Viedma ripening is the attrition-induced spontaneous chiral amplification of a conglomerate crystal mixture. To demonstrate the general nature of this deracemization process, we have extended ...attrition-enhanced chiral amplification to 10 achiral organic molecules that form conglomerate chiral crystals: benzil (1), diphenyl disulfide (2), benzophenone (3), tetraphenylethylene (4), guanidine carbonate (5), butylated hydroxytoluene (6), hippuric acid (7), ninhydrin (8), cytosine (9), and adeninium dinitrate (10). In these experiments the time required to reach homochirality was as low as 3 h and typically ranged from 25 to 50 h. In most cases amplification to homochirality of both enantiomers was observed in repeat experiments, although often in a nonstochastic fashion, reflecting the scalemic nature of the starting material. We have also demonstrated the utility of quantitative circular dichroism (CD) to determine enantiomeric excess in systems where chirality exists only in the solid-state.
Rationale
Mobile‐phase additives in liquid chromatography/mass spectrometry (LC/MS) are used to improve peak shape, analyte ionization efficiency and method coverage. Both basic and acidic mobile ...phases have been used successfully for negative electrospray ionization (ESI), but very few systematic investigations exist to date to justify the choice of mobile phase. Acetic acid was previously shown to improve ionization in untargeted metabolomics of urine, but has not been investigated in lipidomics. The goal of this study was to systematically compare the performance of acetic acid to that of other commonly employed additives in negative LC/ESI‐MS lipidomics.
Methods
The performance of acetic acid was compared to that of commonly used mobile‐phase additives in lipidomics, namely ammonium acetate, ammonium acetate with acetic acid and ammonium hydroxide, using lipid standard solutions containing representatives of major mammalian lipid subclasses and isopropanol‐precipitated human plasma. This design allowed comparison of the influence of additive and additive concentration on lipid signal intensity, lipid peak shape and lipid coverage in both simple and complex biological matrices using both Orbitrap and quadrupole time‐of‐flight MS platforms with different ESI source designs.
Results
Ammonium hydroxide caused 2‐ to 1000‐fold signal suppression of all lipid classes in comparison to acetic acid. In comparison to ammonium acetate, acetic acid increased lipid signal intensity from 2‐ to 19‐fold for 11 lipid subclasses, and decreased ionization efficiency only for ceramide and phosphatidylcholine lipid classes which can be effectively ionized in positive ESI mode. The improved ionization efficiency using acetic acid also increased lipid coverage by 21–50% versus ammonium acetate additive.
Conclusions
Acetic acid at a concentration of 0.02% (v/v) is the suggested choice as a mobile‐phase additive for lipidomics and targeted lipid profiling with negative LC/ESI‐MS based on signal enhancement and improved lipid coverage compared to ammonium acetate, ammonium acetate with acetic acid and ammonium hydroxide mobile phases.
Oriented attachment, a nonclassical crystallization phenomenon, describes the spontaneous self-assembly of adjoining crystals with common crystallographic orientations. Introducing chiral recognition ...between crystals during oriented attachment enables enantiomer-specificity and the formation of homochiral structures. Herein, we report efficient enantiomer-specific oriented attachment for suspended crystals of guanidine carbonate to form mesoscale homochiral or enantioenriched aggregates under boiling or shaking conditions. These aggregates display polyhedral macrostructures and their chirality was monitored using circular dichroism and polarized light microscopy.
