Kinetic trapping of metastable amino acid polymorphs.
Second harmonic generation (SHG) microscopy measurements indicate that inkjet-printed racemic solutions of amino acids can produce nanocrystals trapped in metastable polymorph forms upon rapid solvent evaporation. Polymorphism impacts the composition, distribution, and physico-kinetic properties of organic solids, with energetic arguments favoring the most stable polymorph. In this study, unfavored noncentrosymmetric crystal forms were observed by SHG microscopy. Polarization-dependent SHG measurement and synchrotron X-ray microdiffraction analysis of individual printed drops are consistent with formation of homochiral crystal production. Fundamentally, these results provide evidence supporting the ubiquity of Ostwald's Rule of Stages, describing the hypothesized transitioning of crystals between metastable polymorphic forms in the early stages of crystal formation. Practically, the presence of homochiral metastable forms has implications on chiral resolution and on solid form preparations relying on rapid solvent evaporation.
Department of Chemistry, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.
Azhad U
AU
Chowdhury
Christopher M
CM
Dettmar
Shane Z
SZ
Sullivan
Shijie
S
Zhang
Kevin T
KT
Jacobs
David J
DJ
Kissick
Thora
T
Maltais
Hartmut G
HG
Hedderich
Patricia A
PA
Bishop
Garth J
GJ
Simpson
D000596:Amino Acids / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D007700:Kinetics; D018613:Microscopy, Confocal; D013237:Stereoisomerism; D013816:Thermodynamics
D000596:Amino Acids