Anticancer cyclometalated [Au(III)m(C(wedge)N(wedge)C)mL]n+ compounds: Synthesis and cytotoxic properties

A series of cyclometalated gold(III) compounds [Au(m)(C(wedge)N(wedge)C)mL]n+ (m = 1-3; n = 0-3; HC(wedge)N(wedge)CH = 2,6-diphenylpyridine) was prepared by ligand substitution reaction of L with N-donor or phosphine ligands. The [Au(m)(C(wedge)N(wedge)C)mL]n+ compounds are stable in solution in the presence of glutathione. Crystal structures of the gold(III) compounds containing bridging bi- and tridentate phosphino ligands reveal the presence of weak intramolecular pi pi stacking between the [Au(C(wedge)N(wedge)C)]+ units. Results of MTT assays demonstrated that the [Au(m)(C(wedge)N(wedge)C)mL]n+ compounds containing nontoxic N-donor auxiliary ligands (2) exert anticancer potency comparable to that of cisplatin, with IC50 values ranging from 1.5 to 84 microM. The use of [Au(C(wedge)N(wedge)C)(1-methylimidazole)]+ (2 a) as a model compound revealed that the gold(III)-induced cytotoxicity occurs through an apoptotic cell-death pathway. The cell-free interaction of 2 a with double-stranded DNA was also examined. Absorption titration showed that 2 a binds to calf-thymus DNA (ctDNA) with a binding constant of 4.5 x 10(5) dm3 mol(-1) at 298 K. Evidence from gel-mobility-shift assays and viscosity measurements supports an intercalating binding mode for the 2 a-DNA interaction. Cell-cycle analysis revealed that 2 a causes S-phase cell arrest after incubation for 24 and 48 hours. The cytotoxicity of 3 b-g toward cancer cells (IC50 = 0.04-4.3 microM) correlates to that of the metal-free phosphine ligands (IC50 = 0.1-38.0 microM), with [Au2(C(wedge)N(wedge)C)2(mu-dppp)]2+ (3 d) and dppp (dppp = 1,2-bis(diphenylphosphino)propane) being the most cytotoxic gold(III) and metal-free compounds, respectively. Compound 3 d shows a cytotoxicity at least ten-fold higher than the other gold(III) analogues; in vitro cellular-uptake experiments reveal similar absorptions for all the gold(III) compounds into nasopharyngeal carcinoma cells (SUNE1) (1.18-3.81 ng/cell; c.f., 3 d = 2.04 ng/cell), suggesting the presence of non-gold-mediated cytotoxicity. Unlike 2 a, both gold(III) compounds [Au(C(wedge)N(wedge)C)(PPh3)]+ (3 a) (PPh3 = triphenylphosphine) and [Au2(C(wedge)N(wedge)C)2(mu-dppp)]2+ (3 d) interact only weakly with ctDNA and do not arrest the cell cycle.     

Wave envelopes method for description of nonlinear acoustic wave propagation

A novel, free from paraxial approximation and computationally efficient numerical algorithm capable of predicting 4D acoustic fields in lossy and nonlinear media from arbitrary shaped sources (relevant to probes used in medical ultrasonic imaging and therapeutic systems) is described. The new WE (wave envelopes) approach to nonlinear propagation modeling is based on the solution of the second order nonlinear differential wave equation reported in [J. Wójcik, J. Acoust. Soc. Am. 104 (1998) 2654-2663; V.P. Kuznetsov, Akust. Zh. 16 (1970) 548-553]. An incremental stepping scheme allows for forward wave propagation. The operator-splitting method accounts independently for the effects of full diffraction, absorption and nonlinear interactions of harmonics. The WE method represents the propagating pulsed acoustic wave as a superposition of wavelet-like sinusoidal pulses with carrier frequencies being the harmonics of the boundary tone burst disturbance. The model is valid for lossy media, arbitrarily shaped plane and focused sources, accounts for the effects of diffraction and can be applied to continuous as well as to pulsed waves. Depending on the source geometry, level of nonlinearity and frequency bandwidth, in comparison with the conventional approach the Time-Averaged Wave Envelopes (TAWE) method shortens computational time of the full 4D nonlinear field calculation by at least an order of magnitude; thus, predictions of nonlinear beam propagation from complex sources (such as phased arrays) can be available within 30-60 min using only a standard PC. The approximate ratio between the computational time costs obtained by using the TAWE method and the conventional approach in calculations of the nonlinear interactions is proportional to 1/N2, and in memory consumption to 1/N where N is the average bandwidth of the individual wavelets. Numerical computations comparing the spatial field distributions obtained by using both the TAWE method and the conventional approach (based on a Fourier series representation of the propagating wave) are given for circular source geometry, which represents the most challenging case from the computational time point of view. For two cases, short (2 cycle) and long (8 cycle) 2 MHz bursts, the computational times were 10 min and 15 min versus 2 h and 8 h for the TAWE method versus the conventional method, respectively.     

Real-time kinetics of surfactant molecule transfer between emulsion particles probed by in situ second harmonic generation spectroscopy

Emulsions are widely used in industrial and environmental remediation applications. The breaking and reformulation of emulsions, which occur during their use, lead to changes in their surface composition as well as their physical and chemical properties. Hence, a fundamental understanding of the transfer of surfactant molecules between emulsion particles is required for optimization of their applications. However, such an understanding remains elusive because of the lack of in situ and real-time surface-specific techniques. To address this, we designed and synthesized the surfactant probe molecules MG-butyl-1 (2) and MG-octyl-1 (3), which contain an n-butyl and an n-octyl chain, respectively, and a charged headgroup similar to that in malachite green (MG, 1). MG is known to be effective in generating second harmonic generation (SHG) signals when adsorbed onto surfaces of colloidal microparticles. Making use of the coherent nature of SHG, we monitored in real-time the transfer of 2 and 3 between oil-in-water emulsion particles with diameters of ~220 nm. We found that 3 is transferred ~600 times slower than 2, suggesting that an increase in the hydrophobic chain length decreases the transfer rate. Our results show that SHG combined with molecular design and synthesis of surfactant probe molecules can be used to measure the rate of surfactant transfer between emulsion particles. This method provides an experimental framework for examining the factors controlling the kinetics of surfactant transfer between emulsion particles, which cannot be readily investigated in situ and in real-time using conventional methods.     

Nanosilica-supported polyethoxyamines as low-cost, reversible carbon dioxide sorbents

Nanoparticles capped with amine ligands with different steric properties, dodecylamine and oleylamine, respectively, are investigated in the solid state as well as in solution. A combined X-ray diffraction, small angle X-ray scattering and electron microscopy investigation showed that the nanoparticles exhibit the sphalerite modification of ZnS as crystal phase with a diameter of 3-5 nm. A close packing of the monocrystalline nanoparticles in the solid state is observed. However, in the dodecylamine sample, besides spherical particles, a fraction of the nanoparticles is elongated. The nanoparticles are readily resoluble in apolar solvents like hexane. Dynamic light scattering (DLS) and SAXS investigations of the solutions reveal that the nanoparticles are dissolved as singular particles. In the case of oleylamine-capped ZnS, a defined core-shell structure with a ZnS core with a diameter of 4 nm and an organic shell with a thickness of approximately 2 nm have been found. Dodecylamine-capped nanoparticles slightly tend to form agglomerates with a diameter of approximately 40 nm.     

Safety Analysis: Relative Risks of Ultraviolet Exposure from Fluorescence Spectroscopy and Colposcopy Are Comparable*

Fluorescence spectroscopy is a promising tool for use in the diagnosis of disease in human tissue. However, few published reports have evaluated the safety of this technique, despite the fact that many spectroscopic systems use UV illumination. This study determined the relative risk associated with light exposure from spectroscopic systems compared with the traditional light sources that are used to illuminate tissue and direct biopsies. We compared spectroscopic detection systems for the cervix to the colposcope, a low-power microscope routinely used to illuminate the cervix, which does not cause any known photochemical damage. We measured the average spectral irradiance (W/[cm²nm]) and the average tissue exposure time during a diagnostic colposcopy examination. To quantify the relative risks, we multiplied illumination spectra by several action spectra from the literature and compared the areas under the curves corresponding to each procedure. The risk associated with the average power colposcope served as our basis for comparison. We conclude that the risks of illumination using spectroscopic systems are lower than or comparable to those already encountered in routine diagnostic procedures such as colposcopy with an average power colposcope. Spectroscopic examination can be associated with a somewhat higher risk than a colposcopy with the lowest power colposcope or a shorter than average colposcopy. The analysis presented can be repeated to estimate the magnitude of risks associated with other spectroscopic diagnostic devices.     

Structure and stability of Ne+He(n): experiment and diffusion quantum Monte Carlo theory with "on the fly" electronic structure

New data are reported for the mass-spectrometry fragmentation patterns of helium clusters, either pure or containing a Ne or an Ar atom. The patterns for He(n)+ and Ar+He(n) show clear evidence of structure, while those of Ne+He(n) do not. To better understand the surprising result for the Ne+He(n) fragments, diffusion quantum Monte Carlo (DMC) calculations of the energies and structural properties of these ions were performed using a diatomics-in-molecule (DIM) parametrization of the potential energy. Using DIM for electronic energy evaluation allows us to sample 10(9) configurations even for a cluster as large as Ne+He14. The results of the DMC calculation are very surprising. For n > 7, the DMC random walkers rarely venture within 100 cm(-1) of the minimum potential energy. Analysis of the resulting particle density distributions shows that the zero-point energy does more than spread the wave function around the potential-energy minima, resulting in very diffuse wave functions. For some of the clusters the quantum effects nearly exclude the region of the potential minimum from the overall wave function. An important result of this effect is that the incremental bonding energy of the nth helium atom varies quite smoothly with n, for n > 5. This eliminates the expected shell structure and explains the lack of magic-number-type features in the data.     

One-step synthesis of low polydispersity, biotinylated poly(N-isopropylacrylamide) by ATRP

Low polydispersity poly(N-isopropylacrylamide) with a biotin end-group was obtained in one step from a biotinylated initiator for atom transfer radical polymerization and interacted with streptavidin to generate the thermosensitive polymer-protein conjugate.     

Preparation and crystallographic characterization of a new endohedral,Lu3N@C80.5 (o-xylene), and comparison with Sc3N@C80.5 (o-xylene)

The trimetallic nitride template (TNT) approach has been successfully utilized to prepare the new endohedral Lu(3)N@C(80). Well-ordered crystals of Lu(3)N@C(80).5 (o-xylene) and Sc(3)N@C(80).5 (o-xylene) form upon cooling of o-xylene solutions of these endohedrals and they are isomorphous. Although the positions of the fullerene cage (which is fully ordered and located at a crystallographic center of symmetry) and the o-xylene molecules are nearly identical in these two structures, the positioning of the metal ions in the two crystals differ in significant ways. However, the expected difference in sizes of lutetium and scandium does not affect the dimensions of the C(80) cage. Nevertheless, the positions of the metal atoms do produce a slight outward dislocation of the immediately adjacent carbon atoms.