{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T18:05:56Z","timestamp":1758477956480,"version":"3.33.0"},"reference-count":23,"publisher":"International Union of Crystallography (IUCr)","issue":"9","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html#TDM"}],"funder":[{"name":"National Science Foundation through the Major Research Instrumentation Program","award":["CHE 1625543"],"award-info":[{"award-number":["CHE 1625543"]}]}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr C Struct Chem","Acta Crystallogr C","Acta Crystallogr C Cryst Struct Commun","Acta Cryst C","Acta Cryst C Struct Chem","Acta Cryst Sect C","Acta Cryst Sect C Struct Chem","Acta Crystallogr Sect C","Acta Crystallogr Sect C Struct Chem","Acta Crystallogr Sect C Cryst Struct Commun"],"accepted":{"date-parts":[[2019,7,30]]},"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:p>Phenytoin sodium, a salt of 5,5-diphenylimidazolidine-2,4-dione, or phenytoin, is commercially available in various dosage forms for its anti-epileptic properties to treat and prevent seizures. The title compound, poly[aquatris(\u03bc<jats:sub>3<\/jats:sub>-4,4-diphenyl-2,5-dioxoimidazolidin-1-ido)trimethanoltrisodium(I)], [Na<jats:sub>3<\/jats:sub>(C<jats:sub>15<\/jats:sub>H<jats:sub>11<\/jats:sub>N<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>)<jats:sub>3<\/jats:sub>(CH<jats:sub>4<\/jats:sub>O)<jats:sub>3<\/jats:sub>(H<jats:sub>2<\/jats:sub>O)<jats:sub>1.08<\/jats:sub>]<jats:sub>\n                     <jats:italic>n<\/jats:italic>\n                  <\/jats:sub>, a methanol solvate and hydrate of phenytoin sodium, forms a modulated crystal structure that consists of a supercell made up of three close-to-identical repeat units. Each of the basic fragments consists of one phenytoin anion, a sodium cation, and either a methanol, or a methanol and a water molecule coordinated to the sodium ion, yielding a formula unit of Na(C<jats:sub>15<\/jats:sub>H<jats:sub>11<\/jats:sub>N<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>)(CH<jats:sub>3<\/jats:sub>OH)<jats:sub>\n                     <jats:italic>x<\/jats:italic>\n                  <\/jats:sub>(H<jats:sub>2<\/jats:sub>O)<jats:sub>\n                     <jats:italic>y<\/jats:italic>\n                  <\/jats:sub> for each of the three segments (<jats:italic>x<\/jats:italic>, <jats:italic>y<\/jats:italic> = 0 or 1; <jats:italic>x<\/jats:italic>\u00a0+\u00a0<jats:italic>y<\/jats:italic> = 1 or 2). Modulation along the <jats:italic>b<\/jats:italic> axis is introduced due to the presence or absence of water or methanol molecules at sodium and by the alternating torsion angles of one of the two phenytoin phenyl rings. Individual segments within the asymmetric unit are linked by covalent Na\u2014O and Na\u2014N bonds, with each sodium ion coordinated to one anionic amide N atom and three keto O atoms. The Na\u2014N and one of the Na\u2014O bonds connect (C<jats:sub>15<\/jats:sub>H<jats:sub>11<\/jats:sub>N<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>)\u00b7Na units along the modulation direction, creating an infinite [(C<jats:sub>15<\/jats:sub>H<jats:sub>11<\/jats:sub>N<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>)\u00b7Na]_{\\infty} chain that is further stabilized by intramolecular N\u2014H...O hydrogen bonding parallel to [010]. The second Na\u2014O bond connects this chain with a symmetry-equivalent copy of itself created by a screw-axis operation, yielding double strands of [(C<jats:sub>15<\/jats:sub>H<jats:sub>11<\/jats:sub>N<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>)\u00b7Na]_{\\infty} chains. Two of these double strands, propagating in opposite directions, constitute the content of the unit cell. Neighboring double strands are connected with each other to form layers perpendicular to the <jats:italic>a<\/jats:italic> axis, tethered together <jats:italic>via<\/jats:italic> O\u2014H...O hydrogen bonds involving the water and methanol molecules. In addition to modulation, each of the repeat units also exhibits disorder of the modulated segments. Phenyl rings of each repeat unit are rotationally disordered, and sodium-coordinated methanol and water molecules are also positionally disordered and\/or partially occupied. The solvated structure reported here, while not matching the patterns reported for any of the known forms of phenytoin sodium, does provide a first insight into the complications and complexities involved in resolving the structure of anhydrous phenytoin sodium.<\/jats:p>","DOI":"10.1107\/s2053229619010696","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T15:05:51Z","timestamp":1565017551000},"page":"1213-1219","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":6,"title":["A threefold superstructure of the anti-epileptic drug phenytoin sodium as a mixed methanol solvate hydrate"],"prefix":"10.1107","volume":"75","author":[{"given":"Harsh S.","family":"Shah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaushalendra","family":"Chaturvedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Bates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2019,8,5]]},"reference":[{"unstructured":"Bosch, R. L., Johnson, P. R. & Stahl, R. J. (1998). International Patent No. WO1999048876A1.","key":"sk3736_bb1"},{"unstructured":"Bosch, R. L., Johnson, P. R. & Stahl, R. J. (2001). US Patent No. 6 245 917.","key":"sk3736_bb2"},{"unstructured":"Bruker (2016). APEX3 and SAINT. Bruker AXS Inc., Madison Wisconsin, USA.","key":"sk3736_bb3"},{"unstructured":"Budavari, S. (1996). In The Merck Index, 12th ed. Whitehouse Station, NJ: Merck & Co. Inc.","key":"sk3736_bb4"},{"key":"sk3736_bb5","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1107\/S0567740871005570","volume":"27","author":"Camerman","year":"1971","journal-title":"Acta Cryst. B"},{"key":"sk3736_bb6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF01195449","volume":"23","author":"Chattopadhyay","year":"1993","journal-title":"J. Crystallogr. Spectrosc. Res."},{"key":"sk3736_bb7","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1520\/JFS10282J","volume":"20","author":"Folen","year":"1975","journal-title":"J. Forensic Sci."},{"unstructured":"Gennaro, A. R. (1995). In Remington: The Science and Practice of Pharmacy. Easton, PA: Mack Publishing.","key":"sk3736_bb8"},{"key":"sk3736_bb9","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1097\/00007691-198612000-00021","volume":"8","author":"Glazko","year":"1986","journal-title":"Ther. Drug Monit."},{"unstructured":"Griesser, U. J. (2006). Polymorphism in the Pharmaceutical Industry, pp. 211-233: Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA.","key":"sk3736_bb10"},{"key":"sk3736_bb11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1107\/S2052520616003954","volume":"72","author":"Groom","year":"2016","journal-title":"Acta Cryst. B"},{"unstructured":"Hassel, T. (1981). Epilepsy and the Oral Manifestations of Phenytoin Therapy, Vol. 9, pp. 60-69. Basel: Karger Publishers.","key":"sk3736_bb12"},{"key":"sk3736_bb13","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1107\/S0021889811043202","volume":"44","author":"H\u00fcbschle","year":"2011","journal-title":"J. Appl. Cryst."},{"unstructured":"ICDD (2018). PDF-4+ 2018 and PDF4\/Organics (Database), edited by S. Kabekkodu. International Centre for Diffraction Data, Newtown Square, PA, USA.","key":"sk3736_bb14"},{"key":"sk3736_bb15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.molstruc.2018.05.030","volume":"1170","author":"Kalaiarasi","year":"2018","journal-title":"J. Mol. Struct."},{"key":"sk3736_bb16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S1600576714022985","volume":"48","author":"Krause","year":"2015","journal-title":"J. Appl. Cryst."},{"unstructured":"Krc, J. & Oviedo, J. (1993). Private Communication to the ICDD (ICDD 00-045-1557, ICDD 00-045-1558 and ICDD 00-045-1559). International Centre for Diffraction Data, Florida, USA.","key":"sk3736_bb17"},{"key":"sk3736_bb18","first-page":"105","volume":"42","author":"Krc","year":"1994","journal-title":"The Microscope"},{"key":"sk3736_bb19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijpharm.2015.01.031","volume":"480","author":"Moriyama","year":"2015","journal-title":"Int. J. Pharm."},{"unstructured":"Philip, J., Holcomb, I. J. & Fusari, S. A. (1984). Analytical Profiles of Drug Substances, Vol. 13, pp. 417-445. Amsterdam: Elsevier.","key":"sk3736_bb20"},{"key":"sk3736_bb22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Cryst. A"},{"key":"sk3736_bb23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Cryst. C"},{"unstructured":"USFDA. (2019). In Orange book: approved drug products with therapeutic equivalence evaluations, 39 ed. US Dpartment Of Health And Human Services.","key":"sk3736_bb24"}],"container-title":["Acta Crystallographica Section C Structural Chemistry"],"original-title":[],"link":[{"URL":"http:\/\/journals.iucr.org\/c\/issues\/2019\/09\/00\/sk3736\/sk3736.pdf","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.iucr.org\/c\/issues\/2019\/09\/00\/sk3736\/sk3736.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T10:48:37Z","timestamp":1736765317000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.iucr.org\/paper?S2053229619010696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,5]]},"references-count":23,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["S2053229619010696"],"URL":"https:\/\/doi.org\/10.1107\/s2053229619010696","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1107\/S2053229619010696\/sk3736sup1.cif","asserted-by":"subject"},{"id-type":"doi","id":"10.1107\/S2053229619010696\/sk3736Isup2.hkl","asserted-by":"subject"},{"id-type":"doi","id":"10.1107\/S2053229619010696\/sk3736sup3.pdf","asserted-by":"subject"}]},"ISSN":["2053-2296"],"issn-type":[{"type":"electronic","value":"2053-2296"}],"subject":[],"published":{"date-parts":[[2019,8,5]]},"assertion":[{"value":"Acta Crystallographica Section C: Structural Chemistry","order":0,"name":"journal","label":"Publication","explanation":{"URL":"http:\/\/journals.iucr.org\/c"},"group":{"name":"general","label":"General"}},{"value":"research papers","order":1,"name":"content_type","label":"Content type","explanation":{"URL":"https:\/\/journals.iucr.org\/c\/services\/notesforauthors.html"},"group":{"name":"general","label":"General"}},{"value":"Available","URL":"http:\/\/scripts.iucr.org\/cgi-bin\/citedin?sk3736","order":2,"name":"article_metrics","label":"Article metrics","group":{"name":"general","label":"General"}},{"value":"Yes","order":0,"name":"peer_reviewed","label":"Peer reviewed","group":{"name":"peer_review","label":"Peer review"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review process","group":{"name":"peer_review","label":"Peer review"}},{"value":"20 July 2019","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication history"}},{"value":"30 July 2019","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication history"}},{"value":"5 August 2019","order":2,"name":"published_online","label":"Published online","group":{"name":"publication_history","label":"Publication history"}},{"value":"This article has supporting information","name":"supplementary_materials","label":"Supplementary materials","explanation":{"URL":"http:\/\/scripts.iucr.org\/cgi-bin\/sendsup?sk3736"}},{"value":"\u00a9 2019 International Union of Crystallography","order":0,"name":"copyright","label":"Copyright","explanation":{"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},"group":{"name":"copyright_and_licensing","label":"Copyright and licencing"}}]}}