The two-dimensional crystallization and on-surface chemistry of chiral polycyclic aromatic hydrocarbons provide access to surface-confined symmetry breaking and novel covalently bonded nanostructures. Here, we investigate the self-assembly of racemic 2,3-dicarbonitrile tetrahelicene on Ag(111). Using low-temperature scanning tunneling microscopy in combination with density functional theory calculations, we resolve the evolution of molecular organization as a function of coverage. After room-temperature deposition at submonolayer coverage, the tetrahelicene moiety spontaneously resolves into extended homochiral Kagomé domains upon cooling. The resulting monolayer consists of hexameric dimer motifs arranged in a porous network. These mirror-related supramolecular enantiomorphs are characteristic of two-dimensional conglomerate crystallization. As the surface coverage increases, the system undergoes a transition toward denser packing. At saturation, compact domains form that retains long-range lattice order while exhibiting a regular yet enantiomerically unbalanced distribution of both handednesses. The nonrandom incorporation of enantiomers distinguishes this phase from a racemic solid solution and instead indicates a compositionally biased, structurally ordered mixed phase.

Chirality plays a fundamental role in chemistry, biology, and materials science, where molecular activity and performance often depend on enantiomeric purity. However, most synthetic methods produce racemic mixtures, making efficient strategies for enantioseparation and chiral amplification essential. Among the available approaches, crystallization-based methods offer scalable and mechanistically versatile routes for controlling chirality in the solid state. This review summarizes recent advances in solid-state crystallization strategies for chiral resolution, chirality generation, and enantiomeric amplification. Emphasis is placed on the structural and thermodynamic factors governing the formation of racemic compounds, conglomerates, and solid solutions, and how these phase behaviors influence separation outcomes. Key methodologies including preferential crystallization, attrition-enhanced deracemization, and multicomponent crystallization via diastereomeric salts and chiral co-crystals are discussed to illustrate how rational control of intermolecular interactions and phase equilibria enables effective enantioseparation. Emerging insights into supramolecular symmetry breaking and confinement-driven chiral amplification are also highlighted, demonstrating that solid-state processes can generate or amplify chirality even from achiral precursors. By integrating representative examples with broader conceptual analysis, this review outlines key design principles governing chiral outcomes in crystalline systems and highlights expanding applications of chiral co-crystals in pharmaceuticals and as functional materials, providing a framework for future advances in crystallization-mediated chirality control.

Two chiral Ru(II) complexes bearing a quinoline ring, Λ-[Ru(bpy)2(qip)]2+ (Λ-1) and Δ-[Ru(bpy)2(qip)]2+ (Δ-1, where bpy = 2,2'-bipyridine and qip = 2-(quinolin-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline), were prepared. Their interactions with triplex RNA were systematically investigated using ultraviolet-visible (UV-Vis) spectroscopy, luminescence spectroscopy, nucleic acid thermal denaturation experiments, and circular dichroism (CD) spectroscopy. The data from UV-Vis titrations support intercalation as the binding mode for both enantiomers with triplex RNA. Further quantitative analysis revealed that the complexes exhibited significant chiral selectivity, with Δ-1 demonstrating a stronger binding affinity for triplex RNA than Λ-1. Luminescence titration experiments further supported the binding of the complexes via intercalation. CD analysis demonstrated that both Λ-1 and Δ-1 could significantly induce conformational changes in the triplex RNA, and strong intermolecular interactions between the complexes and triplex RNA were observed, further suggesting a potential intercalative binding mode. The thermal denaturation results revealed that the third strand was selectively and markedly stabilized. The stabilization of the third strand in the triplex RNA was significantly enhanced by both enantiomers, while exerting negligible effects on the template duplex. The chiral ruthenium(II) complex developed in this study exhibits specific stabilization of triplex RNA, providing an effective strategy for stabilizing triplex RNA structures.

Doenjang is the most used fermented soy product in Asian countries. At present, the simultaneous determination of DL-amino acids and histamine in doenjang has not been reported. Therefore, an UHPLC-MS/MS method was developed based on a novel chiral derivatization probe DBD-M-Pro, enabling for the first time the simultaneous quantification of 10 DL-amino acids and histamine in doenjang samples from different regions. Achieving resolution (Rs) values of 1.62-6.31 for the 10 DL-amino acids. The limits of detection (LODs) for DL-amino acids and histamine ranged from 0.54 to 15.62 pmol. The intraday and interday precision (RSD) were 0.21%-10.63%, and the average recoveries were 93.18%-109.07%. This method was applied to analyze 12 doenjang samples from Northeastern China, Korea, and Japan. The results showed that there was a significant geographical distribution of DL-amino acids and histamine. Yanbian Korean doenjang from China showed a unique advantage in that the total amount of DL-amino acids was significantly higher than that from other regions, with histamine concentration generally increasing with longer fermentation times. This study provides a stable and reliable method for the simultaneous determination of chiral amino acids and histamine in fermented foods such as doenjang.

ABSTRACTThe formation of salts remains a highly sought‐after yet unpredictable strategy for resolving chiral drugs. Using a drug–drug approach, we have investigated the crystallization behavior of Mefloquine (Mf), a racemic antimalarial drug, in combination with enantiopure (S)‐ibuprofen and (S)‐ketoprofen, as well as their racemic forms. Double salts and racemates have been obtained and characterized by single‐crystal and powder X‐ray diffraction, Hirshfeld surface analysis, thermal analysis (DSC and TGA), and solubility measurements. Structural analysis reveals that the formation of double salts often follows a pattern similar to the packing and supramolecular motifs found in the corresponding racemates. For the ketoprofen systems, the double salt and racemate have been found to be isostructural and isomorphic, whereas the ibuprofen systems display different architectures despite similar unit cells. Both double salts exhibited thermal stability and solubility profiles comparable to their racemic counterparts. On the other hand, the racemate with ketoprofen and the double salt with ibuprofen are the most soluble structures, suggesting that they are more stable systems than their counterparts. These findings support the view that double salt formation in such systems results from structural mimicry of racemates, emphasizing the challenges of predictable enantiomeric resolution and the importance of understanding structure–property relationships in chiral crystallization.

No abstract is available for this article.

The objective of this study was to investigate the biotransformation characteristics and stereoselective pharmacokinetic profiles of ibuprofen (IBU) enantiomers following administration of single isomers or a racemic mixture in rats, mice, and guinea pigs. A chiral LC-MS/MS method was employed to simultaneously determine (R)-(-)-ibuprofen and (S)-(+)-ibuprofen in trace whole blood samples (5 μL). Enantiomeric inversion of IBU was assessed after separate administration of single isomers or the racemic mixture, and pharmacokinetic parameters were calculated. Results demonstrated significantly higher AUClast values for the S-enantiomer compared to the R-enantiomer. Unidirectional enantiomeric inversion from R-IBU to S-IBU was observed in all tested species (rats, mice, and guinea pigs), with no reverse conversion detected. Notably, this study is the first to confirm strictly unidirectional enantiomeric inversion of IBU in guinea pigs. Conversion rates calculated from R-IBU and S-IBU concentrations following racemic IBU administration exhibited significant interspecies differences: 54.9 ± 5.6% (rats), 76.6 ± 5.3% (mice), and 65.6 ± 6.7% (guinea pigs). In contrast, no significant species differences were observed when conversion rates were derived from S-IBU concentrations after administration of individual enantiomers (R-IBU and S-IBU), yielding values of 65.9 ± 6.5%, 76.8 ± 21.2%, and 66.3 ± 14.4% for rats, mice, and guinea pigs, respectively.

ABSTRACTChiral flavonoids are frequently encountered in natural products consumed as food or therapeutic products. However, the taste and other bioactivities of stereoisomers are known to differ. Hence, stereoseparation methods are necessary to resolve these isomers, whether to measure stereoisomeric ratios or to purify individual stereoisomers for activity testing. In this study, we looked for the best conditions to resolve different families of chiral flavonoids, including auronols, flavanonols, aglycon, and glycosylated flavanones. Furthermore, we aimed to include this stereoseparation as the second‐dimension method in a two‐dimensional supercritical fluid chromatography system (SFC‐SFC), to achieve the resolution of chiral flavonoids in complex samples. First, a set of 10 standards of chiral flavonoids was examined on 5 immobilized polysaccharide chiral stationary phases. With the help of Derringer desirability functions, the columns offering the best options for rapid resolution were identified. Then, a sample of honey was analyzed in an SFC‐SFC system in heart‐cutting mode. The first‐dimension achiral separation resolved the complex mixture of honey and isolated the fraction of pinocembrin enantiomers, which were re‐analyzed in the second‐dimension chiral separation to measure the enantiomeric excess, and resolve co‐eluting isobaric species. This experiment demonstrates the relevance of this strategy in the resolution of flavonoid enantiomers from complex samples.