{"id":"https://openalex.org/W4388565748","doi":"https://doi.org/10.1021/acs.molpharmaceut.3c00764","title":"Solid-State NMR Spectroscopy to Probe State and Phase Transitions in Frozen Solutions","display_name":"Solid-State NMR Spectroscopy to Probe State and Phase Transitions in Frozen Solutions","publication_year":2023,"publication_date":"2023-11-10","ids":{"openalex":"https://openalex.org/W4388565748","doi":"https://doi.org/10.1021/acs.molpharmaceut.3c00764","pmid":"https://pubmed.ncbi.nlm.nih.gov/37947441"},"language":"en","primary_location":{"id":"doi:10.1021/acs.molpharmaceut.3c00764","doi":"https://doi.org/10.1021/acs.molpharmaceut.3c00764","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.molpharmaceut.3c00764","pdf_url":null,"source":{"id":"https://openalex.org/S204562082","display_name":"Molecular Pharmaceutics","issn_l":"1543-8384","issn":["1543-8384","1543-8392"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Pharmaceutics","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5101649851","display_name":"Yong Du","orcid":"https://orcid.org/0000-0002-1077-382X","observed_orcids":["https://orcid.org/0000-0002-1077-382X"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yong Du","raw_affiliation_strings":["Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States"],"raw_orcid":"https://orcid.org/0000-0002-1077-382X","affiliations":[{"raw_affiliation_string":"Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066932383","display_name":"Jinghan Li","orcid":"https://orcid.org/0000-0003-1863-5576","observed_orcids":["https://orcid.org/0000-0003-1863-5576"]},"institutions":[{"id":"https://openalex.org/I130238516","display_name":"University of Minnesota","ror":"https://ror.org/017zqws13","country_code":"US","type":"education","lineage":["https://openalex.org/I130238516"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jinghan Li","raw_affiliation_strings":["Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States"],"raw_orcid":"https://orcid.org/0000-0003-1863-5576","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States","institution_ids":["https://openalex.org/I130238516"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002578606","display_name":"Wei Xu","orcid":"https://orcid.org/0000-0003-3460-0330","observed_orcids":["https://orcid.org/0000-0003-3460-0330"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wei Xu","raw_affiliation_strings":["Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006758150","display_name":"Aaron S. Cote","orcid":"https://orcid.org/0009-0002-6486-2542","observed_orcids":["https://orcid.org/0009-0002-6486-2542"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Aaron Cote","raw_affiliation_strings":["Biologics Process Research and Development, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biologics Process Research and Development, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025129087","display_name":"Ashley Lay-Fortenbery","orcid":"https://orcid.org/0000-0003-0229-3719","observed_orcids":["https://orcid.org/0000-0003-0229-3719"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ashley Lay-Fortenbery","raw_affiliation_strings":["Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States","institution_ids":["https://openalex.org/I1285764155"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069911358","display_name":"Raj Suryanarayanan","orcid":"https://orcid.org/0000-0002-6322-0575","observed_orcids":["https://orcid.org/0000-0002-6322-0575"]},"institutions":[{"id":"https://openalex.org/I130238516","display_name":"University of Minnesota","ror":"https://ror.org/017zqws13","country_code":"US","type":"education","lineage":["https://openalex.org/I130238516"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Raj Suryanarayanan","raw_affiliation_strings":["Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States"],"raw_orcid":"https://orcid.org/0000-0002-6322-0575","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States","institution_ids":["https://openalex.org/I130238516"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5079691148","display_name":"Yongchao Su","orcid":"https://orcid.org/0000-0001-5063-3218","observed_orcids":["https://orcid.org/0000-0001-5063-3218"]},"institutions":[{"id":"https://openalex.org/I1285764155","display_name":"Merck & Co., Inc., Rahway, NJ, USA (United States)","ror":"https://ror.org/02891sr49","country_code":"US","type":"company","lineage":["https://openalex.org/I1285764155"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Yongchao Su","raw_affiliation_strings":["Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States","Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States"],"raw_orcid":"https://orcid.org/0000-0001-5063-3218","affiliations":[{"raw_affiliation_string":"Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States","institution_ids":["https://openalex.org/I1285764155"]},{"raw_affiliation_string":"Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States","institution_ids":["https://openalex.org/I1285764155"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5069911358","https://openalex.org/A5079691148"],"corresponding_institution_ids":["https://openalex.org/I1285764155","https://openalex.org/I130238516"],"apc_list":{"value":5000,"currency":"USD","value_usd":5000},"apc_paid":null,"fwci":1.4729,"has_fulltext":false,"cited_by_count":16,"citation_normalized_percentile":{"value":0.80462725,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":96,"max":99},"biblio":{"volume":"20","issue":"12","first_page":"6380","last_page":"6390"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11809","display_name":"Advanced NMR Techniques and Applications","score":0.9761000275611877,"subfield":{"id":"https://openalex.org/subfields/1607","display_name":"Spectroscopy"},"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/T11809","display_name":"Advanced NMR Techniques and Applications","score":0.9761000275611877,"subfield":{"id":"https://openalex.org/subfields/1607","display_name":"Spectroscopy"},"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/T11124","display_name":"Protein purification and stability","score":0.006300000008195639,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12603","display_name":"NMR spectroscopy and applications","score":0.0031999999191612005,"subfield":{"id":"https://openalex.org/subfields/3106","display_name":"Nuclear and High Energy Physics"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/solid-state-nmr","display_name":"solid-state NMR","score":0.8199999928474426},{"id":"https://openalex.org/keywords/freezing","display_name":"freezing","score":0.45500001311302185},{"id":"https://openalex.org/keywords/phase-transitions","display_name":"phase transitions","score":0.7929999828338623},{"id":"https://openalex.org/keywords/freeze-drying","display_name":"freeze-drying","score":0.5120000243186951},{"id":"https://openalex.org/keywords/trehalose","display_name":"trehalose","score":0.746999979019165},{"id":"https://openalex.org/keywords/histidine","display_name":"histidine","score":0.7789999842643738},{"id":"https://openalex.org/keywords/unfrozen-water-content","display_name":"unfrozen water content","score":0.7699999809265137},{"id":"https://openalex.org/keywords/solute-mobility","display_name":"solute mobility","score":0.5080000162124634},{"id":"https://openalex.org/keywords/monoclonal-antibody-formulations","display_name":"monoclonal antibody formulations","score":0.7879999876022339},{"id":"https://openalex.org/keywords/dupilumab","display_name":"dupilumab","score":0.9990000128746033},{"id":"https://openalex.org/keywords/biopharmaceuticals","display_name":"biopharmaceuticals","score":0.7450000047683716},{"id":"https://openalex.org/keywords/ph-measurement","display_name":"pH measurement","score":0.4580000042915344},{"id":"https://openalex.org/keywords/31p-nmr-spectroscopy","display_name":"31P NMR","score":0.6779999732971191},{"id":"https://openalex.org/keywords/13c-nmr-spectroscopy","display_name":"13C NMR","score":0.8880000114440918}],"concepts":[{"id":"https://openalex.org/C153202636","wikidata":"https://www.wikidata.org/wiki/Q7557802","display_name":"Solid-state nuclear magnetic resonance","level":2,"score":0.6804590225219727},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6737580895423889},{"id":"https://openalex.org/C66974803","wikidata":"https://www.wikidata.org/wiki/Q10359898","display_name":"Nuclear magnetic resonance spectroscopy","level":2,"score":0.5995165109634399},{"id":"https://openalex.org/C203036418","wikidata":"https://www.wikidata.org/wiki/Q284256","display_name":"Crystallization","level":2,"score":0.5344691872596741},{"id":"https://openalex.org/C32891209","wikidata":"https://www.wikidata.org/wiki/Q483666","display_name":"Spectroscopy","level":2,"score":0.5342995524406433},{"id":"https://openalex.org/C2778460671","wikidata":"https://www.wikidata.org/wiki/Q485277","display_name":"Histidine","level":3,"score":0.49093297123908997},{"id":"https://openalex.org/C21368211","wikidata":"https://www.wikidata.org/wiki/Q689863","display_name":"Synchrotron","level":2,"score":0.4790690839290619},{"id":"https://openalex.org/C113196181","wikidata":"https://www.wikidata.org/wiki/Q485223","display_name":"Analytical Chemistry (journal)","level":2,"score":0.39600884914398193},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.3827950954437256},{"id":"https://openalex.org/C46141821","wikidata":"https://www.wikidata.org/wiki/Q209402","display_name":"Nuclear magnetic resonance","level":1,"score":0.2360149323940277},{"id":"https://openalex.org/C43617362","wikidata":"https://www.wikidata.org/wiki/Q170050","display_name":"Chromatography","level":1,"score":0.22292375564575195},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.1325850486755371},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.11916255950927734},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.0},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","level":1,"score":0.0},{"id":"https://openalex.org/C185544564","wikidata":"https://www.wikidata.org/wiki/Q81197","display_name":"Nuclear physics","level":1,"score":0.0},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.0}],"mesh":[{"descriptor_ui":"D001688","descriptor_name":"Biological Products","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D005612","descriptor_name":"Freeze Drying","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005615","descriptor_name":"Freezing","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006639","descriptor_name":"Histidine","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009682","descriptor_name":"Magnetic Resonance Spectroscopy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010710","descriptor_name":"Phosphates","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012996","descriptor_name":"Solutions","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014961","descriptor_name":"X-Ray Diffraction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.molpharmaceut.3c00764","doi":"https://doi.org/10.1021/acs.molpharmaceut.3c00764","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.molpharmaceut.3c00764","pdf_url":null,"source":{"id":"https://openalex.org/S204562082","display_name":"Molecular Pharmaceutics","issn_l":"1543-8384","issn":["1543-8384","1543-8392"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Pharmaceutics","raw_type":"journal-article"},{"id":"pmid:37947441","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37947441","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":"Molecular pharmaceutics","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320332932","display_name":"Merck Sharp and Dohme","ror":"https://ror.org/004nn4n27"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":45,"referenced_works":["https://openalex.org/W1967889181","https://openalex.org/W1976239392","https://openalex.org/W1978255854","https://openalex.org/W1979806209","https://openalex.org/W2011502589","https://openalex.org/W2012851941","https://openalex.org/W2019379775","https://openalex.org/W2024010712","https://openalex.org/W2026351476","https://openalex.org/W2029712458","https://openalex.org/W2048199422","https://openalex.org/W2048421180","https://openalex.org/W2060229787","https://openalex.org/W2070399131","https://openalex.org/W2080233769","https://openalex.org/W2087376522","https://openalex.org/W2091113012","https://openalex.org/W2111590216","https://openalex.org/W2132954592","https://openalex.org/W2133544079","https://openalex.org/W2151662689","https://openalex.org/W2152133376","https://openalex.org/W2564989434","https://openalex.org/W2742166627","https://openalex.org/W2911844036","https://openalex.org/W2984505117","https://openalex.org/W2995755986","https://openalex.org/W3007635923","https://openalex.org/W3009814870","https://openalex.org/W3017518245","https://openalex.org/W3035708010","https://openalex.org/W3039620150","https://openalex.org/W3107418741","https://openalex.org/W3108373990","https://openalex.org/W3109975779","https://openalex.org/W3110973116","https://openalex.org/W3112181227","https://openalex.org/W3127661501","https://openalex.org/W3137404925","https://openalex.org/W4235601805","https://openalex.org/W4281480446","https://openalex.org/W4294671716","https://openalex.org/W4383373149","https://openalex.org/W4385514081","https://openalex.org/W4394958699"],"related_works":["https://openalex.org/W4394958699","https://openalex.org/W4404464729","https://openalex.org/W1504366750","https://openalex.org/W4318184885","https://openalex.org/W3112181227","https://openalex.org/W35777660","https://openalex.org/W4391650677","https://openalex.org/W1969105492","https://openalex.org/W4366960865","https://openalex.org/W2971104251"],"abstract_inverted_index":{"Freezing":[0],"is":[1,23],"commonly":[2],"encountered":[3],"during":[4],"the":[5,14,26,93,100,103,142,153,185],"processing":[6],"and":[7,16,47,65,72,77,90,131,147,189,196],"storage":[8],"of":[9,29,52,96,98,102,169,187],"biomacromolecule":[10],"products.":[11],"Therefore,":[12],"understanding":[13],"phase":[15],"state":[17,151],"transitions":[18],"in":[19,112,144,152],"pharmaceutical":[20],"frozen":[21],"solutions":[22,41],"crucial":[24],"for":[25],"rational":[27],"development":[28],"biopharmaceuticals.":[30],"Solid-state":[31],"nuclear":[32],"magnetic":[33],"resonance":[34],"spectroscopy":[35,176],"(ssNMR)":[36],"was":[37,67,106,115],"used":[38,136],"to":[39,140,162,183],"analyze":[40],"containing":[42],"sodium":[43],"phosphate":[44,54],"buffer,":[45],"histidine,":[46],"trehalose.":[48],"Upon":[49],"freezing,":[50],"crystallization":[51],"disodium":[53],"hydrogen":[55],"dodecahydrate":[56],"(Na":[57],"2":[58,62],"HPO":[59],"4":[60],"\u00b712H":[61],"O,":[63],"DPDH)":[64],"histidine":[66,85],"identified":[68],"using":[69],"31":[70],"P":[71],"13":[73,123],"C":[74],"ssNMR,":[75],"respectively,":[76],"confirmed":[78],"by":[79,117,127],"synchrotron":[80],"X-ray":[81],"diffractometry":[82],"(SXRD).":[83],"Using":[84],"as":[86,137,177],"a":[87,145,148,163,178],"molecular":[88],"probe":[89],"based":[91],"on":[92],"chemical":[94],"shifts":[95],"atoms":[97],"interest,":[99],"pH":[101],"freeze":[104,113],"concentrate":[105],"measured.":[107],"The":[108,157],"unfrozen":[109],"water":[110],"content":[111],"concentrates":[114],"quantified":[116],"1":[118],"H":[119],"single":[120],"pulse":[121],"experiments.":[122],"C-insensitive":[124],"nuclei":[125],"enhancement":[126],"polarization":[128],"transfer":[129],"(INEPT)":[130],"cross-polarization":[132],"(CP)":[133],"experiments":[134],"were":[135,160],"orthogonal":[138],"tools":[139],"characterize":[141],"solutes":[143],"\u201cmobile\u201d":[146],"more":[149],"\u201csolid-like\u201d":[150],"freeze-concentrated":[154],"solutions,":[155],"respectively.":[156],"above":[158],"analyses":[159],"applied":[161],"commercial":[164],"monoclonal":[165],"antibody":[166],"(mAb)":[167],"formulation":[168,197],"dupilumab.":[170],"This":[171],"work":[172],"further":[173],"establishes":[174],"ssNMR":[175],"highly":[179],"capable":[180],"biophysical":[181],"tool":[182],"investigate":[184],"attributes":[186],"biopharmaceuticals":[188],"thereby":[190],"provide":[191],"insights":[192],"into":[193],"process":[194],"optimization":[195],"development.":[198]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":8}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2023-11-11T00:00:00"}