Natural and synthetic nanovectors for cancer therapy.

Nanomaterials have been extensively studied in cancer therapy as vectors that may improve drug delivery. Such vectors not only bring numerous advantages such as stability, biocompatibility, and cellular uptake but have also been shown to overcome some cancer-related resistances. Nanocarrier can deliver the drug more precisely to the specific organ while improving its pharmacokinetics, thereby avoiding secondary adverse effects on the not target tissue. Between these nanovectors, diverse material types can be discerned, such as liposomes, dendrimers, carbon nanostructures, nanoparticles, nanowires, etc., each of which offers different opportunities for cancer therapy. In this review, a broad spectrum of nanovectors is analyzed for application in multimodal cancer therapy and diagnostics in terms of mode of action and pharmacokinetics. Advantages and inconveniences of promising nanovectors, including gold nanostructures, SPIONs, semiconducting quantum dots, various nanostructures, phospholipid-based liposomes, dendrimers, polymeric micelles, extracellular and exome vesicles are summarized. The article is concluded with a future outlook on this promising field.

Caffeic Acid, Quercetin and 5-Fluorocytidine-Functionalized Au-Fe3O4 Nanoheterodimers for X-ray-Triggered Drug Delivery in Breast Tumor Spheroids.

Au-Fe3O4 nanoheterodimers (NHD) were functionalized with the natural and synthetic anticancer drugs caffeic acid (CA), quercetin (Q) and 5-fluorocytidine (5FC). Their X-radiation dose-enhancing potential and chemotherapeutic efficacy for bimodal cancer therapy were investigated by designing multicellular tumor spheroids (MCTS) to in vitro avascular tumor models. MCTS were grown from the breast cancer cell lines MCF-7, MDA-MB-231, and MCF-10A. The MCF-7, MDA-MB-231 and MCF-10A MCTS were incubated with NHD-CA, NHD-Q, or NHD-5FC and then exposed to fractionated X-radiation comprising either a single 10 Gy dose, 2 daily single 5 Gy doses or 5 daily single 2 Gy doses. The NHD-CA, NHD-Q, and NHD-5FC affected the growth of X-ray irradiated and non-irradiated MCTS in a different manner. The impact of the NHDs on the glycolytic metabolism due to oxygen deprivation inside MCTS was assessed by measuring lactate secretion and glucose uptake by the MCTS. The NHD-CA and NHD-Q were found to act as X-radiation dose agents in MCF-7 MCTS and MDA-MB-231 MCTS and served as radioprotector in MCF-10A MCTS. X-ray triggered release of CA and Q inhibited lactate secretion and thereupon disturbed glycolytic reprogramming, whereas 5FC exerted their cytotoxic effects on both, healthy and tumor cells, after their release into the cytosol.

Smart Shell-by-Shell Nanoparticles with Tunable Perylene Fluorescence in the Organic Interlayer.

A new series of shell-by-shell (SbS)-functionalized Al2 O3 nanoparticles (NPs) containing a perylene core in the organic interlayer as a fluorescence marker is introduced. Initially, the NPs were functionalized with both, a fluorescent perylene phosphonic acid derivative, together with the lipophilic hexadecylphosphonic acid or the fluorophilic (1 H,1 H,2 H,2H-perfluorodecyl)phosphonic acid. The lipophilic first-shell functionalized NPs were further implemented with amphiphiles built of aliphatic chains and polar head-groups. However, the fluorophilic NPs were combined with amphiphiles consisting of fluorocarbon tails and polar head-groups. Depending on the nature of the combined phosphonic acids and the amphiphiles, tuning of the perylene fluorescence can be accomplished due variations of supramolecular organization with the shell interface. Because the SbS-functionalized NPs dispose excellent dispersibility in water and in biological media, two sorts of NPs with different surface properties were tested with respect to biological fluorescent imaging applications. Depending on the agglomeration of the NPs, the cellular uptake differs. The uptake of larger agglomerates is facilitated by endocytosis, whereas individualized NPs cross directly the cellular membrane. Also, the larger agglomerates were preferentially incorporated by all tested cells.

Pt-Fe3O4, Pd-Fe3O4, and Au-Fe3O4 Nanoheterodimers and Their Efficacy as Radiosensitizers in Cancer Therapy.

The X-radiation enhancing effect of caffeic acid-functionalized Au-Fe3O4, Pt-Fe3O4, and Pd-Fe3O4 nanoheterodimers (NHDs) on 2D and 3D breast tumor (MCF-7) and healthy breast epithelial (MCF-10A) cells was comprehensively examined by performing cell viability, reactive oxygen species (ROS) detection, enzyme activity, and clonogenic assays. Intracellular NHDs were observed to cause DNA fragmentation and to enhance superoxide and hydroxyl radical formation in MCF-7 cells when exposed to a single dose of 1 Gy. MCF-7-derived multicellular tumor spheroids (MCF-7 MCTS) and MCF-10A-derived multicellular spheroids (MCF-10A MCS) were incubated with the NHDs and irradiated with five daily doses of 2 Gy. The Au-Fe3O4 and Pt-Fe3O4 NHD-loaded MCF-7 MCTS significantly decreased in volume after being exposed to fractionated irradiation, whereas intracellular Au-Fe3O4 and Pt-Fe3O4 NHDs promoted the growth of the irradiated MCF-10A MCS. Moreover, Au-Fe3O4 and Pt-Fe3O4 NHDs were shown to impede ROS formation and inhibit DNA strand breakage in the noncancerous MCF-10A cells. On the other hand, the Pd-Fe3O4 NHDs boosted X-radiation-induced damage of MCF-10 A cells, which was ascribed to impairment of the ROS scavenging enzyme activities. In summary, caffeic acid-functionalized Au-Fe3O4 and Pt-Fe3O4 NHDs performed as excellent X-radiation enhancing agents in breast tumor cells, while they protect healthy breast epithelial cells against X-radiation.

Bifunctional Au-Fe3O4 Nanoheterodimers Acting as X-ray Protector in Healthy Cells and as X-ray Enhancer in Tumor Cells.

Bifunctional Au-Fe3O4 nanoheterodimers were synthesized by thermally decomposing Fe(III)oleate on gold nanoparticles followed by functionalizing with tiron, 2,3-dihydroxybenzoic acid, or caffeic acid. These catechol derivatives are antioxidative and thus are predicted to function as superoxide scavengers. In particular, caffeic acid lost its antioxidant capacity, although it was covalently linked through its carboxyl moiety to the Fe3O4 surface. Tiron was shown to bind via its catechol group to the Au-Fe3O4 nanoheterodimers, and 2,3-dihydroxybenzoic was just physisorbed between the oleic acid surface structures. Caffeic-acid stabilized Au-Fe3O4 nanoheterodimers turned out to act as X-ray protector in healthy cells but as X-ray enhancing agents in cancer cells. Furthermore, these functionalized Au-Fe3O4 nanoheterodimers were found to inhibit the migratory capacity of the cancer cells.

Determination of the two-dimensional distributions of gold nanorods by multiwavelength analytical ultracentrifugation.

Properties of nanoparticles are influenced by various parameters like size, shape or composition. Comprehensive high throughput characterization techniques are urgently needed to improve synthesis, scale up to production and make way for new applications of multidimensional particulate systems. In this study, we present a method for measuring two-dimensional size distributions of plasmonic nanorods in a single experiment. Analytical ultracentrifuge equipped with a multiwavelength extinction detector is used to record the optical and sedimentation properties of gold nanorods simultaneously. A combination of sedimentation and extinction properties, both depending on diameter and length of the dispersed nanorods, is used to measure two-dimensional distributions of gold nanorod samples. The length, diameter, aspect ratio, volume, surface and cross-sectional distributions can be readily obtained from these results. As the technique can be extended to other non-spherical plasmonic particles and can be used for determining relative amounts of particles of different shapes it provides complete and quantitative insights into particulate systems.

NOBF4-Functionalized Au-Fe3O4 Nanoheterodimers for Radiation Therapy: Synergy Effect Due to Simultaneous Reactive Oxygen and Nitrogen Species Formation.

Snowman-shaped Au-Fe3O4 nanoheterodimers were synthesized by thermal decomposition of iron oleate on presynthesized Au nanoparticles. Subsequently performed ligand exchange with nitrosyl tetrafluoroborate provided water solubility and enabled X-ray-induced NO release. These Au-Fe3O4 nanoheterodimers combine high- Z material with catalytically active Fe3O4 surfaces and, moreover, plasmonic properties with superparamagnetic performance. We could establish synergetic interactions between X-radiation and both the Au and Fe3O4 surfaces, which resulted in the simultaneous production of the nitric oxide radical at the Fe3O4 surface and the superoxide radical at the Au surface. The surface-confined reaction between these radicals generated peroxynitrite. This highly reactive species may cause nitration of mitochondrial proteins and lipid peroxidation and induce DNA strand breaks. Therefore, high concentrations of peroxynitrite are expected to give rise to severe cellular energetic derangements and thereupon entail rapid cell death. As providing a common platform for X-ray-induced formation of the highly reactive radical nitric oxide, superoxide, and peroxynitrite, nitrosyl tetrafluoroborate functionalized Au-Fe3O4 nanosnowmen were shown to exhibit excellent performance as X-ray-enhancing agents in radiation therapy.

Enhanced In Vitro Biocompatibility and Water Dispersibility of Magnetite and Cobalt Ferrite Nanoparticles Employed as ROS Formation Enhancer in Radiation Cancer Therapy.

Efficient magnetic reactive oxygen species (ROS) formation enhancing agents after X-ray treatment are realized by functionalizing superparamagnetic magnetite (Fe3 O4 ) and Co-ferrite (CoFe2 O4 ) nanoparticles with self-assembled monolayers (SAMs). The Fe3 O4 and CoFe2 O4 nanoparticles are synthesized using Massart's coprecipitation technique. Successful surface modification with the SAM forming compounds 1-methyl-3-(dodecylphosphonic acid) imidazolium bromide, or (2-{2-[2-hydroxy-ethoxy]-ethoxy}-ethyl phosphonic acid provides biocompatibility and long-term stability of the Fe3 O4 and CoFe2 O4 nanoparticles in cell media. The SAM-stabilized ferrite nanoparticles are characterized with dynamic light scattering, X-ray powder diffraction, a superconducting quantum interference device, Fourier transform infrared attenuated total reflectance spectroscopy, zeta potential measurements, and thermogravimetric analysis. The impact of the SAM-stabilized nanoparticles on the viability of the MCF-7 cells and healthy human umbilical vein endothelial cells (HUVECs) is assessed using the neutral red assay. Under X-ray exposure with a single dosage of 1 Gy the intracellular SAM stabilized Fe3 O4 and CoFe2 O4 nanoparticles are observed to increase the level of ROS in MCF-7 breast cancer cells but not in healthy HUVECs. The drastic ROS enhancement is associated with very low dose modifying factors for a survival fraction of 50%. This significant ROS enhancement effect by SAM-stabilized Fe3 O4 and CoFe2 O4 nanoparticles constitutes their excellent applicability in radiation therapy.

APTES-Terminated ultrasmall and iron-doped silicon nanoparticles as X-Ray dose enhancer for radiation therapy.

Silicon nanoparticles with sizes between were synthesized through wet-chemistry procedures using diverse phase transfer reagents. On the other hand, the preparation of iron-doped silicon nanoparticles was carried out using the precursor Na4Si4 containing 5% Fe. Biocompatibility of all silicon nanoparticle samples was achieved by surface-stabilizing with (3-aminopropyl)triethoxysilane. These surface structures provided positive surface charges which facilitated electrostatic binding to the negatively charged biological membranes. The mode of interaction with membranes, being either incorporation or just attachment, was found to depend on the nanoparticle size. The smallest silicon nanoparticles (ca. 1.5 nm) were embedded in the mitochondrial membrane in MCF-7 cells. When interacting with X-rays these silicon nanoparticles were observed to enhance the superoxide formation upon depolarizing the mitochondrial membrane. X-ray irradiation of MCF-7 cells loaded with the larger silicon nanoparticles was shown to increase the intracellular singlet oxygen generation. The doping of the silicon nanoparticles with iron led to additional production of hydroxyl radicals via the Fenton reaction.

Understanding the Role of Surface Charge in Cellular Uptake and X-ray-Induced ROS Enhancing of Au-Fe3O4 Nanoheterodimers.

Au-Fe3O4 nanoheterodimers were obtained by thermally decomposing iron oleate on presynthesized gold nanoparticles. Water solubility as well as surface charges were achieved by encapsulating the initially hydrophobic Au-Fe3O4 nanoheterodimers in a self-assembled bilayer shell formed either by 1-octadecylpyridinium, providing positive surface charges, or by 4-dodecylbenzenesulfonate, yielding a negatively charged surface. The surface charge and surface architecture were shown to control both the cellular entry and the intracellular trafficking of the Au-Fe3O4 nanoheterodimers. The positively charged (1-octylpyridinium-terminated) Au-Fe3O4 nanoheterodimers were internalized by both breast cancer cells (MCF-7) and epithelial cells (MCF-10 A), wherein they were electrostatically bound at the negatively charged membranes of the cell organelles and, in particular, adsorbed onto the mitochondrial membrane. The treatment of MCF-7 and MCF-10 cells with a fractional X-radiation dose of 1 Gy resulted into a large increase of superoxide production, which arose from the Au-Fe3O4 nanoheterodimer-induced mitochondrial depolarization. In contrast, the negatively charged (4-dodecylbenzenesulfonate-terminated) Au-Fe3O4 nanoheterodimers preferentially invaded the cancerous MCF-7 cells by direct permeation. X-ray treatment of MCF-7 cells, loaded with anionic Au-Fe3O4 nanoheterodimers, yielded the increase of both hydroxyl radical and cytoplasmic superoxide formation. The X-radiation-induced activation of the Fe3O4 surfaces, consisting of Fe2+ and Fe3+ cations, triggered the catalysis of the hydroxyl radical production, whereas superoxide formation presumably occurred through X-ray-induced photoelectron emission near the Au surface. Since hydroxyl radicals are highly cytotoxic and the negatively charged Au-Fe3O4 NHDs spare the healthy MCF-10A cells, these Au-Fe3O4 nanoheterodimers exhibit a higher potential for radiation therapy than the positively charged Au-Fe3O4 nanoheterodimers. Encouraging results from the clonogenic cell survival assay and DMF calculations corroborate the excellent performance of the anionic Au-Fe3O4 nanoheterodimers as an X-ray dosage enhancer.

Surface Functionalization and Electrical Discharge Sensitivity of Passivated Al Nanoparticles.

Passivated aluminum nanoparticles are surface functionalized to elucidate their sensitivity against an electrical discharge. Two size fractions that differ in surface morphology are investigated. Electronic interactions between the partly inert, partly energetic organic molecules used for surface functionalization and the alumina surface are analyzed in detail. The nanoparticle surfaces are modified with the well-established, inert 2-[2-(2-methoxyethoxy)ethoxy]acetic acid, whereas energetic surface modification is achieved using 1,3,5-trinitroperhydro-1,3,5-triazine or the acidic and aromatic 2,4,6-trinitrophenol. A mechanistic model for the chemical surface functionalization of Al nanoparticles is hypothesized and corroborated by comprehensive optical and Fourier transform infrared spectroscopy studies. The surface structures are adjusted by developing a tunable stabilization procedure that prevents sedimentation and hence increases the saturation concentration in the liquid phase and finally affects the sensitivity character in view of electrical discharge ignition of dry powders. Detailed material characterization is conducted using transmission electron microscopy, combined with energy-dispersive X-ray spectroscopy and various absorption spectroscopy techniques (steady state in the infrared and ultraviolet/visible regime). The adjustment of surface structures of the distinct Al nanoparticle samples offers a valuable tool for tuning and tailoring the reactivity, sensitivity, stability, and energetic performances of the nanoparticles, and thereby enables the safe use of these multipurpose nanoparticles.

Improved photocatalytic activity of gold decorated differently doped TiO2 nanoparticles: A comparative study.

In this paper, undoped and several differently doped (with Fe(3+), N(-), and γ-Al2O3) TiO2-nanoparticle-based photocatalysts and those covered with ultrasmall gold nanoparticles (AuNPs) were engineered. Their photocatalytic performance was studied by utilizing them for the liquid-phase decomposition of the model dye methylene blue (MB) under visible-light irradiation. The structural, morphological, physico-chemical, and optical properties of the photocatalysts were investigated using X-ray diffraction, X-ray photoelectron spectroscopy, diffuse-reflectance UV-Vis absorption spectroscopy, Raman spectroscopy and transmission electron microscopy. Photodegradation kinetics of MB was followed by measuring the absorbance of MB at 664 nm at different irradiation times, whereas the mineralization of MB was examined by determining the total organic carbon (TOC) content. The photocatalytic activity of TiO2 nanoparticles was shown to be significantly increased by introducing dopants into the crystal lattice and depositing AuNPs on the surface. Among those, γ-Al2O3 doped TiO2 nanoparticles covered with deposited AuNPs show the best photocatalytic performance. Altogether, the here engineered photocatalysts as consisting of doped TiO2 nanoparticles decorated with AuNPs establish novel three-component nanocomposite systems, where synergetic interactions between surface AuNPs, dopants and TiO2 were shown to significantly enhance the photocatalytic activity.

A facile one-pot synthesis of blue and red luminescent thiol stabilized gold nanoclusters: a thorough optical and microscopy study.

Here in this contribution, blue and red luminescent 1-dodecanethiol (DT) terminated gold nanoclusters (AuNC) were prepared by a simple two-step synthesis route where the first step involved the surfactant-free synthesis of bare AuNC in N,N'-dimethylformamide (DMF) and the second step is the termination of the as-prepared bare AuNC by 1-dodecanethiol. The blue and red luminescent DT-terminated AuNC were isolated by a solvent-induced precipitation followed by an ultra-centrifugation technique. Both the bare AuNC and the blue and red luminescent DT-terminated AuNC exhibit stable photoluminescence and good solubility in various solvents. The photo-physical, electronic, structural, and morphological properties of the bare AuNC and the blue and red luminescent DT-terminated AuNC were examined by performing UV-Vis absorption spectroscopy, stationary and time-resolved PL spectroscopy, X-ray photoelectron spectroscopy (XPS), femtosecond transient absorption spectroscopy, Fourier-transform infrared spectroscopy (FTIR-ATR), and high-resolution transmission electron microscopy (HRTEM) experiments.

A facile synthesis of highly stable and luminescent Ag clusters: a steady-state and time-resolved spectroscopy study.

In this paper, we reported a very simple and environmentally friendly procedure for the synthesis of bright luminescent and nearly monodisperse Ag nanoclusters stabilized by a poly(N-vinylpyrrolidone) homopolymer. In this synthesis route acetonitrile or N,N-dimethylformamide (DMF) acts as both solvent and a reducing agent at their respective reflux temperatures. The as-prepared Ag clusters were found to be highly stable in various solvents as well as show nearly no changes in their emission intensity in solutions with different pH values and ionic strengths. Remarkably, the acetonitrile method predominantly produces blue emitting Ag clusters with a photoluminescence (PL) emission maximum at 424 nm (quantum yield 3.5%), whereas mainly blue-green emitting Ag clusters with the PL emission maximum at 450 nm (quantum yield 2.7%) were formed using the DMF method. The photo-physical, electronic, structural and morphological properties of the Ag clusters were investigated by performing UV/Vis absorption spectroscopy, stationary and time-resolved PL spectroscopy, X-ray photoelectron spectroscopy, femtosecond transient absorption spectroscopy, and transmission electron microscopy experiments.

Superparamagnetic iron oxide nanoparticles as novel X-ray enhancer for low-dose radiation therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) with a mixed phase composition (γ-Fe2O3)(1-x)(Fe3O4)x and sizes between 9 and 20 nm were synthesized via coprecipitation and were either left uncoated or subsequently surface-stabilized with citrate or malate anions. The sizes, morphology, surface chemistry, and magnetic properties of the nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and superconducting quantum interference device measurements, respectively. Cellular uptake and intracellular distribution in normal tissue and tumor cells were verified by TEM images. X-ray-induced changes of the oxidation state and site geometries of surface iron ions of uncoated and citrate-coated SPIONs were explored by collecting Fe K-edge X-ray absorption spectroscopy data. The potential applicability of citrate- and malate-coated SPIONs as an X-ray enhancer for radiation cancer therapy was substantiated by their drastic enhancement of the concentration of reactive oxygen species (ROS) in X-ray irradiated tumor cells.

Metallic-like stoichiometric copper sulfide nanocrystals: phase- and shape-selective synthesis, near-infrared surface plasmon resonance properties, and their modeling.

In the realm of semiconductor nanomaterials, a crystal lattice heavily doped with cation/anion vacancies or ionized atomic impurities is considered to be a general prerequisite to accommodating excess free carriers that can support localized surface plasmon resonance (LSPR). Here, we demonstrate a surfactant-assisted nonaqueous route to anisotropic copper sulfide nanocrystals, selectively trapped in the covellite phase, which can exhibit intense, size-tunable LSPR at near-infrared wavelengths despite their stoichiometric, undoped structure. Experimental extinction spectra are satisfactorily reproduced by theoretical calculations performed by the discrete dipole approximation method within the framework of the Drude-Sommerfeld model. The LSPR response of the nanocrystals and its geometry dependence are interpreted as arising from the inherent metallic-like character of covellite, allowed by a significant density of lattice-constitutional valence-band free holes. As a consequence of the unique electronic properties of the nanocrystals and of their monodispersity, coherent excitation of symmetric radial breathing modes is observed for the first time in transient absorption experiments at LSPR wavelengths.

Oxidized silicon nanoparticles for radiosensitization of cancer and tissue cells.

The applicability of ultrasmall uncapped and aminosilanized oxidized silicon nanoparticles (SiNPs and NH2-SiNPs) as radiosensitizer was studied by internalizing these nanoparticles into human breast cancer (MCF-7) and mouse fibroblast cells (3T3) that were exposed to X-rays at a single dose of 3 Gy. While SiNPs did not increase the production of reactive oxygen species (ROS) in X-ray treated cells, the NH2-SiNPs significantly enhanced the ROS formation. This is due to the amino functionality as providing positive surface charges in aqueous environment. The NH2-SiNPs were observed to penetrate into the mitochondrial membrane, wherein these nanoparticles provoked oxidative stress. The NH2-SiNPs induced mitochondrial ROS production was confirmed by the determination of an increased malondialdehyde level as representing a gauge for the extent of membrane lipid peroxidation. X-ray exposure of NH2-SiNPs incubated MCF-7 and 3T3 cells increased the ROS concentration for 180%, and 120%, respectively. Complementary cytotoxicity studies demonstrate that these silicon nanoparticles are more cytotoxic for MCF-7 than for 3T3 cells.

Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation.

Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces.

Monitoring biological membrane-potential changes: a CI QM/MM study.

In recent decades, new less-invasive, nonlinear optical methods have been proposed and optimized for monitoring fast physiological processes in biological cells. One of these methods allows the action potential (AP) in cardiomyocytes or neurons to be monitored by means of second-harmonic generation (SHG). We now present the first, to our knowledge, simulations of the dependency of the intensity of the second harmonic (I(SHG)) on variations of the transmembrane potential (TMP) in a cardiomyocyte during an action potential (AP). For this, an amphiphilic potential-sensitive styryl dye molecule with nonlinear optical properties was embedded in a dipalmitoylphosphatidylcholine (DPPC) bilayer, replacing one of the phospholipid molecules. External electrical fields with different strengths were applied across the membrane to simulate the AP of a heart-muscle cell. We used a combined classical/quantum mechanical approach to model the structure and the spectroscopic properties of the embedded chromophore. Two 10 ns molecular dynamics (MD) simulations provided input geometries for semiempirical molecular orbital (QM/MM) single-point configuration interaction (CI) calculations, which were used to calculate the wavelengths and oscillator strengths of electronic transitions in the di-8-ANEPPS dye molecule. The results were then used in a sum-over-states treatment to calculate the second-order hyperpolarizability. The square of the hyperpolarizability scales with the intensity of the second harmonic, which is used to monitor the action potentials of cardiomyocytes experimentally. Thus, we computed changes in the intensity of the second harmonic (DeltaI(SHG)) as function of TMP changes. Our results agree well with experimental measurements.

Bis-chelated imine-alkoxytitanium complexes: novel chiral dopants with high helical twisting power in liquid crystals.

Enantiomerically and diastereomerically pure bis-chelated imine-alkoxytitanium complexes 6 and 7 have been synthesized and used as chiral dopants for converting nematic into cholesteric phases. The dopants were tested in mainly commercially available nematic liquid crystalline compounds or mixtures: LC1 (BASF), ZLI-1695 and ZLI-1840 (Merck), as well as N-(4-methoxybenzylidene)-4'-butylaniline (MBBA). The values of the helical twisting power (HTP) were determined by the Grandjean-Cano method. Exceptionally high helical twisting powers were obtained. Thus, the titanium complex 6 h displayed a HTP value of 740 microm(-1) in MBBA, the highest HTP value reported. The helical twisting power has been found to depend strongly on the structure of the nematic phase and the substitution pattern of the chiral ligand in the titanium complexes 6 and 7. Crystal structure analysis of 6 f confirmed the A,R,R configuration of the metal complex. The chiral imine ligands 4 and 5 were derived from the regioisomeric amino alcohols 1 and 2.