Absolute Configuration and Predominant Conformations of a Chiral Crown Ether‐Based Colorimetric Sensor: A Vibrational Circular Dichroism Spectroscopy and DFT Study of Chiral Recognition

In the present work, we report a comprehensive vibrational circular dichroism (VCD) spectroscopic study of a chiral crown ether which features an axial chiral 3.3'‐diphenyl‐1,1'‐binaphthyl group as chiral moiety. By comparing the experimental and calculated VCD spectra, we show that the presumably very flexible crown ether preferably adopts only one ring conformation. Conformational flexibility is observed in the 2,4‐dinitrophenyl‐diazophenol group, which was previously introduced for colorimetric detection of primary amines and amino alcohols (Cho et al., Chirality 2011;23:349–353). The VCD spectra of the host–guest complexes with phenyl glycinol (PG) and phenyl alaninol have been studied as well. Based on the spectra calculated, it is shown that the diastereomeric complexes in general can be differentiated using VCD spectroscopy. Furthermore, the experimental VCD spectra of the complexes of the host molecule with PG support the above finding. Chirality 25:294–300, 2013. © 2013 Wiley Periodicals, Inc.     

Chemoenzymatic Approach to Optically Active 4‐Hydroxy‐5‐alkylcyclopent‐2‐en‐1‐one Derivatives: An Application of a Combined Circular Dichroism Spectroscopy and DFT Calculations to Assignment of Absolute Configuration

A series of representative optically active derivatives of 4‐hydroxy‐5‐alkylcyclopent‐2‐en‐1‐one were prepared from the respective 2‐furyl methyl carbinols via the Piancatelli rearrangement followed by the enzymatic kinetic resolution of racemates. Applicability of chiroptical methods (experimental and calculated electronic circular dichroism [ECD] and vibrational circular dichroism [VCD] spectra) to determine the absolute configuration of both stereogenic centers in 4‐hydroxy‐5‐methylcyclopent‐2‐en‐1‐one was demonstrated. It was also demonstrated that the concurrent application of ECD and VCD spectroscopy can be used for the determination of the configuration of two stereogenic centers. Chirality 26:300–306, 2014. © 2014 Wiley Periodicals, Inc.     

Electronic Circular Dichroism of Chiral Alkenes: B3LYP and CAM‐B3LYP Calculations

Time‐dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) are widely used to determine absolute configurations (ACs) of chiral molecules. Two very popular DFT exchange‐correlation functionals, one hybrid (B3LYP) and one long‐range corrected (CAM‐B3LYP), along with a hierarchical sequence of basis sets were investigated, and the ECD spectra predicted for eight alkenes and compared to gas‐phase experimental spectra. Little variation in predicted ECD spectra was found with the basis set size enlargement, but the sensitivity to the functional is greater. Good agreement was obtained only with the CAM‐B3LYP functional, leading to the conclusion that TDDFT calculations of ECD spectra can routinely provide reliable ACs if and only if an appropriate functional is used. For camphene, twistene, syn‐(E)‐bisfenchylidene, and phyllocladene, solvent effects were estimated. Chirality 27:23–31, 2015. © 2014 Wiley Periodicals, Inc.     

Platinum(II) Complexes with 1,10‐Phenanthroline and Hydrophilic Alkoxyacetate Ligands as Potential Antitumor Agents

Four platinum complexes, formulated as [Pt(phen)(OCOCH₂OR)₂] (phen=1,10‐phenanthroline, R=Me, Et, ⁱPr, or ^tBu), have been synthesized and well characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR and ESI‐MS spectroscopy. Replacing chloride groups of the precursor Pt(phen)Cl₂ with alkoxyacetate anions greatly improved the aqueous solubility and cytotoxicity of the resulting platinum complexes. The in vitro cytotoxicity study revealed that complexes 1 – 3 were active in vitro towards four human tumor cell lines, especially complex 1 which exhibited prominent in vitro cytotoxic activity against HCT‐116 cell lines comparable to cisplatin and oxaliplatin. Flow cytometry assay indicated that representative complexes 1 and 2 exerted cytotoxicity on HCT‐116 cell lines through inducing cell apoptosis and blocking cell cycle progression in the S or G2/M phases. The interaction of representative complexes with pET28a plasmid DNA was tested by agarose gel electrophoresis, which demonstrated that complexes 1 and 2 were capable of distorting plasmid DNA mainly by covalent binding and degradation effect.     

Chiral recognition by the copper(II) complex of 6-deoxy-6-N-(2-methylaminopyridine)-β-cyclodextrin

A modified β-cyclodextrin bearing a 2-aminomethylpyridine binding site for copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-β-cyclodextrin, CDampy was synthesized by C₆-monofunctionalization. The acid-base properties of the new ligand in aqueous solution were investigated by potentiometry and calorimetry, and its conformations as a function of pH were studied by NMR and circular dichroism (c.d.). The formation of binary copper(II) complexes was studied by potentiometry, EPR, and c.d. The copper(II) complex was used as chiral selector for the HPLC enantiomeric separation of underivatized aromatic amino acids. Enantioselectivity in the overall stability constants of the ternary complexes with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala enantiomers did not show any difference in stability. These results were consistent with a preferred cis coordination of the amino group of the ligand and of the amino acid in the ternary complexes (“cis effect”), which leads to the inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp-containing ternary complexes, the two enantiomers showed differences in the fluorescence lifetime distribution, consistent with only one conformer of D-Trp and two conformers of L-Trp, and the latter were found to be more accessible to fluorescence quenching by acrylamide and KI. Chirality 9:341–349, 1997. © 1997 Wiley-Liss, Inc.     

Discrimination of Axial and Central Stereogenic Elements in Chiral Bis(oxazolines) Based on Atropisomeric 3,3′‐Bithiophene Scaffolds Through Chiroptical Spectroscopies

Two diastereoisomeric pairs of bis‐oxazolines, provided with a stereogenic center at carbon 4 and based on the 3,3′‐bithiophene atropisomeric scaffold, were synthesized and structurally characterized. They differ in the substituents at positions 2 and 5 of the thiophene rings, which are functionalized with methyl (1) or phenyl (2) groups, respectively. In vibrational circular dichroism (VCD) spectra, recorded in CCl₄ solutions, it is possible to distinctly recognize the characteristic features of axial and central stereogenic elements. In tandem with Density Functional Theory (DFT) calculations, the absolute configuration (AC) of the diastereoisomers was safely established. In this case, VCD was shown to be superior to ECD (electronic circular dichroism) in the assignment of AC. The normal modes, evaluated from DFT calculations, show that the VCD signals in correspondence with the stereogenic axis of the bithiophene unit are different for 1 and 2. The VCD spectra of a molecular analog of 1, the (S)‐2,2′,5,5′‐tetramethyl‐4,4′‐bis‐(diphenylphosphino)‐3,3′‐bithiophene oxide (3), characterized by the same 3,3′‐bithiophene scaffold, but devoid of stereogenic centers, exhibits signals similar to those observed in the case of diastereoisomer (aS,R,R)‐1a, associated with almost identical normal modes. Chirality 28:686–695, 2016. © 2016 Wiley Periodicals, Inc.     

Circular dichroism spectroscopic study of non‐covalent interactions of poly‐L‐glutamic acid with a porphyrin derivative in aqueous solutions

The interactions of poly‐L ‐glutamic acid and a cationic porphyrin derivative in aqueous solutions were studied by the combination of vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopies. It was found that non‐covalent interactions between both agents influence the structure of the polymeric matrix and the guest porphyrins and vice versa, but the physico‐chemical properties of the solutions, especially the pH and the relative permittivity of the solvent, play a key role in the structure of the polypeptide part of the formed complexes. It was shown that the interaction with porphyrins prevents the precipitation of poly‐L ‐glutamic acid in aqueous solution at acidic pH. In special conditions, the porphyrins attached to the polypeptide probably possess face‐to‐face interaction as demonstrated by the enhancement of the characteristic ECD signal and the appearance of sidebands on its short and long wavelength sides. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.     

Chiroptical properties of anionic and neutral nickel(II) bis(dithiolene) complexes based on methyl and dimethyl-dddt ligands

Racemic and enantiopure nickel(II) bis(dithiolene) anionic and neutral complexes based on the methyl-5,6-dihydro-1,4-dithiin-2,3-dithiolate (me-dddt) and dimethyl-5,6-dihydro-1,4-dithiin-2,3-dithiolate (dm-dddt) ligands have been experimentally and theoretically investigated with a special focus on their chiroptical properties. According to the time-dependent density-functional theory (TD-DFT) calculations, the strong near-infrared absorption bands typical for such complexes are only weakly active in circular dichroism (CD), and moreover, they have opposite signs for the axial and equatorial conformations, due to the variation of the angle between the transition electric and magnetic dipole moments, thus leading to the mutual cancellation of their contributions and the absence of these bands in the experimental CD spectra. The influence of the number of stereogenic centers and of the oxidation state of the complexes on their chiroptical properties is highlighted. The solid-state structure of the complex (TMA)[Ni(rac-me-dddt)₂] (TMA = tetramethylammonium), determined by single-crystal X-ray diffraction analysis, shows a rather unusual cis arrangement of the two dithiolene ligands, with the methyl substituents adopting an axial conformation, which is not the most stable one in the gas phase.     

Enantiomeric Separations of Ruthenium (II) Polypyridyl Complexes Using HPLC With Cyclofructan Chiral Stationary Phases

The enantiomeric separation of 21 ruthenium (II) polypyridyl complexes was achieved with a novel class of cyclofructan‐based chiral stationary phases (CSPs) in the polar organic mode. Aromatic derivatives on the chiral selectors proved to be essential for enantioselectivity. The R‐napthylethyl carbamate functionalized cyclofructan 6 (LARIHC CF6‐RN) column proved to be the most effective overall, while the dimethylphenyl carbamate cyclofructan 7 (LARIHC CF7‐DMP) showed complementary selectivity. A combination of acid and base additives was necessary for optimal separations. The retention factor vs. acetonitrile/methanol ratio plot showed a U‐shaped retention curve, indicating that different interactions take place at different polar organic solvent compositions. The separation results indicated that π–π interactions, steric effects, and hydrogen bonding contribute to the enantiomeric separation of ruthenium (II) polypyridyl complexes with cyclofructan chiral stationary phases in the polar organic mode. Chirality 27:64–70, 2015. © 2014 Wiley Periodicals, Inc.     

Enantiomeric 4‐Acylamino‐6‐alkyloxy‐2 Alkylthiopyrimidines As Potential A3 Adenosine Receptor Antagonists: HPLC Chiral Resolution and Absolute Configuration Assignment by a Full Set of Chiroptical Spectroscopy

The chiral separation of enantiomeric couples of three potential A₃ adenosine receptor antagonists: (R/S)‐N‐(6‐(1‐phenylethoxy)‐2‐(propylthio)pyrimidin‐4‐yl)acetamide ( 1 ), (R/S)‐N‐(2‐(1‐phenylethylthio)‐6‐propoxypyrimidin‐4‐yl)acetamide ( 2 ), and (R/S)‐N‐(2‐(benzylthio)‐6‐sec‐butoxypyrimidin‐4‐yl)acetamide ( 3 ) was achieved by high‐performance liquid chromatography (HPLC). Three types of chiroptical spectroscopies, namely, optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD), were applied to enantiomeric compounds. Through comparison with Density Functional Theory (DFT) calculations, encompassing extensive conformational analysis, full assignment of the absolute configuration (AC) for the three sets of compounds was obtained. Chirality 28:434–440, 2016. © 2016 Wiley Periodicals, Inc.     

A Solid Phase Vibrational Circular Dichroism Study of Polypeptide–Surfactant Interaction

We studied the interaction of poly‐l ‐lysine (PLL) and poly‐l ‐arginine (PLAG) with sodium dodecyl sulfate (SDS) surfactant and the interaction of poly‐l‐ glutamic acid (PLGA) and poly‐l ‐aspartic acid (PLAA) with tetradecyltrimethylammonium bromide (TTAB) surfactant using vibrational circular dichroism (VCD) spectroscopy in the region of C‐H stretching vibration and in the Amide I region both in solution and in mulls. A chirality transfer from polypeptides to achiral surfactants was observed in the C‐H stretching region, where measurements in solution were impossible. This observation was enabled by a special sample treatment technique using lyophilization and the preparation of mulls. This technique demonstrated itself as an interesting and beneficial tool for VCD measurements. In addition, we observed that SDS changed the secondary structure of PLL to the β‐sheet and of PLAG to the α‐helix. TTAB disrupted the PLGA and PLAA structure. These results were obtained in the mull but were confirmed by the VCD spectra measured in solution and by electronic circular dichroism. The chirality transfer from the polypeptides to SDS was caused by polypeptides ordered into a specific conformation during the interaction, while in the TTBA system it was induced primarily by the chirality of the amino acid residues. Chirality 27:965–972, 2015. © 2015 Wiley Periodicals, Inc.     

Fabrication of Water‐Repellent Platinum(II) Complex‐Based Photon Downshifting Layers for Perovskite Solar Cells by Ultrasonic Spray Deposition

Despite a rapid increase in light harvesting efficiencies, organic–inorganic hybrid perovskite solar cells (PSCs) exhibit relatively inefficient photocurrent generation in the UV region and severe degradation when exposed to UV light and humidity. Herein, to enhance UV and humidity stability as well as photocurrent generating efficiency, a water‐repellent platinum(II) complex, Pt‐F , is developed as a luminescent photon downshifting layer (PDL) for PSCs. The Pt‐F PDL is fabricated on the glass substrate of a PSC using ultrasonic spray deposition, resulting in a considerably higher crystallinity and photoluminescence quantum yield (PLQY) than those fabricated by conventional spin‐coating processes (PLQYs of 77% and 19%, respectively). A maximum device performance of 22.0% is achieved through the addition of a PDL coating to a 21.4% efficient PSC owing to the long‐range photon downshifting effect of Pt‐F , as confirmed by the enhanced spectral response of the device in the UV region. Moreover, remarkable improvements in UV and humidity stability are observed in Pt‐F ‐coated PSCs. The versatile effects of the Pt‐F ‐based PDL, when fabricated by ultrasonic spray deposition, suggest wide ranging applicability that can improve the performance and stability of other optoelectronic devices.     

ROS-Mediated Antitumor Activity,Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2-(Diphenylphosphino)pyridine Ligands

Platinum-based drugs have been widely used in cancer treatment. However, their severe side effects have limited their use. So, researchers have been striving to find compounds with fewer side effects and greater efficacy, to overcome these drawbacks. Here, the cytotoxicity of platinum(II) complexes containing 2-(diphenylphosphino)pyridine ligands have been studied on human lung (A549), ovarian (SKOV3), breast (MCF-7) cancer, and normal breast (MCF-10A) cell lines. The most potent compound exhibits a marked cell growth-inhibitory effect against ovarian and lung cancer cells with IC₅₀ values of 9.41 and 5.58 μM, respectively, which were significantly better than that observed for cisplatin (19.02, and 8.64 μM). Additionally, all complexes achieved significantly lower cytotoxicity towards MCF-10A. To investigate the interaction of complexes with DNA, an electrophoresis mobility shift assay was conducted, which indicated that complexes bind to DNA and affect its electrophoretic mobility. An analysis of apoptosis in A549 cells supported the conclusion that they inhibits cell proliferation via induction of apoptosis in a concentration-dependent manner. Molecular docking was also used to investigate the interactions of compounds with different DNA structures. These compounds have the ability to be a suitable pharmaceutical compound with further investigations in the field of cancer research.     

Vibrational Circular Dichroism (VCD), VCD Exciton Coupling,and X‐ray Determination of the Absolute Configuration of an α,β‐Unsaturated Germacranolide

The absolute configuration of 1 was deduced by vibrational circular dichroism together with the evaluation of the Flack and Hooft X‐ray parameters. Vibrational circular dichroism exciton coupling, using the carbonyl group signals, confirmed the absolute configuration of 2 . In addition, sodium borohydride reduction of the 11,13‐double bond of 6‐epi‐desacetyllaurenobiolide ( 1 ) yields an almost equimolecular mixture of C11 epimers, while reduction of the same double bond of 6‐epi‐laurenobiolide ( 2 ) provided almost exclusively the (11S) diastereoisomer 4 . Chirality 27:247–252, 2015. © 2015 Wiley Periodicals, Inc.     

Chiral Amine Enantiomeric Excess Determination Using Self‐Assembled Octahedral Fe(II)‐Imine Complexes

A receptor assembly composed of iron(II) triflate and pyridine‐2,6‐dicarbaldehyde was used to determine the enantiomeric excess (ee) of alpha‐chiral primary amines using circular dichroism spectroscopy. The alpha chiral amines condense with the dialdehyde to form a diimine, which forms a 2:1 octahedral complex with iron(II). The ee values of unknown concentrations of alpha‐chiral amines were determined by constructing calibration curves for each amine and then measuring the ellipticity at 600 nm. This improves our previously reported assay for ee determination of chiral primary amines by further increasing the wavelength at which CD is measured and reducing the absolute error of the assay. Chirality 27:294–298, 2015. 2015 Wiley Periodicals, Inc.     

Synthesis,Structural Characterization,and Chiroptical Studies of Bidentate Salen‐Type Lanthanide (III) Complexes

The salen‐type ligand prepared with (R,R) diphenylethan‐1,2‐diamine and salicylaldehyde provides stable and inert complexes KLnL₂ upon simple reaction with lanthanide halides or pseudohalides LnX₃ (Ln = Tb³⁺‐Lu³⁺; X = Cl^? or TfO^?) of its potassium salt. All the complexes were completely characterized through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in the UV and some (Er³⁺, Tm³⁺, Yb³⁺) also with Near‐IR ECD (NIR‐ECD) and luminescence (Tb³⁺, Tm³⁺). Careful analysis of the NMR shifts demonstrated that the complexes are isostructural in solution and afforded an accurate geometry. This was further confirmed by means of Density Functional Theory (DFT) optimization of the Lu³⁺ complex, and by comparing the ligand‐centered experimental and time‐dependent TD‐DFT computed UV‐ECD spectra. As final validation, we used the NIR‐ECD spectrum of the Yb³⁺ derivative calculated by means of Richardson's equations. The excellent match between calculated and experimental ECD spectra confirm the quality of the NMR structure.  Chirality 27:857–863, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis and X‐ray diffraction study of a chiral bis‐phosphahelicene palladium (II) complex

As a complement to our previous studies on the development of a class of chiral phosphahelicenes, this article discloses the synthesis, spectroscopic, and structural characterizations of a new phosphahelicene transition metal complex. It demonstrates the ability of these hindered chiral ligands to coordinate Pd (II) in trans‐complexes Cl₂Pd(L*)₂. In the solid state, the complex adopts a C2‐symmetric arrangement with two ligands facing each other on the same face of the coordination plane. X‐Ray data highlight bending of the Pd (II) unit from the expected planar coordination geometry that might be due to a significant π‐π stacking effect between the central rings of two helical units.     

Tetramethyl‐Bis(ethylenedithio)‐Tetrathiafulvalene (TM‐BEDT‐TTF) Revisited: Crystal Structures,Chiroptical Properties,Theoretical Calculations,and a Complete Series of Conducting Radical Cation Salts

The (S,S,S,S) and (R,R,R,R) enantiomers of tetramethyl‐bis(ethylenedithio)‐tetrathiafulvalene (TM‐BEDT‐TTF) show equatorial conformation for the four methyl groups in the solid state, according to the single‐crystal X‐ray analyses. Theoretical calculations at the Density Functional Theory (DFT) and time‐dependent (TD) DFT levels indicate higher gas phase stability for the axial conformer than the equatorial one by 1.25 kcal · mole^‐1 and allow the assignment of the UV–vis and circular dichroism transitions. A complete series of radical cation salts of 1:1 stoichiometry with the triiodide anion I₃^‐ was obtained by electrocrystallization of both enantiopure and racemic forms of the donor. In the packing the donors are organized in dimers that further interact through S · · · S intermolecular contacts and the triiodide anions lie parallel to pairs of oxidized donors. The conductivity of the racemate, which adopts the same, but disordered, structural type, is considerably lower, with much higher activation energy. Chirality 25:466–474, 2013.© 2013 Wiley Periodicals, Inc.     

Electronic Circular Dichroism of [16]Helicene With Simplified TD‐DFT: Beyond the Single Structure Approach

The electronic circular dichroism (ECD) spectrum of the recently synthesized [16]helicene and a derivative comprising two triisopropylsilyloxy protection groups was computed by means of the very efficient simplified time‐dependent density functional theory (sTD‐DFT) approach. Different from many previous ECD studies of helicenes, nonequilibrium structure effects were accounted for by computing ECD spectra on "snapshots" obtained from a molecular dynamics (MD) simulation including solvent molecules. The trajectories are based on a molecule specific classical potential as obtained from the recently developed quantum chemically derived force field (QMDFF) scheme. The reduced computational cost in the MD simulation due to the use of the QMDFF (compared to ab‐initio MD) as well as the sTD‐DFT approach make realistic spectral simulations feasible for these compounds that comprise more than 100 atoms. While the ECD spectra of [16]helicene and its derivative computed vertically on the respective gas phase, equilibrium geometries show noticeable differences, these are “washed” out when nonequilibrium structures are taken into account. The computed spectra with two recommended density functionals (ωB97X and BHLYP) and extended basis sets compare very well with the experimental one. In addition we provide an estimate for the missing absolute intensities of the latter. The approach presented here could also be used in future studies to capture nonequilibrium effects, but also to systematically average ECD spectra over different conformations in more flexible molecules. Chirality 28:365–369, 2016. © 2016 Wiley Periodicals, Inc.