{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:28:08Z","timestamp":1790342888250,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvian Council of Science","doi-asserted-by":"publisher","award":["lzp-2018\/1-0312"],"award-info":[{"award-number":["lzp-2018\/1-0312"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The arrangement of hydroxyl groups in the benzene ring has a significant effect on the propensity of dihydroxybenzoic acids (diOHBAs) to form different solid phases when crystallized from solution. All six diOHBAs were categorized into distinctive groups according to the solid phases obtained when crystallized from selected solvents. A combined study using crystal structure and molecule electrostatic potential surface analysis, as well as an exploration of molecular association in solution using spectroscopic methods and molecular dynamics simulations were used to determine the possible mechanism of how the location of the phenolic hydroxyl groups affect the diversity of solid phases formed by the diOHBAs. The crystal structure analysis showed that classical carboxylic acid homodimers and ring-like hydrogen bond motifs consisting of six diOHBA molecules are prominently present in almost all analyzed crystal structures. Both experimental spectroscopic investigations and molecular dynamics simulations indicated that the extent of intramolecular bonding between carboxyl and hydroxyl groups in solution has the most significant impact on the solid phases formed by the diOHBAs. Additionally, the extent of hydrogen bonding with solvent molecules and the mean lifetime of solute\u2013solvent associates formed by diOHBAs and 2-propanol were also investigated.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050734","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T02:31:34Z","timestamp":1621218694000},"page":"734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined Use of Structure Analysis, Studies of Molecular Association in Solution, and Molecular Modelling to Understand the Different Propensities of Dihydroxybenzoic Acids to Form Solid Phases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4285-0524","authenticated-orcid":false,"given":"Aija","family":"Trimdale","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, University of Latvia, Jelgavas iela 1, LV-1004 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9905-3257","authenticated-orcid":false,"given":"Anatoly","family":"Mishnev","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, Aizkraukles iela 21, LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-8971","authenticated-orcid":false,"given":"Agris","family":"B\u0113rzi\u0146\u0161","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Latvia, Jelgavas iela 1, LV-1004 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,16]]},"reference":[{"key":"ref_1","first-page":"8619","article-title":"Facts and fictions about polymorphism","volume":"49","author":"Bernstein","year":"2015","journal-title":"Chem. 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