3 research outputs found
Crystallographic Analysis of Phase Dissociation Related to Anomalous Solubility of Irsogladine Maleate
We report the anomalous
solubility of the pharmaceutical salt irsogladine
maleate, which is associated with phase dissociation. The anomalous
solubility was demonstrated by the similarity of solubility and miscibility
between the salt and its base in ethanol solvent. The phase dissociation
was revealed and confirmed by distinguishing irsogladine maleate and
its free base using single-crystal X-ray analysis. Herein, the crystal
structures of irsogladine maleate and its base were reported for the
first time, and the plausible mechanism for phase dissociation was
established based on the structural correlations between those phases
Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt–Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study
Dimenhydrinate
(DIM) is an important drug used for the prevention
of motion sickness. Surprisingly, the crystal structure of DIM has
not been determined over the last 67 years. In this study, we have
attempted to determine the structure of DIM through single crystal
X-ray structure analysis and confirmed the salt–cocrystal ambiguity.
Because of the existence of proton transfer, DIM exists as a salt
crystal. The crystal structure of DIM contains the anionic form of
8-chlorotheophylline whose existence was confirmed using density functional
theory calculation. Other solid-state characterizations based on spectroscopy
and thermal analysis were also conducted in order to fill the vacancy
regarding the solid-state characterization. Kinetic and intrinsic
solubility tests were also performed to evaluate the physicochemical
properties of DIM raw material
Interaction Analysis of FABP4 Inhibitors by X‑ray Crystallography and Fragment Molecular Orbital Analysis
X-ray crystal structural determination
of FABP4 in complex with
four inhibitors revealed the complex binding modes, and the resulting
observations led to improvement of the inhibitory potency of FABP4
inhibitors. However, the detailed structure–activity relationship
(SAR) could not be explained from these structural observations. For
a more detailed understanding of the interactions between FABP4 and
inhibitors, fragment molecular orbital analyses were performed. These
analyses revealed that the total interfragment interaction energies
of FABP4 and each inhibitor correlated with the ranking of the <i>K</i><sub>i</sub> value for the four inhibitors. Furthermore,
interactions between each inhibitor and amino acid residues in FABP4
were identified. The oxygen atom of Lys58 in FABP4 was found to be
very important for strong interactions with FABP4. These results might
provide useful information for the development of novel potent FABP4
inhibitors