title: "Predicting" Polymorphs of Pharmaceuticals Using Hydrogen Bond Propensities: Probenecid and Its Two Single-Crystal-to-Single-Crystal Phase Transitions.
abstract: The recently developed hydrogen-bonding propensity tool in the Cambridge Structural Database software package (Mercury) was tested to predict polymorphs. The compounds for the study were chosen from a list of approximately 300 pharmaceutically important compounds, for which multiple crystal forms had not been previously reported. The hydrogen-bonding propensity analysis was carried out on approximately 60 randomly selected compounds from this list. Several compounds with a high probability for exhibiting polymorphism in the analysis were chosen for a limited experimental crystal form screening. One of the compounds, probenecid, did not yield polymorphs by traditional solution crystallization screening, but differential scanning calorimetry revealed three polymorphs. All of them exhibit the same hydrogen bonding and transform via two reversible single-crystal-to single-crystal transformations, which have been characterized in detail through three single-crystal structure determinations at appropriate temperatures.
authors.affiliation: Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nauha
authors.affiliation: Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. Electronic address: joel.bernstein@nyu.edu.
authors.forename: Joel
authors.initials: J
authors.lastname: Bernstein
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D044367:Phase Transition; D011339:Probenecid / Q000737:chemistry*; D012984:Software
chemical_list: D000277:Adjuvants, Pharmaceutic; D011339:Probenecid
keywords: crystal engineering; crystal polymorphism; crystal structure; crystallization; crystallography; hydrates/solvates