Enantioselective cytotoxicity of ZnS:Mn quantum dots in A549 cells

Chirality strongly influences many biological properties of materials, such as cell accumulation, enzymatic activity, and toxicity. In the past decade, it has been shown that quantum dots (QDs), fluorescent semiconductor nanoparticles with unique optical properties, can demonstrate optical activity due to chiral ligands bound on their surface. Optically active QDs could find potential applications in biomedical research, therapy, and diagnostics. Consequently, it is very important to investigate the interaction of QDs capped with chiral ligands with living cells. The aim of our study was to investigate the influence of the induced chirality of Mn‐doped ZnS QDs on the viability of A549 cells. These QDs were stabilized with D‐ and L‐cysteine using a ligand exchange technique. The optical properties of QDs were studied using UV–Vis, photoluminescence (PL), and circular dichroism (CD) spectroscopy. The cytotoxicity of QDs was investigated by high content screening analysis. It was found that QDs stabilized by opposite ligand enantiomers, had identical PL and UV–Vis spectra and mirror‐imaged CD spectra, but displayed different cytotoxicity: QDs capped with D‐cysteine had greater cytotoxicity than L‐cysteine capped QDs.     

Stereochemical Properties of Multidentate Nitrogen Donor Ligands and Their Copper Complexes by Electronic CD and DFT

UV–Vis and electronic circular dichroism (ECD) spectroscopy, complemented with Density Functional Theory (DFT) calculations, were used to elucidate the structural diversities of three multidentate nitrogen donor ligands and two associated copper complexes in solution directly. The three chiral salen ligands all consist of trans‐cyclohexane‐1,2‐diamine as a chiral scaffold and also of pyridine rings as chromophores, differing only in the linking groups between the two functional groups mentioned above. Very different ECD intensities and somewhat different ECD patterns were observed for these ligands and satisfactorily interpreted theoretically. For the geometry optimization and spectral simulation of the open‐shell metal complexes, the LANL2DZ basis set with effective core potential for the Cu and Cl atoms and pure cc‐pVTZ for the rest of the atoms was utilized. The performance of the same calculations with the polarization functions (f,g) from the cc‐pVTZ basis added to the LANL2DZ basis was compared. While the three ligands exhibit different conformational flexibility, the associated copper complexes show great rigidity imposed by the metal–ligand coordination, taking on a single structure in each case. In addition, dispersion interactions were shown to change the conformational stability ordering of the ligands noticeably and to exert considerable influence on the simulated UV–Vis and ECD spectra. Chirality 28:545–555, 2016. © 2016 Wiley Periodicals, Inc.     

Heparin-induced circular dichroism of an achiral, bicyclic species

Antimalarial drugs have shown potential in suppressing the role of glycosaminoglycans (GAGs) in the pathology of prion protein conformational disorders (e.g. "Mad Cow" disease) by competing for sites of electrostatic interaction. In this study, circular dichroism (CD) and UV/Visible (UV/Vis) absorption spectroscopy techniques were used to investigate the interactions between N-methyl-N'-(7-chloro-4-quinolyl)-1,3-diaminopropane (QD), an achiral, bicyclic compound similar to previously investigated antimalarial drugs, and heparin, a complex GAG that is frequently used as a clinical anticoagulant. Relatively intense heparin-induced CD features were observed for QD and were noted to be radically different from previous studies using related chiral drugs, underscoring the importance of the Pfieffer effect on this and similar heparin research. Additionally, the induced CD for QD was observed to be highly dependent upon drug concentration, heparin concentration, system pH, equilibration time, and ionic strength. These results, in connection with recent work, provide new insight into the nature of the association between GAGs and antimalarial species.     

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.     

Color and chirality: carotenoid self-assemblies in flower petals

As a novel phenomenon, optical activity--often very strong--has been detected by circular dichroism (CD) spectroscopy in carotenoid-containing living flowers of several species belonging to different families. Using natural pure xanthophyll esters, very similar CD spectra were obtained in vitro, proving the ability of these molecules to form chiral self-assemblies. The relationship between the ultrastructure of the chromoplast, its chemical composition and the optical activity is discussed. The applicability of CD spectroscopy for studying intact plant tissue is emphasized.     

Binding of netropsin to DNA in complexes with polypeptides containing repetitive lysine sequences

The interaction of the antibiotic netropsin with calf thymus DNA, T4 DNA and poly(dA-dT) . poly(dA-dT) in complexes with sequential polypeptides containing repetitive lysine sequences and histone H1 was investigated using circular dichroism spectroscopy and equilibrium dialysis. Both soluble DNA-polypeptide complexes and insoluble complexes showed binding of netropsin. The possibility of displacement of polypeptides from DNA binding sites by competition with netropsin molecules was eliminated by experiments using 14C-labelled polypeptides. From the analysis of CD titration behavior as well as from the results of equilibrium dialysis studies it follows that netropsin does not compete with polypeptides for DNA binding sites, which suggests that these two ligands occupy different sites. Various explanations for minor differences in the CD behavior of the bound netropsin in the saturation region are also discussed.     

Zn2+ selectively stabilizes FdU-substituted DNA through a unique major groove binding motif

We report, based on semi-empirical calculations, that Zn(2+) binds duplex DNA containing consecutive FdU-dA base pairs in the major groove with distorted trigonal bipyramidal geometry. In this previously uncharacterized binding motif, O4 and F5 on consecutive FdU are axial ligands while three water molecules complete the coordination sphere. NMR spectroscopy confirmed Zn(2+) complexation occurred with maintenance of base pairing while a slight hypsochromic shift in circular dichroism (CD) spectra indicated moderate structural distortion relative to B-form DNA. Zn(2+) complexation inhibited ethidium bromide (EtBr) intercalation and stabilized FdU-substituted duplex DNA (ΔT(m) > 15 °C). Mg(2+) neither inhibited EtBr complexation nor had as strong of a stabilizing effect. DNA sequences that did not contain consecutive FdU were not stabilized by Zn(2+). A lipofectamine preparation of the Zn(2+)-DNA complex displayed enhanced cytotoxicity toward prostate cancer cells relative to the individual components prepared as lipofectamine complexes indicating the potential utility of Zn(2+)-DNA complexes for cancer treatment.     

Methods for determining the absolute configurations of marine ladder-shaped polyethers

Marine dinoflagellates produce a unique family of bioactive substances featuring multiple ether rings aligned in a ladder shape. These are large, complex molecules with potent bioactivity. Targeted chiral centers sit on either the skeletal ladders or on the side chains of these compounds. However, the laborious steps of isolation and purification severely diminish the amount of sample available for assigning these chiral centers via structural investigations. Three important methods were used to assign the stereochemistry of the molecules, (a) circular dichroism (CD) spectroscopy, (b) labeling with fluorescent chiral reagents for high-performance liquid chromatography (HPLC) analysis, and (c) derivatization with anisotropic reagents for nuclear magnetic resonance (NMR) analysis. The addition of fluorescent chiral reagents allowed for the use of much less material than typically required. In this review, we present examples of the determination of absolute configurations in ladder-shaped polyethers. The targeted compounds include ciguatoxins (CTXs), gymnocin-B, gambieric acids, prymnesin-2, maitotoxin, yessotoxins, gambierol, brevisamide, and brevisin.     

Helical screw sense bias in chiral polyfluorene stimulated by solvent

Conjugated homopolymer poly(9,9‐bis(3‐((S )‐2‐methylbutylpropanoate))fluorene) (PSF) with chiral pendants was synthesized and characterized. Dissolution experiments show that PSF is well dissolved in racemic limonene at high temperature and begins aggregating upon sequential cooling treatment. The corresponding assemblies were transferred to quartz plate by the spin‐coating method. Comparably, film casting from chloroform solution was also prepared. Upon annealing thermal treatments, these PSF films exhibited perfect mirror circular dichroism (CD) Cotton effects and dissymmetry ratios. Optical absorption spectroscopy (UV‐vis), CD, and fluorescence spectroscopy results reveal that chiral side chains successfully induced M ‐ and P ‐helical structures in aggregates and films, and this significant difference was ascribed to their differential supramolecular conformations.     

Comparative studies of coordination properties of puromycin and puromycin aminonucleoside towards copper(II) ions

Protonation equilibria of puromycin (PM) and puromycin aminonucleoside (PAN) and their coordination by copper(II) ion were studied in solution by potentiometry, electronic absorption spectroscopy (UV-Vis), circular dichroism (CD), electron paramagnetic resonance (EPR) and mass spectrometry. For puromycin four mononuclear complexes were found, with stoichiometries Cu(PM)2+, CuH(-1)(PM)+, CuH(-2)(PM) and CuH(-3)(PM)(-). In each of them the Cu(II) ion was bound in the peptidic-like manner, the differences of stoichiometries are a consequence of subsequent deprotonations of the sugar C2'-OH group and the coordinated water molecule. The coordination mode for puromycin aminonucleoside was aminosugar-like. Two dimeric complexes, Cu2H(-1)(PAN)2(2+) and Cu2H(-2)(PAN)2+, and one monomeric CuH(-2)(PAN)2 were found. The N6,N6-dimethyladenine moiety of PAN was not involved in the coordination process due to steric hindrance.     

Large Circular Dichroism in MDM Plasmonic Metasurface with Subwavelength Crescent Aperture

A metal–dielectric–metal planar chiral plasmonic metasurface is proposed and its circular dichroism (CD) property is numerically studied using finite difference time domain computation. The unit cell of planar plasmonic metasurface consists of crescent apertures that are arranged in a particular orientation. The proposed structure exhibits multiband circular dichroism at near-infrared wavelengths. By changing the orientational symmetry, the structure shows a drastic reduction in the circular dichroism. Passive controlling of orientational symmetry shows a systematic change in the sign of the CD. High incident angular tolerance of the planar chiral plasmonic metasurface (PCPM) to about 15° suggests the proposed structure might be useful for CD spectroscopy.

     

Conformational studies on chiral rhodium complexes by ECD and VCD spectroscopy

This article reports vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopic studies in acetonitrile on the chiral Rh(2)(O-Phe-Cbz)(1)(OAc)(3) and Rh(2)(O-Phe-Ac)(1)(OAc)(3) complexes (abbreviated Rh(2)Z(1) and Rh(2)Ac(1) , respectively; Phe, L-phenylalanine; Cbz, benzyloxycarbonyl; Ac, acetyl) supported by theoretical calculations. The ECD spectra of the complexes depend on temperature that indicates the conformational mobility of the chiral ligands. Calculations of the VCD spectra were performed at ab initio (DFT) level of theory using Gaussian 03 [B3LYP functional combined with the LANL2DZ basis set for the dirhodium core and the 6-31G(d) basis set for other atoms]. The population-weighted sums of the computed VCD spectra of the conformers are in excellent agreement with the experimental VCD spectra. The combination of the VCD and ECD spectroscopic methods led us to the structural characterization of the complexes.     

Exploring the scope of redox-triggered chiroptical switches: syntheses, X-ray structures, and circular dichroism of cobalt and nickel complexes of N,N-bis(arylmethyl)methionine derivatives

N,N-Bis(arylmethyl)methionine derivatives are chiral ligands whose complexes with metal ions may show molecular helicity that can be modulated by defined structural processes. It was shown previously that exciton-coupled circular dichroism (ECCD) spectral amplitude could be modulated by one-electron copper redox chemistry in copper complexes of these ligands. Here we describe the further development of novel systems that show conformational changes resulting in the inversion of exciton chirality. The phenomenon was probed in a N,N-bis(arylmethyl)methionine derivative containing quinoline/pyridine moieties and a methionine carboxylate moiety. The sign of the ECCD of the complex formed between this ligand and CoCl2 is negative, which suggests that the deprotonated carboxylate oxygen coordinates to the metal, but the sulfur atom does not. The sign of the ECCD inverts to positive upon addition of ascorbic acid, which can be turned back to negative upon further treatment with persulfate. X-ray quality crystals of three cobalt complexes and one nickel complex were obtained. The ascorbate-treated cobalt complex of the ligand and the same ligand with nickel, however, vary from the behavior expected from their X-ray crystal structures. It is clear that the solution and crystallographic structures of these complexes differ in several cases.     

Induced circular dichroism of cycloamylose complexes with meta- and para-disubstituted benzenes

Cycloamylose complexes with substituted benzenes in aqueous solutions were investigated by circular dichroism (CD) spectroscopy. The differences in CD spectra between cyclohexaamylose complexes and cycloheptaamylose complexes suggests that the orientation and disposition of the guest molecule differ in these two cycloamylose complexes. It was shown theoretically that the sign and intensity of CD are quite sensitive to the orientation of the guest chromophor in the cycloamylose cavity, but that the difference between the cyclohexaamylose complex and the cycloheptaamylose complex is only 13% if the guest molecule is included in the same geometry. Molecular ellipticity and thermodynamic parameters, which were determined by the least-squares curve-fitting procedure, indicate that the guest molecule is more closely packed in the cyclohexaamylose cavity, and that there is no stereospecificity in the complex formation between the meta-disubstituted benzenes and the para-disubstituted benzenes.     

Study of stereoselective interactions of carbamoylated quinine and quinidine with 3,5-dinitrobenzoyl α-amino acids using VCD spectroscopy in the region of C−H stretching vibrations

The stereoselective complexation of tert‐butylcarbamoyl quinine and tert‐butylcarbamoyl quinidine selectors (SOs) with 3,5‐dinitrobenzoyl (DNB) derivatives of D ‐ and L ‐alpha amino acids (DNB‐Ala, DNB‐Val, DNB‐Leu, and DNB‐Ile) as well as achiral DNB‐Gly has been studied by vibrational circular dichroism (VCD) spectroscopy in the spectral region of C H stretching vibrations. All the complexes of SOs and sterically compatible enantiomers of derivatized amino acid selectands (SAs) showed induced circular dichroism (ICD) bands in the region of aromatic C H stretching vibrations, indicating the occurrence of a π–π interaction between the aromatic moieties of SA and SO. To our knowledge, this is the first report in which a π–π interaction was observed by VCD spectroscopy in this spectral region. No ICD bands were disclosed in the spectra of the sterically incompatible SA and SO complexes. The spectral pattern in the region of aliphatic C H stretching vibrations showed interaction‐induced conformational adaptations in sterically favorable SA and SO complexes. No such spectral changes were observed for any of the sterically incompatible complexes. The DNB‐Gly complexes exhibited spectral patterns similar to those observed for sterically favorable pairs of SOs and chiral SAs. Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Anisotropic circular dichroism signatures of oriented thylakoid membranes and lamellar aggregates of LHCII

In photosynthesis research, circular dichroism (CD) spectroscopy is an indispensable tool to probe molecular architecture at virtually all levels of structural complexity. At the molecular level, the chirality of the molecule results in intrinsic CD; pigment–pigment interactions in protein complexes and small aggregates can give rise to excitonic CD bands, while “psi-type” CD signals originate from large, densely packed chiral aggregates. It has been well established that anisotropic CD (ACD), measured on samples with defined non-random orientation relative to the propagation of the measuring beam, carries specific information on the architecture of molecules or molecular macroassemblies. However, ACD is usually combined with linear dichroism and can be distorted by instrumental imperfections, which given the strong anisotropic nature of photosynthetic membranes and complexes, might be the reason why ACD is rarely studied in photosynthesis research. In this study, we present ACD spectra, corrected for linear dichroism, of isolated intact thylakoid membranes of granal chloroplasts, washed unstacked thylakoid membranes, photosystem II (PSII) membranes (BBY particles), grana patches, and tightly stacked lamellar macroaggregates of the main light-harvesting complex of PSII (LHCII). We show that the ACD spectra of face- and edge-aligned stacked thylakoid membranes and LHCII lamellae exhibit profound differences in their psi-type CD bands. Marked differences are also seen in the excitonic CD of BBY and washed thylakoid membranes. Magnetic CD (MCD) spectra on random and aligned samples, and the largely invariable nature of the MCD spectra, despite dramatic variations in the measured isotropic and anisotropic CD, testify that ACD can be measured without substantial distortions and thus employed to extract detailed information on the (supra)molecular organization of photosynthetic complexes. An example is provided showing the ability of CD data to indicate such an organization, leading to the discovery of a novel crystalline structure in macroaggregates of LHCII.     

Chirality and circular dichroism of oriented molecules and anisotropic phases

The results of the "Chirality measurement" circular dichroism along different viewing directions within molecules and phases-the anisotropy of circular dichroism can give suitable information in order to check helicity rules or to analyze the suprastructural chirality of films of organic materials, respectively. These results of the ACD spectroscopy (the CD of anisotropic phases and oriented molecules) show that in an oriented state different information about "chirality" will be gained from different viewing directions. ACD measurements of alpha,beta-unsaturated ketosteroids, TADDOLes and binaphthol derivatives were analyzed. The chiral induction of cholesteric phases, the helical twisting power, is introduced as another chirality measurement which may possibly be a new relative method for the determination of the absolute configuration. Copyright 2000 Wiley-Liss, Inc.     

Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence

Cell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denoted as PR9, greatly enhance the delivery of noncovalently associated quantum dots (QDs) into human A549 cells. Mechanistic studies, intracellular trafficking analysis and a functional gene assay reveal that endocytosis is the main route for intracellular delivery of PR9/QD complexes. Endocytic trafficking of PR9/QD complexes was monitored using both confocal and transmission electron microscopy (TEM). Zeta-potential and size analyses indicate the importance of electrostatic forces in the interaction of PR9/QD complexes with plasma membranes. Circular dichroism (CD) spectroscopy reveals that the secondary structural elements of PR9 have similar conformations in aqueous buffer at pH 7 and 5. This study of nontoxic PR9 provides a basis for the design of optimized cargo delivery that allows escape from endocytic vesicles.     

Raman study of in vivo synthesized Zn(II)-metallothionein complexes: structural insight into metal clusters and protein folding

Metallothioneins (MTs) are metal-chelating peptides that play an active role in zinc homeostasis. The participation of metal ligands other than cysteines and the presence of secondary structure elements in metal-MT complexes are fairly unknown, especially in nonvertebrate MTs. Here, four Zn(II) complexes of invertebrate MTs (mollusc, insect, nematode, and echinoderm) and the Zn(II)-MT complex of the mammalian MT1 isoform, heterologously synthesized in E. coli, were studied by analytic and spectroscopic techniques. By Raman and circular dichroism spectroscopy, new structural informations were obtained. The five analyzed MT isoforms consist largely of beta-turns with the near exclusion of alpha-helical segments. Raman spectroscopy was revealed as an useful tool, providing information about the state of the cysteine sulfur atoms (metal coordinated and oxidized), the participation of histidine in metal coordination, and the molecular environment of tyrosine residues. In all the five Zn(II)-MT studied samples, acid-labile sulfide anions were found as nonproteic ligands, since sulfide-containing and sulfide-devoid species coexisted in the corresponding preparations. Significantly, Raman bands useful as markers of sulfide bridging ligands were identified. Overall, this work illustrates how the combination of analytical and spectroscopic techniques can be a very informative approach for the analysis of in vivo-synthesized metal-MT complexes, providing new data on the metal binding behavior of MTs from the most diverse organisms.