Chirality最新文献

{"title":"Tandem Mass Spectrometry Approaches for Differentiation and Quantification Pidotimod and Its Three Isomers in the Gas Phase","authors":"Caiyu Zhang,&nbsp;Yang Liu,&nbsp;Lan He,&nbsp;Wei Li","doi":"10.1002/chir.23699","DOIUrl":"10.1002/chir.23699","url":null,"abstract":"<div>\u0000 \u0000 <p>Pidotimod is a chiral drug that possesses two chiral centers, resulting in three isomeric impurities (analytes, A). This study employs electrospray ionization ion trap mass spectrometry (ESI-MS) through collision-induced dissociation (CID) to investigate the chiral recognition of pidotimod and its three isomers to eliminate chromatographic separation. Three approaches were explored: (1) Protonated molecules in CID exhibited discriminative potential for diastereomers, with the ability to distinguish between <i>S,S</i> and <i>R,R</i> configurations, albeit with an <i>R</i>_{<i>chiral</i>} value of ~1.8. However, differentiation between <i>R,S</i> and <i>S,R</i> configurations was not achievable. (2) Alkali adductions (lithium and sodium) only discerned diastereomers. The <i>R</i>_{<i>chiral</i>} values of the diastereomers obtained from alkali adduct ions were significantly lower than those obtained from protonated ions. (3) Therefore, a third approach was used to address the challenge of distinguishing between <i>R,S</i> and <i>S,R</i> configurations, including the introduction of chiral references (ref) and transition metals (M^II) to form metal-bound complexes [M^II(A)(ref)-H]⁺. Additionally, we synthesized a novel ligand, 4-(N-tert-butoxycarbonyl [Boc]-L-prolinamido)phenol (denoted as ligand A), by modifying N-t-Boc-L-Pro with 2-aminophenol, which, in combination with Cu^II and Ni^II, enabled simultaneous differentiation of all four isomers. Cu^II complexes exhibited significant chiral selectivity between <i>R,S</i> and <i>S,R</i> configurations. Density functional theory calculations were performed to further elucidate the stereodynamic behavior and stoichiometry of these ions in the gas phase. These calculations revealed the interaction energy and coordination sites of the precursor ions in the gas phase, correlating well with MS/MS experiment results. Additionally, the logarithm of the Cu^II complexes' characteristic fragment ion abundance ratio demonstrated a strong linear relationship with enantiomeric excess (<i>ee</i>). This study presents a novel strategy for chiral drug quality control that eliminates chromatographic separation.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733671","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":"The Development of One New Normal Phase Liquid Chromatography Method and Thermodynamic Investigation of Olodaterol Hydrochloride Enantiomer","authors":"Wanbing Rao,&nbsp;Chenxia Zhang,&nbsp;Baolei Luan,&nbsp;Zhongqing Wang,&nbsp;Meiyan Qiu,&nbsp;Shaoyu Cai","doi":"10.1002/chir.23704","DOIUrl":"10.1002/chir.23704","url":null,"abstract":"<div>\u0000 \u0000 <p>In order to improve and replace the enantiomer method outlined in the olodaterol hydrochloride draft monograph (From the European Pharmacopoeia forum), one new, simple, and fast enantioselective normal phase high-performance liquid chromatography chiral method was developed on polysaccharide-based Chiral MX (2) (4.6 × 250 mm, 5 μm) column. n-Hexane, ethanol, and diethylamine in the ratio of 40:60:0.1 (V/V/V) were selected as mobile phase at a flow rate of 0.8 mL/min, and the detection was performed on a photodiode array detector at 225 nm with 5 μL injection volume. The column temperature was set at 40°C for better peak shape and sensitivity. The analysis time can be shortened to 15 min, whereas the resolution between enantiomer and olodaterol was found to be even more than 10.0, which was far better than that obtained with the reported method in this draft monograph. The developed chiral method was validated in accordance with ICH Q2 (R1), including specificity, LOD&amp;LOQ, precision, linearity, accuracy, and robustness. Thereby, the proposed method was demonstrated to be suitable for the determination of enantiomer in olodaterol hydrochloride bulk drug and drug product. Besides, the thermodynamic parameters were evaluated on the basis of Van't Hoff plots that was used to explain correlative chiral recognition mechanisms with the chiral stationary phase.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733672","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":"Study of the Enantioselectivity and Recognition Mechanism of Allyl-β-CD Modified Organic Polymer Monolithic Capillary Column","authors":"Chaoheng Jia,&nbsp;Futao Li,&nbsp;Anqi Li,&nbsp;Qiwen Li,&nbsp;Lu Huang","doi":"10.1002/chir.23697","DOIUrl":"10.1002/chir.23697","url":null,"abstract":"<div>\u0000 \u0000 <p>Allyl-β-CD was synthesized and used as the chiral functional monomer to prepare chiral organic polymer monolithic columns in capillary HPLC. First, the enantioselectivity of the prepared allyl-β-CD modified organic polymer monolithic capillary columns was investigated. Then, the influences of enantioseparation conditions of chiral drugs were further explored. Finally, the recognition mechanism was studied by molecular docking with AutoDock. Complete enantioseparations of four chiral drugs as well as partial enantioseparations of eight chiral drugs have been achieved. Results showed that the RSD values for run-to-run, day-to-day, and column-to-column variations ranged from 1.2% to 4.6%, 1.4% to 4.7%, and 2.0% to 6.1%, respectively. The enantioselectivity factor rather than resolution is correlated with the binding free energy difference between enantiomers with allyl-β-CD. Furthermore, the abundant ether bonds, hydroxyl groups, and hydrophobic cavities in cyclodextrin are responsible for the enantioseparation ability of the chiral monolithic capillary columns.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562746","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":"Expanding the Role of Chiral Drugs and Chiral Nanomaterials as a Potential Therapeutic Tool","authors":"Sourabh Satapathy,&nbsp;Shivam Kumar,&nbsp;Balak Das Kurmi,&nbsp;Ghanshyam Das Gupta,&nbsp;Preeti Patel","doi":"10.1002/chir.23698","DOIUrl":"10.1002/chir.23698","url":null,"abstract":"<div>\u0000 \u0000 <p>Chirality, the property of molecules having mirror-image forms, plays a crucial role in pharmaceutical and biomedical research. This review highlights its growing importance, emphasizing how chiral drugs and nanomaterials impact drug effectiveness, safety, and diagnostics. Chiral molecules serve as precise diagnostic tools, aiding in accurate disease detection through unique biomolecule interactions. The article extensively covers chiral drug applications in treating cardiovascular diseases, CNS disorders, local anesthesia, anti-inflammatories, antimicrobials, and anticancer drugs. Additionally, it explores the emerging field of chiral nanomaterials, highlighting their suitability for biomedical applications in diagnostics and therapeutics, enhancing medical treatments.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497268","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":"Induced Chirality in Sulfasalazine by Complexation With Albumins: Theoretical and Experimental Study","authors":"Giulia Saneti Grandini,&nbsp;Valdecir Farias Ximenes,&nbsp;Nelson Henrique Morgon,&nbsp;Aguinaldo Robinson de Souza","doi":"10.1002/chir.23696","DOIUrl":"10.1002/chir.23696","url":null,"abstract":"<p>Through molecular recognition, drugs can interact and complex with macromolecules circulating in the body. The serum albumin transport protein, found in several mammals, has several interaction sites where these molecules can be located. The drug sulfasalazine (SSZ) is known in the literature to complex at drug site 1 (DS1) in human serum (HSA) and bovine serum (BSA) proteins. This complexation can be studied using various spectroscopic techniques. With the techniques used in this work, absorption in the ultraviolet and visible regions (UV–Vis) and electronic circular dichroism (ECD), a significant difference was observed in the results involving HSA and BSA. The application of theoretical methodologies, such as TD-DFT and molecular docking, suggests that the conformation that SSZ assumes in DS1 of the two proteins is different, which exposes it to different amino acid residues and different hydrophobicities. This difference in conformation may be related to the location of DS1 where the drug interacts or to the possibility of SSZ moving in the BSA site, due to its larger size, and moving less freely in HSA.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533747","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":"Self-Assembled Chiral Film Based on Melanin Polymers","authors":"Massimiliano Gaeta,&nbsp;Gabriele Travagliante,&nbsp;Matteo Barcellona,&nbsp;Maria Elena Fragalà,&nbsp;Roberto Purrello,&nbsp;Alessandro D'Urso","doi":"10.1002/chir.23695","DOIUrl":"10.1002/chir.23695","url":null,"abstract":"<div>\u0000 \u0000 <p>Chirality plays a fundamental role in natural phenomena, yet its manifestation on solid surfaces remains relatively unexplored. In this study, we investigate the formation of chiroptical melanin-based self-assembled films on quartz substrates, leveraging mussel-inspired surface chemistry. Water-soluble porphyrins serve as molecular synthons, facilitating the spontaneous formation of hetero-aggregates in phosphate-buffered saline containing L- or D-DOPA. Spectroscopic analysis reveals chiral transfer from DOPA enantiomers to porphyrin hetero-aggregates, followed by the disruption of these latter and subsequent generation of chiral melanin structures in solution. Quartz substrates inserted into these solutions spontaneously accumulate homogeneous melanin-like films over days, demonstrating the feasibility of self-assembly. The resulting films exhibit characteristic UV/Vis and CD spectra, with distinct signals indicating successful chiral induction. Interestingly, the AFM characterizations reveal a distinct surface morphology, and in addition, some thermal and mechanical properties have been taken into account. Overall, this study sheds light on the formation, stability, and chiroptical properties of melanin-based films, paving the way for their application in various fields.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418121","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":"Graph-theoretical chirality measure and chirality–property relations for chemical structures with multiscale mirror asymmetries","authors":"Minjeong Cha,&nbsp;Jessica Ma,&nbsp;Ji-Young Kim,&nbsp;Emine Sumeyra Turali Emre,&nbsp;Nicholas A. Kotov","doi":"10.1002/chir.23678","DOIUrl":"10.1002/chir.23678","url":null,"abstract":"<p>Chirality is an essential geometric property unifying small molecules, biological macromolecules, inorganic nanomaterials, biological microparticles, and many other chemical structures. Numerous chirality measures have attempted to quantify this geometric property of mirror asymmetry and to correlate these measures with physical and chemical properties. However, their utility has been widely limited because these correlations have been largely notional. Furthermore, chirality measures also require prohibitively demanding computations, especially for chiral structures comprised of thousands of atoms. Acknowledging the fundamental problems with quantification of mirror asymmetry, including the ambiguity of sign-variable pseudoscalar chirality measures, we revisit this subject because of the significance of quantifying chirality for quantitative biomimetics and describing the chirality of nanoscale materials that display chirality continuum and scale-dependent mirror asymmetry. We apply the concept of torsion within the framework of differential geometry to the graph theoretical representation of chiral molecules and nanostructures to address some of the fundamental problems and practical limitations of other chirality measures. Chiral gold clusters and other chiral structures are used as models to elaborate a graph-theoretical chirality (GTC) measure, demonstrating its applicability to chiral materials with different degrees of chirality at different scales. For specific cases, we show that GTC provides an adequate description of both the sign and magnitude of mirror asymmetry. The direct correlations with macroscopic properties, such as chiroptical spectra, are enhanced by using the hybrid chirality measures combining parameters from discrete mathematics and physics. Taking molecular helices as an example, we established a direct relation between GTC and optical activity, indicating that this chirality measure can be applied to chiral metamaterials and complex chiral constructs.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/chir.23678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300158","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}

{"title":"Determination of N-centered stereochemistry in N22-methylated chlorophyll-a derivatives and their epimer-dependent optical spectra","authors":"Riko Ataka,&nbsp;Tohru Taniguchi,&nbsp;Kenji Monde,&nbsp;Hitoshi Tamiaki","doi":"10.1002/chir.23681","DOIUrl":"10.1002/chir.23681","url":null,"abstract":"<p>An <i>N</i>-centered epimeric mixture of chlorophyll-<i>a</i> derivatives methylated at the inner nitrogen atom was separated by reverse-phase high-performance liquid chromatography. Circular dichroism (CD) spectroscopic analyses of the epimerically pure N22-methyl-chlorins revealed that the minor first-eluted and major second-eluted stereoisomers were (22<i>S</i>)- and (22<i>R</i>)-configurations, respectively. Their visible absorption and CD spectra in solution were dependent on the N22-stereochemistry. The epimer-dependent spectral changes were independent of the substituents at the peripheral 3-position of the core chlorin chromophore.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/chir.23681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260549","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}

{"title":"Enantioselective liquid–liquid extraction of 2-cyclohexylmandelic acid enantiomers using chiral ionic liquids","authors":"Yachun Luo,&nbsp;Xiaoyu Deng,&nbsp;Yan Zhang,&nbsp;Genlin Sun,&nbsp;Zhihong Yan","doi":"10.1002/chir.23682","DOIUrl":"10.1002/chir.23682","url":null,"abstract":"<p>Obtaining optically pure compounds in an eco-friendly and cost-efficient manner plays an important role in human health and pharmaceutical industry. Racemic separation using multistage stereoselective liquid–liquid extraction has become one of the most practical and effective approach to access homochiral enantiomers. Currently, chiral ionic liquids (CILs) with structural designability have become a promising chiral additive and enable them as adjustable candidates for racemic separation. Herein, a high-effective stereoselective liquid–liquid extraction process composed of imidazolium cations and amino acid-derived anions as the chiral additive was established for racemic 2-cyclohexylmandelic acid (CHMA) separation. We have systematically investigated the choice of organic solvent, concentration of CIL, extraction temperature, and the pH of aqueous phase. For three-stage stereoselective extraction, the maximum enantiomeric excess (<i>e.e</i>.) for CHMA was reached up to 40.6%. Furthermore, the mechanism of steric effect and stereoselective capacity between the CILs and racemic CHMA was discussed and simulated. We envision that the work will facilitate the development of CILs in multistage liquid–liquid extraction and promote the large-scale production of optically pure enantiomers.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160988","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":"Counting the truxillines—11 or more, the question is now","authors":"Tomislav Portada,&nbsp;Zlatko Brkljača","doi":"10.1002/chir.23680","DOIUrl":"10.1002/chir.23680","url":null,"abstract":"<p>Truxillines are a group of tropane alkaloids present in coca leaves that are formed by photochemical dimerization of cinnamoylcocaine(s). Proportion of different truxilline forms present in cocaine serves as its geographical, manufacture, and storage “fingerprint”; thus, the quantitative determination of truxilline content represents one of the powerful methods of analysis and characterization of cocaine samples. Contrary to the statements repeatedly presented in the literature, namely, that there exist exactly 11 truxillines and that every single truxilline is diastereomer of any other, here we show that, in fact, a total of 15 truxillines exist, which can be divided in two structurally isomeric groups—five mutually diastereomeric truxillates and 10 mutually diastereomeric truxinates.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 6","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070413","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}