DNP dramatically enhances the NMR signals, thereby making possible previously intractable two-dimensional correlation NMR spectra at natural abundance. Using inputs from DFT calculations, herein we describe a significant improvement to the structure elucidation process for complex organic molecules. Further, we demonstrate that a series of two-dimensional correlation experiments, including <sup>15</sup>N–<sup>13</sup>C TEDOR, <sup>13</sup>C–<sup>13</sup>C INADEQUATE/SARCOSY, <sup>19</sup>F–<sup>13</sup>C HETCOR, and <sup>1</sup>H–<sup>13</sup>C HETCOR, can be obtained at natural isotopic abundance within reasonable experiment times, thus enabling a complete resonance assignment of sitagliptin, a pharmaceutical used for the treatment of type 2 diabetes.</p></div>","PeriodicalId":21937,"journal":{"name":"Solid state nuclear magnetic resonance","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0926204022000236/pdfft?md5=37edeb9b3fa6812c2fb544dd1320984c&pid=1-s2.0-S0926204022000236-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Complete resonance assignment of a pharmaceutical drug at natural isotopic abundance from DNP-Enhanced solid-state NMR\",\"authors\":\"Renny Mathew , Ivan V. Sergeyev , Fabien Aussenac , Lydia Gkoura , Melanie Rosay , Maria Baias\",\"doi\":\"10.1016/j.ssnmr.2022.101794\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Solid-state dynamic nuclear polarization enhanced magic angle spinning (DNP-MAS) NMR measurements coupled with density functional theory (DFT) calculations enable the full resonance assignment of a complex pharmaceutical drug molecule without the need for isotopic enrichment. DNP dramatically enhances the NMR signals, thereby making possible previously intractable two-dimensional correlation NMR spectra at natural abundance. Using inputs from DFT calculations, herein we describe a significant improvement to the structure elucidation process for complex organic molecules. Further, we demonstrate that a series of two-dimensional correlation experiments, including <sup>15</sup>N–<sup>13</sup>C TEDOR, <sup>13</sup>C–<sup>13</sup>C INADEQUATE/SARCOSY, <sup>19</sup>F–<sup>13</sup>C HETCOR, and <sup>1</sup>H–<sup>13</sup>C HETCOR, can be obtained at natural isotopic abundance within reasonable experiment times, thus enabling a complete resonance assignment of sitagliptin, a pharmaceutical used for the treatment of type 2 diabetes.</p></div>\",\"PeriodicalId\":21937,\"journal\":{\"name\":\"Solid state nuclear magnetic resonance\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2022-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0926204022000236/pdfft?md5=37edeb9b3fa6812c2fb544dd1320984c&pid=1-s2.0-S0926204022000236-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Solid state nuclear magnetic resonance\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0926204022000236\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Solid state nuclear magnetic resonance","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0926204022000236","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Complete resonance assignment of a pharmaceutical drug at natural isotopic abundance from DNP-Enhanced solid-state NMR
Solid-state dynamic nuclear polarization enhanced magic angle spinning (DNP-MAS) NMR measurements coupled with density functional theory (DFT) calculations enable the full resonance assignment of a complex pharmaceutical drug molecule without the need for isotopic enrichment. DNP dramatically enhances the NMR signals, thereby making possible previously intractable two-dimensional correlation NMR spectra at natural abundance. Using inputs from DFT calculations, herein we describe a significant improvement to the structure elucidation process for complex organic molecules. Further, we demonstrate that a series of two-dimensional correlation experiments, including 15N–13C TEDOR, 13C–13C INADEQUATE/SARCOSY, 19F–13C HETCOR, and 1H–13C HETCOR, can be obtained at natural isotopic abundance within reasonable experiment times, thus enabling a complete resonance assignment of sitagliptin, a pharmaceutical used for the treatment of type 2 diabetes.
期刊介绍:
The journal Solid State Nuclear Magnetic Resonance publishes original manuscripts of high scientific quality dealing with all experimental and theoretical aspects of solid state NMR. This includes advances in instrumentation, development of new experimental techniques and methodology, new theoretical insights, new data processing and simulation methods, and original applications of established or novel methods to scientific problems.