{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:20:09Z","timestamp":1788528009207,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,4,12]],"date-time":"2010-04-12T00:00:00Z","timestamp":1271030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chirality"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pyramidal inversion mechanisms of the 6\u2010methoxy and the 5\u2010methoxy tautomers of (<jats:italic>S<\/jats:italic>)\u2010omeprazole were studied, employing ab initio and DFT methods. The conformational space of the model molecule (<jats:italic>S<\/jats:italic>)\u20102\u2010[(3\u2010methyl\u20102\u2010pyridinyl)methyl]sulfinyl\u20101<jats:italic>H<\/jats:italic>\u2010benzimidazole was calculated, with respect to rotations around single bonds, at the B3LYP\/6\u2010311G(d,p) level. All of the resulting conformations were used as starting points for full optimizations of (<jats:italic>S<\/jats:italic>)\u2010omeprazole, at B3LYP\/6\u201031G(d), B3LYP\/6\u2010311G(d,p), B3LYP\/6\u2010311++G(d,p), B3LYP\/6\u2010311G(2df,2pd), MP2\/6\u201031G(d), and MP2\/6\u2010311G(d,p) levels. Four distinct pathways were found for enantiomerization via the pyramidal inversion mechanism for each of the tautomers of (<jats:italic>S<\/jats:italic>)\u2010omeprazole. Each transition state, in which the sulfur, the oxygen and the two carbon atoms connected directly to the sulfur are in one plane, connects two diastereomeric minima. The enantiomerization is completed by free rotation around the sulfur\u2013methylene bond, and around the methylene\u2013pyridine ring bond. The effective Gibbs' free energy barrier for racemization \u0394<jats:italic>G<\/jats:italic><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-stack-1.gif\" xlink:title=\"urn:x-wiley:08990042:media:CHIR20839:tex2gif-stack-1\"\/> of the two tautomers of (<jats:italic>S<\/jats:italic>)\u2010omeprazole are 39.8 kcal\/mol (5\u2010methoxy tautomer) and 40.0 kcal\/mol (6\u2010methoxy tautomer), indicating that the enantiomers of omeprazole are stable at room temperature (in the gas phase). The 5\u2010methoxy tautomer of (<jats:italic>S<\/jats:italic>)\u2010omeprazole was found to be slightly more stable than the 6\u2010methoxy tautomer, in the gas phase. The energy barrier (\u0394<jats:italic>G<\/jats:italic><jats:sup>\u2021<\/jats:sup>) for the(<jats:italic>S<\/jats:italic>,<jats:italic>M<\/jats:italic>)\n<jats:styled-content>$ \\rightleftharpoons $<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content>(<jats:italic>S<\/jats:italic>,<jats:italic>P<\/jats:italic>) diastereomerization of (<jats:italic>S<\/jats:italic>)\u2010omeprazole due to the rotation around the pyridine chiral axis was very low, 5.8 kcal\/mole at B3LYP\/6\u2010311G(d,p). Chirality 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/chir.20839","type":"journal-article","created":{"date-parts":[[2010,4,13]],"date-time":"2010-04-13T13:14:20Z","timestamp":1271164460000},"page":"798-807","source":"Crossref","is-referenced-by-count":7,"title":["Racemization of the gastrointestinal antisecretory chiral drug esomeprazole magnesium via the pyramidal inversion mechanism: A theoretical study"],"prefix":"10.1002","volume":"22","author":[{"given":"Hili","family":"Marom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Agranat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,4,12]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.2610100102"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1010"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/B0-08-045044-X\/00297-2"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0957-4166(97)00195-X"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd915"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/3527608001.ch6"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-200828050-00001"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2009.125"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01481.x"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/cen-v081n018.p045"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/3527608001.ch5"},{"key":"e_1_2_5_13_2","unstructured":"NEXIUMTM DRUGS@FDA NDA 21\u2010153\/21\u2010154. Available at:http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2001\/21153lbl.pdf."},{"key":"e_1_2_5_14_2","unstructured":"NEXIUMTM DRUGS@FDA NDA 21\u2010153\/S\u2010031 NDA 21\u2010957\/S\u2010003 NDA 22\u2010101\/S\u2010001. Available at:http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2009\/021153s031 021957s003 022101s001lbl.pdf. (Last accessed date 28.02.2010)."},{"key":"e_1_2_5_15_2","unstructured":"KAPIDEX DRUGS@FDA NDA 22\u2010287. Available at:http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2009\/022287s000_Lbl.pdf. (Last accessed date 28.02.2010)."},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)83781-0"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/chir.20214"},{"key":"e_1_2_5_18_2","first-page":"5","article-title":"The structure of omeprazole in the solid state: a 13C and 15N NMR\/CPMAS study","author":"Claramunt RM","year":"2006","journal-title":"ARKIVOC"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrc.1409"},{"key":"e_1_2_5_20_2","first-page":"1921","article-title":"Structure of 5\u2010methoxy\u20102\u2010[[(4\u2010methoxy\u20103,5\u2010dimethyl\u20102\u2010pyridinyl)methyl]sulfinyl]\u20101H\u2010benzimidazole (omeprazole)","volume":"45","author":"Ohishi H","year":"1989","journal-title":"Acta Crystallogr"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0957-4166(00)00114-2"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr60304a004"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470147153.ch2"},{"key":"e_1_2_5_24_2","first-page":"139","article-title":"Mechanisms of inversion at pyramidal sulfur atoms in three\u2010coordinate sulfur compounds","volume":"21","author":"Toyota S","year":"1999","journal-title":"Rev Heteroatom Chem"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01020a019"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01020a020"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01020a021"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00965a048"},{"key":"e_1_2_5_29_2","volume-title":"Exploring chemistry with electronic structure methods","author":"Foresman JB","year":"1995"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/chir.20417"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/qua.21597"},{"key":"e_1_2_5_32_2","volume-title":"Gaussian 98, Revision A.11.3","author":"Frisch MJ","year":"2002"},{"key":"e_1_2_5_33_2","volume-title":"Gaussian 03, Revision C.02","author":"Frisch MJ","year":"2004"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.464913"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.37.785"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2614(89)87234-3"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1139\/p80-159"},{"key":"e_1_2_5_38_2","first-page":"20","volume-title":"Stereochemistry of organic compounds","author":"Eliel EL","year":"1994"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470147238.ch1"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200901719"},{"key":"e_1_2_5_41_2","unstructured":"US Patent 6 262 085 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB. Alkoxy substituted benzimidazole compounds pharmaceutical preparations containing the same and methods of using the same 2001."},{"key":"e_1_2_5_42_2","unstructured":"US Patent 6 262 086 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB FontanaSA. Pharmaceutical unit dosage form.2001."},{"key":"e_1_2_5_43_2","unstructured":"US Patent 6 208 385 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB FontanaSA. Dry blend pharmaceutical formulations.2001."},{"key":"e_1_2_5_44_2","unstructured":"US Patent 6 312 712 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB MeyerGA. Method of improving bioavailability.2001."},{"key":"e_1_2_5_45_2","unstructured":"US Patent 6 312 723 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB MeyerGA FontanaSA. Pharmaceutical unit dosage form 2001."},{"key":"e_1_2_5_46_2","unstructured":"US Patent 6 316 020 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB MeyerGA. Pharmaceutical formulations 2001."},{"key":"e_1_2_5_47_2","unstructured":"US Patent 6 326 384 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB. Dry blend pharmaceutical unit dosage form 2001."},{"key":"e_1_2_5_48_2","unstructured":"US Patent 6 369 087 B1 WhittleRB SancilloFD StowellGW JenkinsDJ WhittallLB. Alkoxy substituted benzimidazole compounds pharmaceutical preparations containing the same and methods of using the same 2002."}],"container-title":["Chirality"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchir.20839","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chir.20839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:38:06Z","timestamp":1697438286000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/chir.20839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,12]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1002\/chir.20839"],"URL":"https:\/\/doi.org\/10.1002\/chir.20839","archive":["Portico"],"relation":{},"ISSN":["0899-0042","1520-636X"],"issn-type":[{"value":"0899-0042","type":"print"},{"value":"1520-636X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,12]]}}}