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Efficient screening for ternary molecular ionic cocrystals using a complementary mechanosynthesis and computational structure prediction approach
- Source :
- Chemistry (Weinheim an Der Bergstrasse, Germany)
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- The discovery of molecular ionic cocrystals (ICCs) of active pharmaceutical ingredients (APIs) widens the opportunities for optimizing the physicochemical properties of APIs whilst facilitating the delivery of multiple therapeutic agents. However, ICCs are often observed serendipitously in crystallization screens and the factors dictating their crystallization are poorly understood. We demonstrate here that mechanochemical ball milling is a versatile technique for the reproducible synthesis of ternary molecular ICCs in less than 30 min of grinding with or without solvent. Computational crystal structure prediction (CSP) calculations have been performed on ternary molecular ICCs for the first time and the observed crystal structures of all the ICCs were correctly predicted. Periodic dispersion‐corrected DFT calculations revealed that all the ICCs are thermodynamically stable (mean stabilization energy=−2 kJ mol−1) relative to the crystallization of a physical mixture of the binary salt and acid. The results suggest that a combined mechanosynthesis and CSP approach could be used to target the synthesis of higher‐order molecular ICCs with functional properties.<br />Spot on predictions! The mechanosynthesis of ternary molecular ionic cocrystals (ICCs) with significantly different physicochemical properties has been achieved in less than 30 min of grinding. The crystal structures of the ICCs were successfully predicted by using computational methods. The results pave the way for the efficient screening of higher‐order multicomponent crystal forms with functional properties (see figure).
- Subjects :
- Chemistry, Multidisciplinary
Ionic bonding
SOLID-STATE LANDSCAPE
Crystal structure
010402 general chemistry
Crystal engineering
01 natural sciences
POTENTIAL-FUNCTION MODELS
Catalysis
crystal structure prediction
law.invention
ENERGY
Computational chemistry
law
Crystallization
mechanosynthesis
CO-CRYSTALS
SUPRAMOLECULAR SYNTHONS
Science & Technology
Full Paper
STABILITY
010405 organic chemistry
Chemistry
green chemistry
Organic Chemistry
SALT
DISTRIBUTED MULTIPOLE ANALYSIS
General Chemistry
Full Papers
PHARMACEUTICAL COCRYSTALS
0104 chemical sciences
Crystal structure prediction
X-ray diffraction
crystal engineering
X-ray crystallography
Physical Sciences
CRYSTAL-STRUCTURE PREDICTION
Mechanosynthesis
molecular ionic cocrystals
Ternary operation
03 Chemical Sciences
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Chemistry (Weinheim an Der Bergstrasse, Germany)
- Accession number :
- edsair.doi.dedup.....86259a8955d98298a1fb1458107ce25c