Photografted methacrylate-based monolithic columns coated with cellulose tris(3,5-dimethylphenylcarbamate) for chiral separation in CEC

A chiral capillary monolithic column for enantiomer separation in capillary electrochromatography was prepared by coating cellulose tris(3,5-dimethylphenylcarbamate) on porous glycidyl methacrylate-co-ethylene dimethacrylate monolith in capillary format grafted with chains of [2(methacryloyloxy)ethyl] trimethylammonium chloride. The surface modification of the monolith by the photografting of [2(methacryloyloxy)ethyl] trimethylammonium chloride monomer as well as the coating conditions of cellulose tris(3,5-dimethylphenylcarbamate) onto the grafted monolithic scaffold were optimized to obtain a stable and reproducible chiral stationary phase for capillary electrochromatography. The effect of organic modifier (acetonitrile) in aqueous mobile phase for the enantiomer separation by capillary electrochromatography was also investigated. Several pairs of enantiomers including acidic, neutral, and basic analytes were tested and most of them were partially or completely resolved under aqueous mobile phases. The prepared monolithic chiral stationary phases exhibited a good stability, repeatability, and column-to-column reproducibility, with relative standard deviations below 11% in the studied electrochromatographic parameters.Fil: Echevarria, Romina Noel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Carrasco Correa, Enrique Javier. Universidad de Valencia; EspañaFil: Keunchkarian, Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Reta, Mario Roberto. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Herrero Martinez, José Manuel. Universidad de Valencia; Españ

Chiral Nanoceramics

The study of different chiral inorganic nanomaterials has been experiencing rapid growth during the past decade, with its primary focus on metals and semiconductors. Ceramic materials can substantially expand the range of mechanical, optical, chemical, electrical, magnetic, and biological properties of chiral nanostructures, further stimulating theoretical, synthetic, and applied research in this area. An ever‐expanding toolbox of nanoscale engineering and self‐organization provides a chirality‐based methodology for engineering of hierarchically organized ceramic materials. However, fundamental discoveries and technological translations of chiral nanoceramics have received substantially smaller attention than counterparts from metals and semiconductors. Findings in this research area are scattered over a variety of sources and subfields. Here, the diversity of chemistries, geometries, and properties found in chiral ceramic nanostructures are summarized. They represent a compelling materials platform for realization of chirality transfer through multiple scales that can result in new forms of ceramic materials. Multiscale chiral geometries and the structural versatility of nanoceramics are complemented by their high chiroptical activity, enantioselectivity, catalytic activity, and biocompatibility. Future development in this field is likely to encompass chiral synthesis, biomedical applications, and optical/electronic devices. The implementation of computationally designed chiral nanoceramics for biomimetic catalysts and quantum information devices may also be expected.Chiral nanoceramics are emerging as a remarkably active area of chiral research. It is still in its infant stage and is thus full of challenges and opportunities. Recent advances in the diversity of chemistries, geometries, and properties of chiral ceramic nanostructures are reviewed. An outlook of synthesis, computational methods, and emerging applications of chiral nanoceramics is presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163453/2/adma201906738_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163453/1/adma201906738.pd

Comparative enantioseparation of planar chiral ferrocenes on polysaccharide-based chiral stationary phases.

Planar chiral ferrocenes are well-known compounds that have attracted interest for application in synthesis, catalysis, material science, and medicinal chemistry for several decades. In spite of the fact that asymmetric synthesis procedures for obtaining enantiomerically enriched ferrocenes are available, sometimes, the accessible enantiomeric excess of the chiral products is unsatisfactory. In such cases and for resolution of racemic planar chiral ferrocenes, enantioselective high-performance liquid chromatography (HPLC) on polysaccharide-based chiral stationary phases (CSPs) has been used in quite a few literature articles. However, although moderate/high enantioselectivities have been obtained for planar chiral ferrocenes bearing polar substituents, the enantioseparation of derivatives containing halogens, or exclusively alkyl groups, remains rather challenging. In this study, the enantioseparation of ten planar chiral 1,2- and 1,3-disubstituted ferrocenes was explored by using five polysaccharide-based CSPs under multimodal elution conditions. Baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.20 to 2.92. The presence of π-extended systems in the analyte structure was shown to impact affinity of the most retained enantiomer toward amylose-based selectors, observing retention times higher than 80 min with methanol-containing mobile phases (MPs). Electrostatic potential (V) analysis and molecular dynamics (MD) simulations were used in order to study interaction modes at the molecular level

(S)-(+)-Ketamine hydro­chloride

The crystal structure of the title compound {systematic name: (S)-(+)-N-[1-(2-chloro­phen­yl)-2-oxocyclo­hexyl]meth­anam­in­ium chloride}, C13H17ClNO+·Cl−, was determined at 90 (2) K. The (S)-(+)-ketamine hydro­chloride salt is a well known anesthetic compound and is dramatically more potent than its R isomer. In the title compound, the cyclo­hexa­none ring adopts a chair conformation with the oxo group in the equatorial orientation. The methyl­amino and 2-chloro­phenyl groups at the 2-position have an equatorial and an axial orientation, respectively. The packing of ions is stabilized by an infinite one-dimensional ⋯Cl⋯H—N—H⋯Cl⋯ hydrogen-bonding network, involving NH2 + groups as donors and chloride anions as acceptors

Exploring interaction modes between polysaccharide-based selectors and biologically active 4,4′-bipyridines by experimental and computational analysis

In the last few years, chiral 4,4′-bipyridine derivatives have been developed for different applications in catalysis, enantioseparation science, supramolecular and theoretical chemistry by modulating the activity of the molecular system through the introduction of specific substituents in the heteroaromatic scaffold. More recently, the biological activity of 2′-substituted-3,3′,5,5′-tetrachloro-2-iodo-4,4′-bipyridines has been explored in the field of transthyretin (TTR) fibrillogenesis inhibition, and the anticancer cytotoxicity of some derivatives is currently under systematic investigation. In this frame, the high-performance liquid chromatography (HPLC) enantioseparation of four atropisomeric 2,2′-disubstituted-4,4′-bipyridines (R, R’ = Ar, I), which contain multiple interaction sites, such as hydrogen bonding (HB) donors and acceptors, halogen bond (XB) donors, and -extended electronic clouds, was explored by using n-hexane (Hex)/2-propanol (2-PrOH) 90:10 v/v as a mobile phase (MP), and eight chiral columns with coated and immobilized amylose- and cellulose-based relectors. The impact of subtle structural variations of analytes and selectors on their mutual intermolecular interactivity was evaluated in terms of retention (k) and selectivity () factors. On this basis, chromatographic analysis based on systematic screening of analytes and selectors was integrated with electrostatic potential (V) analysis and molecular dynamics (MD) simulations as computational techniques. The effect of temperature on retention, selectivity, and enantiomer elution order (EEO) of the analytes with coated and immobilized amylose tris(3,5-dimethylphenylcarbamate) was also considered by comparing the variation of the thermodynamic profile associated with each enantioseparation. Chromatographic responses proved to be strictly dependent on specific regions within the analyte, and functions of different interactions sites of the analytes as the structure of the chiral selector changes were significantly disclosed

Enantioseparation of 5,5'-Dibromo-2,2'-Dichloro-3-Selanyl-4,4'-Bipyridines on Polysaccharide-Based Chiral Stationary Phases: Exploring Chalcogen Bonds in Liquid-Phase Chromatography

he chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive electrostatic potential (V) with nucleophilic partners such as lone pairs, π-clouds, and anions (acceptors). In the last few years, promising applications of ChBs in catalysis, crystal engineering, molecular biology, and supramolecular chemistry have been reported. Recently, we explored the high-performance liquid chromatography (HPLC) enantioseparation of fluorinated 3-arylthio-4,4-bipyridines containing sulfur atoms as ChB donors. Following this study, herein we describe the comparative enantiosepa-ration of three 5,5-dibromo-2,2-dichloro-3-selanyl-4,4-bipyridines on polysaccharide-based chiral stationary phases (CSPs) aiming to understand function and potentialities of selenium σ-holes in the enantiodiscrimination process. The impact of the chalcogen substituent on enantioseparation was explored by using sulfur and non-chalcogen derivatives as reference substances for comparison. Our investigation also focused on the function of the perfluorinated aromatic ring as a π-hole donor recognition site. Thermodynamic quantities associated with the enantioseparation were derived from van't Hoff plots and local electron charge density of specific molecular regions of the interacting partners were inspected in terms of calculated V. On this basis, by correlating theoretical data and experimental results, the participation of ChBs and π-hole bonds in the enantiodiscrimination process was reasonably confirmed

Retarded photooxidation of cyamemazine in biomimetic microenvironments

Cyamemazine (CMZ) is a neuroleptic drug that mediates cutaneous phototoxicity in humans. Here, the photobehavior of CMZ has been examined within (1)-acid glycoproteins, - and -cyclodextrins and SDS micelles. In all these microenvironments, CMZ emission was enhanced and blue-shifted, and its lifetime was longer. Irradiation of the entrapped drug at 355nm, under air; led to the N,S-dioxide. Within glycoproteins or SDS micelles the reaction was clearly slower than in phosphate buffered solution (PBS); protection by cyclodextrins was less marked. Transient absorption spectroscopy in PBS revealed formation of the triplet state ((3)CMZ*) and the radical cation (CMZ(+center dot)). Upon addition of glycoprotein, the contribution of CMZ(+center dot) became negligible, whereas (3)CMZ* dominated the spectra; in addition, the triplet lifetime became considerably longer. In cyclodextrins, this occurred to a lower extent. In all microheterogeneous systems, quenching by oxygen was slower than in solution; this was most remarkable inside glycoproteins. The highest protection from photooxidation was achieved inside SDS micelles. The results are consistent with photooxidation of CMZ through photoionization and subsequent trapping of the resulting radical cation by oxygen. This reaction is extremely sensitive to the medium and constitutes an appropriate probe for localization of the drug within a variety of biological compartments.Financial support from the Spanish Government (CTQ2010-14882, BES-2011-043706, JCI-2010-06204) and from the Generalitat Valenciana (PROMETEOII/2013/005) is gratefully acknowledged.Limones Herrero, D.; Pérez Ruiz, R.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2014). Retarded photooxidation of cyamemazine in biomimetic microenvironments. Photochemistry and Photobiology. 90(5):1012-1016. https://doi.org/10.1111/php.12303S10121016905Feinberg, A. P., & Snyder, S. H. (1975). Phenothiazine drugs: structure-activity relationships explained by a conformation that mimics dopamine. Proceedings of the National Academy of Sciences, 72(5), 1899-1903. doi:10.1073/pnas.72.5.1899Jaszczyszyn, A., Gąsiorowski, K., Świątek, P., Malinka, W., Cieślik-Boczula, K., Petrus, J., & Czarnik-Matusewicz, B. (2012). Chemical structure of phenothiazines and their biological activity. Pharmacological Reports, 64(1), 16-23. doi:10.1016/s1734-1140(12)70726-0Domínguez, J. N., López, S., Charris, J., Iarruso, L., Lobo, G., Semenov, A., … Rosenthal, P. J. (1997). Synthesis and Antimalarial Effects of Phenothiazine Inhibitors of aPlasmodium falciparumCysteine Protease. Journal of Medicinal Chemistry, 40(17), 2726-2732. doi:10.1021/jm970266pAaron, J. J., Gaye Seye, M. D., Trajkovska, S., & Motohashi, N. (2008). Bioactive Phenothiazines and Benzo[a]phenothiazines: Spectroscopic Studies, and Biological and Biomedical Properties and Applications. Bioactive Heterocycles VII, 153-231. doi:10.1007/7081_2008_125White, N. D., & Lenz, T. L. (2013). Drug-Induced Photosensitivity and the Major Culprits. American Journal of Lifestyle Medicine, 7(3), 189-191. doi:10.1177/1559827613475575Onoue, S., Kato, M., Inoue, R., Seto, Y., & Yamada, S. (2013). Photosafety Screening of Phenothiazine Derivatives With Combined Use of Photochemical and Cassette-Dosing Pharmacokinetic Data. Toxicological Sciences, 137(2), 469-477. doi:10.1093/toxsci/kft260Albini , A. E. Fasani B. D. Glass M. E. Brown P. M. Drummond 1998 Photoreactivity versus activity of a selected class of phenothiazines: A comparative study Drugs, Photochemistry and Photostability A. Albini and E. Fasani 134 149 Royal Society of Chemistry CambridgeElisei, F., Latterini, L., Gaetano Aloisi, G., Mazzucato, U., Viola, G., Miolo, G., … Dall’Acqua, F. (2002). Excited-state Properties and In Vitro Phototoxicity Studies of Three Phenothiazine Derivatives¶. Photochemistry and Photobiology, 75(1), 11. doi:10.1562/0031-8655(2002)0752.0.co;2García, C., Piñero, L., Oyola, R., & Arce, R. (2009). Photodegradation of 2-chloro Substituted Phenothiazines in Alcohols. Photochemistry and Photobiology, 85(1), 160-170. doi:10.1111/j.1751-1097.2008.00412.xRonzani, F., Trivella, A., Arzoumanian, E., Blanc, S., Sarakha, M., Richard, C., … Lacombe, S. (2013). Comparison of the photophysical properties of three phenothiazine derivatives: transient detection and singlet oxygen production. Photochemical & Photobiological Sciences, 12(12), 2160. doi:10.1039/c3pp50246eFournier, T., Medjoubi-N, N., & Porquet, D. (2000). Alpha-1-acid glycoprotein. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1482(1-2), 157-171. doi:10.1016/s0167-4838(00)00153-9Safaa, E.-G., Wollert, U., & Müller, W. E. (1983). Binding of Several Phenothiazine Neuroleptics to a Common Binding Site of α1-Acid Glycoprotein, Orosomucoid. Journal of Pharmaceutical Sciences, 72(2), 202-205. doi:10.1002/jps.2600720229MIYOSHI, T., SUKIMOTO, K., & OTAGIRI, M. (1992). Investigation of the Interaction Mode of Phenothiazine Neuroleptics with α1-Acid Glycoprotein. Journal of Pharmacy and Pharmacology, 44(1), 28-33. doi:10.1111/j.2042-7158.1992.tb14358.xTaheri, S., Cogswell, L. P., Gent, A., & Strichartz, G. R. (2003). Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α1-Acid Glycoprotein. Journal of Pharmacology and Experimental Therapeutics, 304(1), 71-80. doi:10.1124/jpet.102.042028Schill, G., Wainer, I. W., & Barkan, S. A. (1986). Chiral separations of cationic and anionic drugs on an α1-acid glycoprotein-bonded stationary phase (enantiopac®). Journal of Chromatography A, 365, 73-88. doi:10.1016/s0021-9673(01)81544-2Michishita, T., Franco, P., & Zhang, T. (2010). New approaches of LC-MS compatible method development on α1-acid glycoprotein-based stationary phase for resolution of enantiomers by HPLC. Journal of Separation Science, 33(23-24), 3627-3637. doi:10.1002/jssc.201000627Hermansson, J., & Grahn, A. (1995). Optimization of the separation of enantiomers of basic drugs retention mechanisms and dynamic modification of the chiral bonding properties on a α1-acid glycoprotein column. Journal of Chromatography A, 694(1), 57-69. doi:10.1016/0021-9673(94)00936-4Caetano, W., & Tabak, M. (2000). Interaction of Chlorpromazine and Trifluoperazine with Anionic Sodium Dodecyl Sulfate (SDS) Micelles: Electronic Absorption and Fluorescence Studies. Journal of Colloid and Interface Science, 225(1), 69-81. doi:10.1006/jcis.2000.6720Ghosh, H. N., Sapre, A. V., Palit, D. K., & Mittal, J. P. (1997). Picosecond Flash Photolysis Studies on Phenothiazine in Organic and Micellar Solution. The Journal of Physical Chemistry B, 101(13), 2315-2320. doi:10.1021/jp963028zIRIE, T., SUNADA, M., OTAGIRI, M., & UEKAMA, K. (1983). Protective mechanism of .BETA.-cyclodextrin for the hemolysis induced with phenothiazine neuroleptics in vitro. Journal of Pharmacobio-Dynamics, 6(6), 408-414. doi:10.1248/bpb1978.6.408Chankvetadze, B., Kartozia, I., Burjanadze, N., Bergenthal, D., Luftmann, H., & Blaschke, G. (2001). Enantioseperation of chiral phenothiazine derivatives in capillary electrophoresis using cyclodextrin type chiral selectors. Chromatographia, 53(S1), S290-S295. doi:10.1007/bf02490344Conilleau, V., Dompmartin, A., Michel, M., Verneuil, L., & Leroy, D. (2000). Photoscratch testing in systemic drug-induced photosensitivity. Photodermatology, Photoimmunology and Photomedicine, 16(2), 62-66. doi:10.1034/j.1600-0781.2000.d01-5.xMorlière, P., Bosca, F., Miranda, M. A., Castell, J. V., & Santus, R. (2004). 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Quenched phosphorescence as alternative detection mode in the chiral separation of methotrexate by electrokinetic chromatography

Quenched phosphorescence was used, for the first time, as detection mode in the chiral separation of methotrexate (MTX) enantiomers by electrokinetic chromatography. The detection is based on dynamic quenching of the strong emission of the phosphorophore 1-bromo-4-naphthalene sulfonic acid (BrNS) by MTX under deoxygenated conditions. The use of a background electrolyte with 3 mg/mL 2-hydroxypropyl-β-cyclodextrin and 20% MeOH in 25 mM phosphate buffer (pH 7.0) and an applied voltage of 30 kV allowed the separation of l-MTX and its enantiomeric impurity d-MTX with sufficient resolution. In the presence of 1 mM BrNS, a detection limit of 3.2 × 10−7 M was achieved, about an order of magnitude better than published techniques based on UV absorption. The potential of the method was demonstrated with a degradation study and an enantiomeric purity assessment of l-MTX. Furthermore, l-MTX was determined in a cell culture extract as a proof-of-principle experiment to show the applicability of the method to biological samples