{"id":"https://openalex.org/W7212224700","doi":"https://doi.org/10.1248/cpb.c26-00261","title":"Mechanistic Elucidation of the Acidic Hydrolysis of Triazolobenzodiazepines: Integration of Kinetic, Thermodynamic, and Quantum Chemical Analyses","display_name":"Mechanistic Elucidation of the Acidic Hydrolysis of Triazolobenzodiazepines: Integration of Kinetic, Thermodynamic, and Quantum Chemical Analyses","publication_year":2026,"publication_date":"2026-09-11","ids":{"openalex":"https://openalex.org/W7212224700","doi":"https://doi.org/10.1248/cpb.c26-00261","pmid":"https://pubmed.ncbi.nlm.nih.gov/42732943"},"language":"en","primary_location":{"id":"doi:10.1248/cpb.c26-00261","doi":"https://doi.org/10.1248/cpb.c26-00261","is_oa":true,"landing_page_url":"https://doi.org/10.1248/cpb.c26-00261","pdf_url":"https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00261/_pdf","source":{"id":"https://openalex.org/S3861430","display_name":"Chemical and Pharmaceutical Bulletin","issn_l":"0009-2363","issn":["0009-2363","1347-5223"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","jufo-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310313382","host_organization_name":"Pharmaceutical Society of Japan","host_organization_lineage":["https://openalex.org/P4310313382"],"host_organization_lineage_names":["Pharmaceutical Society of Japan"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical and Pharmaceutical Bulletin","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"diamond","oa_url":"https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00261/_pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5151407463","display_name":"Koichi Saito","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Koichi Saito","raw_affiliation_strings":["Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan","institution_ids":["https://openalex.org/I36296616"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Kentaro Tsutsumi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kentaro Tsutsumi","raw_affiliation_strings":["Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan","institution_ids":["https://openalex.org/I36296616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5151344566","display_name":"Misayo Iguchi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Misayo Iguchi","raw_affiliation_strings":["Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan","institution_ids":["https://openalex.org/I36296616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020002648","display_name":"Rie Ito","orcid":"https://orcid.org/0000-0001-9026-4939","observed_orcids":["https://orcid.org/0000-0001-9026-4939"]},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Rie Ito","raw_affiliation_strings":["Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan","institution_ids":["https://openalex.org/I36296616"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5090659492","display_name":"Hiroshi Akiyama","orcid":"https://orcid.org/0000-0002-7764-8601","observed_orcids":["https://orcid.org/0000-0002-7764-8601"]},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Hiroshi Akiyama","raw_affiliation_strings":["Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Analytical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2\u20134\u201341 Ebara, Shinagawa-ku, Tokyo 142\u20138501, Japan","institution_ids":["https://openalex.org/I36296616"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I36296616"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.5387407,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"74","issue":"9","first_page":"693","last_page":"698"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11460","display_name":"Analytical Methods in Pharmaceuticals","score":0.524399995803833,"subfield":{"id":"https://openalex.org/subfields/1602","display_name":"Analytical Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11460","display_name":"Analytical Methods in Pharmaceuticals","score":0.524399995803833,"subfield":{"id":"https://openalex.org/subfields/1602","display_name":"Analytical Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12191","display_name":"Physical Organic Chemistry and Reaction Kinetics","score":0.3174000084400177,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T13105","display_name":"Synthesis and pharmacology of benzodiazepine derivatives","score":0.13099999725818634,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/triazolobenzodiazepines","display_name":"triazolobenzodiazepines","score":0.9990000128746033},{"id":"https://openalex.org/keywords/alprazolam","display_name":"alprazolam","score":0.9279999732971191},{"id":"https://openalex.org/keywords/triazolam","display_name":"triazolam","score":1.0},{"id":"https://openalex.org/keywords/etizolam","display_name":"etizolam","score":1.0},{"id":"https://openalex.org/keywords/acid-hydrolysis","display_name":"acid hydrolysis","score":0.9470000267028809},{"id":"https://openalex.org/keywords/degradation-kinetics","display_name":"degradation kinetics","score":0.7300000190734863},{"id":"https://openalex.org/keywords/reaction-mechanism","display_name":"reaction mechanism","score":0.7250000238418579},{"id":"https://openalex.org/keywords/protonation","display_name":"protonation","score":0.7179999947547913},{"id":"https://openalex.org/keywords/water-nucleophilic-attack","display_name":"water nucleophilic attack","score":0.8460000157356262},{"id":"https://openalex.org/keywords/artificial-gastric-juice","display_name":"artificial gastric juice","score":0.7350000143051147},{"id":"https://openalex.org/keywords/drug-stability","display_name":"drug stability","score":0.5799999833106995}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7635999917984009},{"id":"https://openalex.org/C2991951333","wikidata":"https://www.wikidata.org/wiki/Q188403","display_name":"Quantum chemical","level":3,"score":0.6775000095367432},{"id":"https://openalex.org/C94412978","wikidata":"https://www.wikidata.org/wiki/Q103135","display_name":"Hydrolysis","level":2,"score":0.5514000058174133},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.3546000123023987},{"id":"https://openalex.org/C84114770","wikidata":"https://www.wikidata.org/wiki/Q46344","display_name":"Quantum","level":2,"score":0.3077999949455261},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.2985000014305115},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.2606000006198883},{"id":"https://openalex.org/C18762648","wikidata":"https://www.wikidata.org/wiki/Q42213","display_name":"Work (physics)","level":2,"score":0.25760000944137573},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.2574000060558319},{"id":"https://openalex.org/C65024703","wikidata":"https://www.wikidata.org/wiki/Q373406","display_name":"Reaction mechanism","level":3,"score":0.2556999921798706},{"id":"https://openalex.org/C177801218","wikidata":"https://www.wikidata.org/wiki/Q36534","display_name":"Chemical reaction","level":2,"score":0.2506999969482422}],"mesh":[{"descriptor_ui":"D001569","descriptor_name":"Benzodiazepines","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006868","descriptor_name":"Hydrolysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014230","descriptor_name":"Triazoles","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1248/cpb.c26-00261","doi":"https://doi.org/10.1248/cpb.c26-00261","is_oa":true,"landing_page_url":"https://doi.org/10.1248/cpb.c26-00261","pdf_url":"https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00261/_pdf","source":{"id":"https://openalex.org/S3861430","display_name":"Chemical and Pharmaceutical Bulletin","issn_l":"0009-2363","issn":["0009-2363","1347-5223"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","jufo-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310313382","host_organization_name":"Pharmaceutical Society of Japan","host_organization_lineage":["https://openalex.org/P4310313382"],"host_organization_lineage_names":["Pharmaceutical Society of Japan"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical and Pharmaceutical Bulletin","raw_type":"journal-article"},{"id":"pmid:42732943","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42732943","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical & pharmaceutical bulletin","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1248/cpb.c26-00261","doi":"https://doi.org/10.1248/cpb.c26-00261","is_oa":true,"landing_page_url":"https://doi.org/10.1248/cpb.c26-00261","pdf_url":"https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00261/_pdf","source":{"id":"https://openalex.org/S3861430","display_name":"Chemical and Pharmaceutical Bulletin","issn_l":"0009-2363","issn":["0009-2363","1347-5223"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","jufo-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310313382","host_organization_name":"Pharmaceutical Society of Japan","host_organization_lineage":["https://openalex.org/P4310313382"],"host_organization_lineage_names":["Pharmaceutical Society of Japan"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical and Pharmaceutical Bulletin","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7212224700.pdf","grobid_xml":"https://content.openalex.org/works/W7212224700.grobid-xml"},"referenced_works_count":12,"referenced_works":["https://openalex.org/W1517107496","https://openalex.org/W2002698305","https://openalex.org/W2022950330","https://openalex.org/W2029824321","https://openalex.org/W2032098290","https://openalex.org/W2033835706","https://openalex.org/W2048840186","https://openalex.org/W2077796804","https://openalex.org/W2768072658","https://openalex.org/W3134693074","https://openalex.org/W4362449090","https://openalex.org/W4401352844"],"related_works":["https://openalex.org/W2023451341","https://openalex.org/W2090090961","https://openalex.org/W2069916382","https://openalex.org/W4362449090","https://openalex.org/W2949311245","https://openalex.org/W1971282873","https://openalex.org/W2004949764","https://openalex.org/W2016338227","https://openalex.org/W2067183193","https://openalex.org/W3134693074"],"abstract_inverted_index":{"In":[0],"this":[1],"study,":[2],"the":[3,34,66,79,86,126,129,154,165],"degradation":[4,61,81,88],"behavior":[5],"and":[6,14,65,92,115,161],"reaction":[7,67],"mechanisms":[8],"of":[9,36,85,128,156,168],"triazolobenzodiazepines":[10],"(TBZDs)-alprazolam":[11],"(ALZ),":[12],"triazolam,":[13],"etizolam-in":[15],"artificial":[16,37],"gastric":[17,38],"juice":[18,39],"were":[19,23,107],"investigated.":[20],"Degradation":[21],"kinetics":[22],"evaluated":[24],"by":[25,90,135],"monitoring":[26],"time-dependent":[27],"changes":[28],"in":[29,171],"TBZD":[30],"standard":[31],"solutions":[32],"after":[33],"addition":[35],"at":[40],"various":[41],"temperatures":[42],"using":[43],"LC":[44],"with":[45],"photodiode":[46],"array":[47],"detection.":[48],"Arrhenius":[49],"analysis":[50,143],"provided":[51],"kinetic":[52],"parameters":[53],"for":[54],"each":[55],"compound.":[56],"All":[57],"TBZDs":[58,157],"underwent":[59],"rapid":[60],"under":[62,158],"acidic":[63,159],"conditions,":[64],"was":[68,76],"reversible,":[69],"yielding":[70],"a":[71],"single":[72],"major":[73],"product":[74,89],"that":[75,123,140],"characterized":[77],"as":[78,98],"final":[80],"product.":[82],"Structural":[83],"elucidation":[84],"ALZ":[87],"spectroscopic":[91],"mass":[93],"spectrometric":[94],"analyses":[95,121],"identified":[96],"it":[97],"(2-[3-(aminomethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-5-chlorophenyl)(phenyl)methanone.":[99],"To":[100],"gain":[101],"mechanistic":[102,151],"insight,":[103],"quantum":[104,146],"chemical":[105,147,169],"calculations":[106,148],"performed,":[108],"including":[109],"geometry":[110],"optimization,":[111],"electrostatic":[112],"potential":[113],"analysis,":[114],"frontier":[116],"molecular":[117],"orbital":[118],"analysis.":[119],"These":[120,137],"indicated":[122],"protonation":[124],"enhances":[125],"electrophilicity":[127],"azomethine":[130],"carbon,":[131],"facilitating":[132],"nucleophilic":[133],"attack":[134],"water.":[136],"findings":[138],"demonstrate":[139],"electronic":[141],"structure":[142],"based":[144],"on":[145],"provides":[149],"valuable":[150],"insight":[152],"into":[153],"hydrolysis":[155],"conditions":[160],"may":[162],"contribute":[163],"to":[164],"rational":[166],"assessment":[167],"stability":[170],"future":[172],"drug":[173],"development.":[174]},"counts_by_year":[],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2026-09-12T00:00:00"}
