TY - JOUR
T1 - Hydrogen-Bond Synthon Preferences in Cocrystals of Acetazolamide
AU - Meers, Kaylen J.
AU - Tran, Thien Nhan
AU - Zheng, Qixuan
AU - Unruh, Daniel K.
AU - Hutchins, Kristin M.
N1 - Funding Information:
K.M.H. gratefully acknowledges financial support from Texas Tech University. K.J.M. gratefully acknowledges financial support from the Texas Tech University Honors College. The NMR instrument used for characterization was purchased with funds granted from National Science Foundation Grant No. CHE-1048553.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/8/5
Y1 - 2020/8/5
N2 - Acetazolamide (ACZ) is an active pharmaceutical ingredient with three main functional groups that can participate in a variety of hydrogen bond interactions. Here, we describe a series of cocrystals incorporating ACZ and cocrystal formers (CCFs) containing only aromatic nitrogen acceptor sites. We demonstrate one cocrystal wherein the CCF engages with ACZ at both of its hydrogen-bond donor sites, a behavior not commonly observed in ACZ cocrystals. We expand to include CCFs containing acceptor and donor moieties, and perform pKa calculations for ACZ, CCFs in this work, and previously reported pyridine-based CCF-ACZ cocrystals. Finally, we discuss pKa values, basicity, and geometric complementarity as methods for predicting synthon formation in ACZ cocrystals.
AB - Acetazolamide (ACZ) is an active pharmaceutical ingredient with three main functional groups that can participate in a variety of hydrogen bond interactions. Here, we describe a series of cocrystals incorporating ACZ and cocrystal formers (CCFs) containing only aromatic nitrogen acceptor sites. We demonstrate one cocrystal wherein the CCF engages with ACZ at both of its hydrogen-bond donor sites, a behavior not commonly observed in ACZ cocrystals. We expand to include CCFs containing acceptor and donor moieties, and perform pKa calculations for ACZ, CCFs in this work, and previously reported pyridine-based CCF-ACZ cocrystals. Finally, we discuss pKa values, basicity, and geometric complementarity as methods for predicting synthon formation in ACZ cocrystals.
UR - http://www.scopus.com/inward/record.url?scp=85090020814&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.0c00210
DO - 10.1021/acs.cgd.0c00210
M3 - Article
AN - SCOPUS:85090020814
VL - 20
SP - 5048
EP - 5060
JO - Crystal Growth and Design
JF - Crystal Growth and Design
SN - 1528-7483
IS - 8
ER -