ChiralityPub Date : 2026-04-06DOI: 10.1002/chir.70098
Emma A. Khachatryan, Anna F. Mkrtchyan, Anahit M. Hovhannisyan, Melanya Ghazaryan, Ashot S. Saghyan
{"title":"Asymmetric Synthesis and Antibacterial Evaluation of β-Substituted (S)-α-Alanine Analogs Containing a Piperazine Moiety in the Side Chain","authors":"Emma A. Khachatryan, Anna F. Mkrtchyan, Anahit M. Hovhannisyan, Melanya Ghazaryan, Ashot S. Saghyan","doi":"10.1002/chir.70098","DOIUrl":"10.1002/chir.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of novel enantiomerically enriched α-amino acids containing piperazine fragments were synthesized via nucleophilic addition of piperazine derivatives (<b>2a–d</b>) to the C = C bond of a square-planar Ni (II) complex of the Schiff base derived from dehydroalanine and the chiral auxiliary (<i>S</i>)-BPB (<b>1</b>). The reactions proceeded under basic catalysis and were thermodynamically controlled, affording the major (<i>S</i>,<i>S</i>)-diastereomers with high diastereomeric excess (88%–92%). Acid hydrolysis of the diastereomeric Ni (II) complexes, followed by ion-exchange purification and crystallization, yielded the corresponding α-amino acids (<b>4a–d</b>) with high enantiomeric purities (ee 95%–99%). The chiral auxiliary (<i>S</i>)-BPB was recovered in > 96% yield without loss of enantiomeric purity, demonstrating the method's efficiency and sustainability. The antibacterial activity of the synthesized α-amino acids (<b>4a–d</b>) was evaluated against selected Gram-positive and Gram-negative bacterial strains, including <i>Pseudomonas fluorescens</i> 9150, <i>Escherichia coli</i> DH5α, and <i>Staphylococcus aureus</i> MDC 5233, using the standard microdilution method. All tested compounds exhibited moderate antibacterial activity, with MIC values of approximately 5 mM against <i>E. coli</i> and <i>S. aureus</i>. Notably, compounds <b>4c</b> and <b>4d</b> demonstrated significantly enhanced activity against <i>P. fluorescens</i> 9150, with MIC values of 0.675 mM (corresponding to ~ 0.144 and ~ 0.168 mg/mL, respectively). These results indicate that structural modification of piperazine-containing α-amino acids can significantly influence their antibacterial properties and highlight this scaffold as a promising platform for the development of new antimicrobial agents.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthesis and Photophysical Properties of Chiral Diaminodicyanoquinodimethane: Formation Mechanism and Chiroptical Properties","authors":"Aslınur Gokpinar, Perihan Ozturk, Duygu Tan, Akın Akdag","doi":"10.1002/chir.70099","DOIUrl":"10.1002/chir.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>Chirality is fundamental to biological systems and the pharmaceutical industry, yet efficient methods for determining the absolute configuration of chiral compounds remain a challenge. This study reports the synthesis and characterization of chiral diaminodicyanoquinodimethane (DADQ) compounds derived from tetracyanoquinodimethane (TCNQ) and primary amines. Using a combination of NMR, UV-Vis, circular dichroism (CD) spectroscopy, and EPR, we elucidated the formation mechanism of these compounds and explored their optical properties. Furthermore, CD spectra showed a pattern that correlates with their configurations: DADQs with R configuration showed negative CD signals in methanol and DMSO, whereas DADQs with S configuration showed positive CD signals. The DADQs with aromatic side chains reversed their CD signals in relatively nonpolar solvents. These findings indicate that chirality can be effectively transferred from primary amines to DADQ, offering a potential method for determining the absolute configurations of primary amines. The results highlight the promise of chiral DADQ compounds in chiroptical applications and their utility in elucidating the chirality of biologically relevant molecules.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-04-01DOI: 10.1002/chir.70097
Xiaozhen Shao, Guangfu Xu, Jiaquan Chen, Ke Yang, Yingxiang Du, Tao Yu
{"title":"Cyclodextrin Metal–Organic Framework With Amino Acid Chiral Ligands for Capillary Electrochromatographic Enantioseparation","authors":"Xiaozhen Shao, Guangfu Xu, Jiaquan Chen, Ke Yang, Yingxiang Du, Tao Yu","doi":"10.1002/chir.70097","DOIUrl":"10.1002/chir.70097","url":null,"abstract":"<div>\u0000 \u0000 <p>Metal–organic frameworks (MOFs) are widely used in the field of chromatographic separation due to their unique properties. A vapor diffusion method was used to synthesize the cyclodextrin MOF (CD-MOF) with D-histidine (D-His) as a chiral ligand (D-His-<i>γ</i>-CD-MOF), which was applied to capillary electrochromatography (CEC). D-His-<i>γ</i>-CD-MOF was characterized by X-ray diffractometer (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), and thermogravimetric analyzer (TGA). This CEC system achieved baseline separation of three chiral drugs under optimal separation conditions. In addition, this CEC system was evaluated for repeatability using salbutamol as a model drug and the results showed that this system had good repeatability. Additionally, the chiral separation mechanism of the CEC system was discussed through adsorption kinetic experiments, adsorption isotherm experiments, and adsorption thermodynamic experiments.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-03-30DOI: 10.1002/chir.70096
Mayra A. Martínez-Torres, Antonio J. Oliveros-Ortiz, Ana K. Villagómez-Guzmán, Armando Talavera-Alemán, Gerardo Rosas, Tzasna Hernández-Delgado, David Morales-Morales, Rosa E. del Río, Mario A. Gómez-Hurtado, Gabriela Rodríguez-García
{"title":"Chiral Organometallic Atropoisomers of the Type [Ru(η6-p-cymene)(κ2-diterpene)Cl] Induced by Natural Kaurenoic and Beyerenoic Acids","authors":"Mayra A. Martínez-Torres, Antonio J. Oliveros-Ortiz, Ana K. Villagómez-Guzmán, Armando Talavera-Alemán, Gerardo Rosas, Tzasna Hernández-Delgado, David Morales-Morales, Rosa E. del Río, Mario A. Gómez-Hurtado, Gabriela Rodríguez-García","doi":"10.1002/chir.70096","DOIUrl":"10.1002/chir.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>Chirality is an interesting property in molecules with a plethora of potential applications. In this line, due to their origin, most chiral natural compounds can be considered enantiopure, and many of these molecules include interesting functional groups that can be of interest in both coordination and organometallic chemistry to obtain chiral coordinated and/or organometallic compounds. And most importantly, these molecules may thus confer chiral properties into their metal complexes. Therefore, in this work, we show the use of kaurenoic (<b>1</b>) and beyerenoic (<b>2</b>) acids as efficient ligands to obtain the corresponding organometallic Ru(II) complexes by using [(<i>η</i><sup>6</sup>-<i>p</i>-cymene)Ru(<i>μ</i>-Cl)Cl]<sub>2</sub> as starting material by a simple procedure reacting the corresponding sodium salts of <b>1</b> and <b>2</b> (<b>1a</b> and <b>2a</b>) with [(<i>η</i><sup>6</sup>-<i>p</i>-cymene)Ru(<i>μ</i>-Cl)Cl]<sub>2</sub> in an 2:1 M ratio to yield the corresponding (<i>S</i>a)-[Ru(<i>η</i><sup>6</sup>-<i>p</i>-cymene)(<i>κ</i><sup><i>2</i></sup>-beyerenate)Cl] (<b>3</b>) and (<i>S</i>a)-[Ru(<i>η</i><sup>6</sup>-<i>p</i>-cymene)(<i>κ</i><sup><i>2</i></sup>-kaurenate)Cl] (<b>4</b>) derivatives. Both complexes were fully characterized by common spectroscopic techniques and their structures unequivocally determined by single crystal X-ray diffraction analysis. In addition, the chirality of both organometallic compounds was analyzed by electronic circular dichroism techniques as well as by <i>in silico</i> methods. Antimicrobial assays were boarded demonstrating slight antifungal activity. The results not only confirm the conferring of chirality by the ligands to their organometallic derivatives but also open a window for their future potential applications as, for example, potential chiral catalysts or as metallodrugs in the battle against diseases of global concern as well optimistically inspiring the potential use of other natural products as ligands with a wide number of applications.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-03-24DOI: 10.1002/chir.70095
A. R. Priyadharshni, Jony Susanna Kandula, Dayasagar Rajiv Karkile, Kale Shyam Shirishkumar, Keyur Parmar, P. Radhakrishnanand
{"title":"Enantioselective Chiral Separation and Quantitation of PI3Kγ Inhibitor Eganelisib in Rat Plasma Using UHPLC–MS/MS: Application to Evaluate Pharmacokinetic Study","authors":"A. R. Priyadharshni, Jony Susanna Kandula, Dayasagar Rajiv Karkile, Kale Shyam Shirishkumar, Keyur Parmar, P. Radhakrishnanand","doi":"10.1002/chir.70095","DOIUrl":"10.1002/chir.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>Eganelisib (EGN, IPI-549), an investigational new drug, is a potent first-in-class PI3Kγ inhibitor with high selectivity compared to other class I PI3K isoforms, with one asymmetric center. Enantiomers have similar physicochemical properties but differ in their biological characteristics, like absorption, distribution, metabolism, and excretion. Hence, a suitable analytical approach is required to investigate the enantioselective behavior in ADME-Tox. In the current study, a sensitive, reliable, and precise chiral LC–MS/MS method has been developed for quantifying EGN enantiomers in rat plasma, in accordance with USFDA guidelines. Enantiomeric separation was achieved within 15 min on a Chiralpak-IK-3 (250 × 4.6 mm, 3 μm) immobilized polysaccharide column, containing 10 mM ammonium bicarbonate and a premixed mixture of acetonitrile and methanol (80:20 v/v) as the mobile phase in the ratio of 10:90 (v/v), with isocratic elution at a flow rate of 0.6 mL/min. Multiple reaction monitoring (MRM) mode was used to detect EGN and SOF in positive electrospray ionization (ESI) mode, characterized by their transitions at m/z 529.3→326.3, 161.1, and m/z 465.1→447.1, 270.2, 252.1. The method demonstrated a linear response in the range of 1–600 ng/mL for both enantiomers, with a lower limit of quantification of 1 ng/mL. The validated bioanalytical method was applied to evaluate the enantioselective pharmacokinetics of EGN enantiomers in rat plasma for the first time, utilizing a model-independent approach. The (<i>R</i>)-enantiomer showed relative fold differences in <i>C</i><sub>max</sub>, <i>t</i><sub>1/2</sub>, AUC<sub>0-<i>t</i></sub>, and AUC<sub>0-∞</sub> when compared to the (<i>S</i>)-enantiomer, indicating the enantioselective behavior of EGN enantiomers.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-03-20DOI: 10.1002/chir.70094
Sakine Atila Karaca, Sona Aliyeva, Duygu Yeniceli
{"title":"A Design of Experiments-Based Chiral HPLC Method for the Quantification of Talazoparib and Enantiomeric Purity Determination in Pharmaceutical Formulations","authors":"Sakine Atila Karaca, Sona Aliyeva, Duygu Yeniceli","doi":"10.1002/chir.70094","DOIUrl":"10.1002/chir.70094","url":null,"abstract":"<p>Talazoparib is an oral inhibitor of the polyadenosine 5′-diphosphoribose polymerase enzymes used for the treatment of adults with deleterious or suspected deleterious germline <i>BRCA</i>-mutated, human epidermal growth factor receptor 2-negative, locally advanced, or metastatic breast cancer. A novel chiral HPLC method was proposed for the enantiomeric separation and quantification of talazoparib. Chiral separation was performed in a reversed-phase mode on a Chiralpak IC (4.6 × 250 mm, 5 μm) column using a simple mobile phase consisting of 0.2% perchloric acid in water:acetonitrile (60:40, v/v). A Box–Behnken design was used for the optimization of chromatographic parameters, and the enantiomeric separation was obtained within 12 min with a resolution value exceeding 7.7. The method was validated with respect to specificity, linearity, accuracy, precision, and robustness. The accuracy and precision of the method were satisfactory, with intraday and interday recovery values of 98%–102% and relative standard deviation values less than 2%. The method was used for the enantiomeric purity control of talazoparib in pharmaceutical formulations, which is crucial for patient safety and therapeutic efficacy.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-03-12DOI: 10.1002/chir.70093
Xinxin Ling, Lifeng Tan
{"title":"Enantiomers of Ruthenium(II) Complex [Ru(bpy)2(qip)]2+ Exhibit Highly Chiral-Selective Effects on the Stabilization of Third Strand of Triplex RNA Poly(U-A*U)","authors":"Xinxin Ling, Lifeng Tan","doi":"10.1002/chir.70093","DOIUrl":"10.1002/chir.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Two chiral Ru(II) complexes bearing a quinoline ring, Λ-[Ru(bpy)<sub>2</sub>(qip)]<sup>2+</sup> (Λ-<b>1</b>) and Δ-[Ru(bpy)<sub>2</sub>(qip)]<sup>2+</sup> (Δ-<b>1</b>, 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-<b>1</b> demonstrating a stronger binding affinity for triplex RNA than Λ-<b>1</b>. Luminescence titration experiments further supported the binding of the complexes via intercalation. CD analysis demonstrated that both Λ-<b>1</b> and Δ-<b>1</b> 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.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-03-05DOI: 10.1002/chir.70092
Lei Yue, Kaylee Quick, Adam Beard, Anne Liao
{"title":"Evaluation of Acetonitrile in Combination With Alcohols as Modifiers in Chiral Supercritical Fluid Chromatography","authors":"Lei Yue, Kaylee Quick, Adam Beard, Anne Liao","doi":"10.1002/chir.70092","DOIUrl":"10.1002/chir.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>This study systematically investigated the effect of acetonitrile (ACN) in combination with alcohols as modifiers for chiral supercritical fluid chromatography (SFC) separations. The elution profiles of nine internal samples were evaluated using various ratios of ACN/methanol (MeOH) mixtures as the modifiers on four chiral columns. Eighty-three percent of the retention factors (k′) exhibited an initial decrease followed by an upward trend as the ACN percentage increased, likely reflecting changes in hydrogen-bonding, dipole–dipole, and π–π interaction sites on the chiral stationary phases (CSPs). A broader set of compounds, including those with two and four isomers, was further screened using four different ACN/alcohol ratios (2:8, 5:5, 7:3, and 8:2). Compared to pure alcohol modifiers, the ACN/alcohol mixtures demonstrated complementary chiral recognition for compounds with two isomers, resulting in improved and unique separations. For some four-isomer compounds, ACN/alcohol mixtures resolved more isomers than pure alcohols. Additionally, adding 20% ACN to the MeOH modifier significantly improved productivity for late-eluting compounds by reducing cycle time, sharpening peak shape, and decreasing system pressure due to its lower viscosity.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Asymmetric Homogeneous Oxidation Reactions Catalyzed by First-Row Transition Metal Complexes","authors":"Geeta Devi Yadav, Deepa Uppal, Priyanka Jhajharia, Balaram Pani, Surendra Singh","doi":"10.1002/chir.70090","DOIUrl":"10.1002/chir.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>Asymmetric homogeneous oxidation reactions catalyzed by first-row transition metal complexes have been summarized, focusing on the performance of the chiral catalyst and its relation with the key factors (structure of the chiral ligands, type of metal, solvent, temperature, and oxidant) in the catalytic systems. A variety of oxidants, including hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), molecular oxygen (O<sub>2</sub>), sodium hypochlorite (NaOCl), <i>tert</i>-butyl hydroperoxide (TBHP), and iodosylbenzene (PhIO), have been employed for the oxidation reactions using different chiral transition metal complexes. This review is mainly focused on the reports of various asymmetric metal complexes as homogeneous catalysts derived from first-row transition metals and chiral ligands for a range of oxidation reactions, such as epoxidation of olefins and <i>α,β</i>-unsaturated carbonyl compounds, sulfoxidation, hydroxylation, dihydroxylation, and oxidation of spirocyclic compounds. Several chiral ligands and their metal complexes (including metals titanium, chromium, manganese, iron, cobalt, and vanadium) are utilized in asymmetric oxidation reactions, whereas asymmetric manganese complexes have been extensively used for epoxidation, hydroxylation, and oxidative kinetic resolution. This review provides a clear and broad perception for better recognizing the homogeneous asymmetric catalysts used in oxidation reactions.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChiralityPub Date : 2026-03-04DOI: 10.1002/chir.70087
Caterina Momoli, Laura Palombi, Isabella Daidone, Erica Scarel, Massimiliano Aschi
{"title":"Resolution of a Chiral β-Aminoketone via Diastereomeric Salt Formation: From Experimental Evidence to Molecular-Level Insights Into Solution-Phase Clusters","authors":"Caterina Momoli, Laura Palombi, Isabella Daidone, Erica Scarel, Massimiliano Aschi","doi":"10.1002/chir.70087","DOIUrl":"10.1002/chir.70087","url":null,"abstract":"<p>The classical diastereomeric salt resolution approach was employed to separate (±)-1,3-diphenyl-3-(phenylamino)propan-1-one using both enantiomers of 10-camphorsulfonic acid (CSA) as resolving agents. Gentle stirring at room temperature resulted in the stereoselective precipitation of a single diastereomeric salt, yielding a solid phase highly enriched in one enantiomer of the target compound. Control experiments confirmed the crucial role of the chiral counterion in directing the selectivity of the process. Molecular Dynamics simulations and subsequent Principal Component Analysis revealed slight but significant differences in the pre-nucleation size distribution of ionic clusters and in the dynamics of their mutual interconversion, hence suggesting that these differences could play a role in the racemic resolution.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"38 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}