{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:11:20Z","timestamp":1780513880507,"version":"3.54.1"},"reference-count":25,"publisher":"International Union of Crystallography (IUCr)","issue":"12","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html#TDM"}],"funder":[{"name":"The Drug Innovation Major Project of China","award":["2018ZX09711001-007-002"],"award-info":[{"award-number":["2018ZX09711001-007-002"]}]},{"name":"The Drug Innovation Major Project of China","award":["2017ZX09101001-007"],"award-info":[{"award-number":["2017ZX09101001-007"]}]},{"name":"CAMS Initiative for Innovative Medicine","award":["2017-I2M-1-012"],"award-info":[{"award-number":["2017-I2M-1-012"]}]}],"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":[[2019,11,14]]},"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:p>A multicomponent pharmaceutical salt formed by the isoquinoline alkaloid berberine (5,6-dihydro-9,10-dimethoxybenzo[<jats:italic>g<\/jats:italic>]-1,3-benzodioxolo[5,6-<jats:italic>a<\/jats:italic>]quinolizinium, BBR) and the nonsteroidal anti-inflammatory drug diclofenac {2-[2-(2,6-dichloroanilino)phenyl]acetic acid, DIC} was discovered. Five solvates of the pharmaceutical salt form were obtained by solid-form screening. These five multicomponent solvates are the dihydrate (BBR\u2013DIC\u00b72H<jats:sub>2<\/jats:sub>O or C<jats:sub>20<\/jats:sub>H<jats:sub>18<\/jats:sub>NO<jats:sub>4<\/jats:sub>\n                  <jats:sup>+<\/jats:sup>\u00b7C<jats:sub>14<\/jats:sub>H<jats:sub>10<\/jats:sub>Cl<jats:sub>2<\/jats:sub>NO<jats:sub>2<\/jats:sub>\n                  <jats:sup>\u2212<\/jats:sup>\u00b72H<jats:sub>2<\/jats:sub>O), the dichloromethane hemisolvate dihydrate (BBR\u2013DIC\u00b70.5CH<jats:sub>2<\/jats:sub>Cl<jats:sub>2<\/jats:sub>\u00b72H<jats:sub>2<\/jats:sub>O or C<jats:sub>20<\/jats:sub>H<jats:sub>18<\/jats:sub>NO<jats:sub>4<\/jats:sub>\n                  <jats:sup>+<\/jats:sup>\u00b7C<jats:sub>14<\/jats:sub>H<jats:sub>10<\/jats:sub>Cl<jats:sub>2<\/jats:sub>NO<jats:sub>2<\/jats:sub>\n                  <jats:sup>\u2212<\/jats:sup>\u00b70.5CH<jats:sub>2<\/jats:sub>Cl<jats:sub>2<\/jats:sub>\u00b72H<jats:sub>2<\/jats:sub>O), the ethanol monosolvate (BBR\u2013DIC\u00b7C<jats:sub>2<\/jats:sub>H<jats:sub>5<\/jats:sub>OH or C<jats:sub>20<\/jats:sub>H<jats:sub>18<\/jats:sub>NO<jats:sub>4<\/jats:sub>\n                  <jats:sup>+<\/jats:sup>\u00b7C<jats:sub>14<\/jats:sub>H<jats:sub>10<\/jats:sub>Cl<jats:sub>2<\/jats:sub>NO<jats:sub>2<\/jats:sub>\n                  <jats:sup>\u2212<\/jats:sup>\u00b7C<jats:sub>2<\/jats:sub>H<jats:sub>5<\/jats:sub>OH), the methanol monosolvate (BBR\u2013DIC\u00b7CH<jats:sub>3<\/jats:sub>OH or C<jats:sub>20<\/jats:sub>H<jats:sub>18<\/jats:sub>NO<jats:sub>4<\/jats:sub>\n                  <jats:sup>+<\/jats:sup>\u00b7C<jats:sub>14<\/jats:sub>H<jats:sub>10<\/jats:sub>Cl<jats:sub>2<\/jats:sub>NO<jats:sub>2<\/jats:sub>\n                  <jats:sup>\u2212<\/jats:sup>\u00b7CH<jats:sub>3<\/jats:sub>OH) and the methanol disolvate (BBR\u2013DIC\u00b72CH<jats:sub>3<\/jats:sub>OH or C<jats:sub>20<\/jats:sub>H<jats:sub>18<\/jats:sub>NO<jats:sub>4<\/jats:sub>\n                  <jats:sup>+<\/jats:sup>\u00b7C<jats:sub>14<\/jats:sub>H<jats:sub>10<\/jats:sub>Cl<jats:sub>2<\/jats:sub>NO<jats:sub>2<\/jats:sub>\n                  <jats:sup>\u2212<\/jats:sup>\u00b72CH<jats:sub>3<\/jats:sub>OH), and their crystal structures were determined. All five solvates of BBR\u2013DIC (1:1 molar ratio) were crystallized from different organic solvents. Solvent molecules in a pharmaceutical salt are essential components for the formation of crystalline structures and stabilization of the crystal lattices. These solvates have strong intermolecular O...H hydrogen bonds between the DIC anions and solvent molecules. The intermolecular hydrogen-bond interactions were visualized by two-dimensional fingerprint plots. All the multicomponent solvates contained intramolecular N\u2014H...O hydrogen bonds. Various \u03c0\u2013\u03c0 interactions dominate the packing structures of the solvates.<\/jats:p>","DOI":"10.1107\/s2053229619015432","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T13:44:03Z","timestamp":1574689443000},"page":"1644-1651","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":7,"title":["Five solvates of a multicomponent pharmaceutical salt formed by berberine and diclofenac"],"prefix":"10.1107","volume":"75","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhi","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"fp3076_bb1","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/anie.199515551","volume":"34","author":"Bernstein","year":"1995","journal-title":"Angew. 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