Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60

Identification of the molecular target(s) of anticancer metal complexes is a formidable challenge since most of them are unstable toward ligand exchange reaction(s) or biological reduction under physiological conditions. Gold(III) meso‐tetraphenylporphyrin ( gold‐1 a ) is notable for its high stability in biological milieux and potent in vitro and in vivo anticancer activities. Herein, extensive chemical biology approaches employing photo‐affinity labeling, click chemistry, chemical proteomics, cellular thermal shift, saturation‐transfer difference NMR, protein fluorescence quenching, and protein chaperone assays were used to provide compelling evidence that heat‐shock protein 60 (Hsp60), a mitochondrial chaperone and potential anticancer target, is a direct target of gold‐1 a in vitro and in cells. Structure–activity studies with a panel of non‐porphyrin gold(III) complexes and other metalloporphyrins revealed that Hsp60 inhibition is specifically dependent on both the gold(III) ion and the porphyrin ligand.     

Cyclometalated Palladium(II) N‐Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression

Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N‐heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N′‐nBu₂NHC)](CF₃SO₃) ( Pd1 d , HC^N^N=6‐phenyl‐2,2′‐bipyridine, N,N′‐nBu₂NHC=N,N′‐di‐n‐butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC₅₀=0.09–0.5 μm ) but is less cytotoxic toward a normal human fibroblast cell line (CCD‐19Lu, IC₅₀=11.8 μm ). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.     

The use of a [4 + 2] cycloaddition reaction for the preparation of a series of 'tethered' Ru(II)-diamine and aminoalcohol complexes

A series of catalysts have been prepared for use in the asymmetric transfer hydrogenation of ketones. The complexes were prepared using a [4 + 2] cycloaddition reaction at a key step in the reaction sequence. This provides a means for the synthesis of catalysts with modifications at specific sites.     

Interactive hidden Markov models and their applications

^** Email: wching{at}hkusua.hku.hk In this paper, we propose an Interactive hidden Markov model(IHMM). In a traditional HMM, the observable states are affecteddirectly by the hidden states, but not vice versa. In the proposedIHMM, the transitions of hidden states depend on the observablestates. We also develop an efficient estimation method for themodel parameters. Numerical examples on the sales demand dataand economic data are given to demonstrate the applicabilityof the model.     

CMOS-compatible light-emitting devices based on thin aluminum nitride film containing Al nanocrystals

Electroluminescence (EL) from Al-rich AlN thin films grown on p-type Si substrate by radio frequency (RF) magnetron sputtering has been observed at room temperature. The light-emitting structure based on the thin films can be driven by an electrical pulse as short as 10⁻⁵ s. No obvious change in the light emission intensity was observed after 10⁶ pulse cycles. It has been found that the light emission intensity increases with the Al concentration. It is shown that the phenomenon is due to the enhancement of the percolative conduction via the Al nanocrystals distributed in the AlN matrix as a result of the increase in Al concentration.     

Dynamic modelling of an intermittent slider–crank mechanism

This paper investigates kinematic and dynamic analyses of a novel intermittent slider–crank mechanism, which consists of four parts: a crank, a connecting rod associated with a pneumatic cylinder, a slider and two stops at both ends of a stroke. When the crank rotates continuously, the slider will contact with the stops and the pneumatic cylinder is compressed or extended. One periodic motion of the intermittent slider–crank mechanism driven by a permanent magnetic (PM) synchronous servomotor could be divided into three stages. Three governing equations are formulated by Hamilton’s principle. A spring model instead of the pneumatic cylinder is also used for comparison. Finally, the transient amplitudes obtained by using Runge–Kutta method are compared with those of the conventional slider–crank mechanism.     

Anion effect on the nanostructure of a metal ion binding self-assembling peptide

Effects of copper salts containing different anions (SO(4)(2)(-), Cl(-), and NO(3)(-)) on the self-assembly of a designed peptide EAK16(II)GGH with affinity for Cu(2+) have been investigated. The peptide secondary structure, self-assembled nanostructures, and surface activity were observed to depend strongly on the type of anion. Over a salt concentration range from 0.05 to 10.0 mM, SO(4)(2)(-) induced long fiber formation, whereas Cl(-) and NO(3)(-) caused short fiber formation. The fiber length increased with copper sulfate concentration, but the concentration of copper chloride and copper nitrate did not affect the peptide nanostructures significantly. Analysis by Fourier transform infrared spectroscopy (FTIR) revealed that the addition of the copper salts tended to cause the peptide conformation to change from alpha-helix/random coil to beta-sheet, the extent to which depended on the anion type. This evidence of the anion effect was also supported by surface tension measurements using the axisymmetric drop shape analysis-profile (ADSA-P) technique. An explanation for the effect of anions on the peptide self-assembly was proposed. The divalent anion SO(4)(2)(-) might serve as a bridge by electrostatically interacting with two lysine residues from different peptide molecules, promoting beta-sheet formation. The extensive beta-sheet formation may further promote peptide self-assembly into long fibers. On the other hand, monovalent anions Cl(-) and NO(3)(-) may only electrostatically interact with one charged residue of the peptide; hence, a mixed secondary structure of alpha-helix/random coil and beta-sheet was observed. This observation might explain the predominant formation of short fibers in copper chloride and copper nitrate solutions.     

Surface complexation mechanism and modeling in Cr(III) biosorption by a microalgal isolate, Chlorella miniata

The mechanism involved in the removal of Cr(III) by a green microalgal isolate, Chlorella miniata, was examined based on a series of batch experiments and microscopic analyses, and a mathematical model was proposed. Results showed that Cr(III) biosorption increased with the increase of pH from 2.0 to 4.5, and no significant changes in biosorption outside this pH range. Langmuir isotherm indicated that the maximum Cr(III) sorption capacity of Chlorella miniata was 14.17, 28.72, and 41.12 mg g(-1) biomass at pH 3.0, 4.0, and 4.5, respectively. Results from desorption studies, SEM (scanning electron microscopy), TEM (transmission electron microscopy), and EDX (energy-dispersive X-ray spectroscope) analyses confirmed that surface complexation was the main process involved in Cr(III) biosorption. Potentiometric titration revealed that carboxyl (pKa1 = 4.10), phosphonate (pKa2 = 6.36) and amine (pKa3 = 8.47) functional groups on the surface of Chlorella miniata were the possible sites for Cr uptake, and their average amounts were 0.53, 0.39, and 0.36 mmol g(-1) biomass, respectively. A surface complexation model further indicated that carboxyl group played the main role in Cr(III) complexation, with a binding constant of K11 = 1.87 x 10(-4) and K12 = 6.11 x 10(-4) for Cr3+ and Cr(OH)2+, respectively. This model also suggested that the hydroxy species was more easily to complex with the cell surface of Chlorella miniata.     

Electron capture dissociation of peptides metalated with alkaline-earth metal ions

The possible use of divalent alkaline-earth metal ions, including Mg2+, Ca2+, Sr2+, and Ba2+, as charge carrier for electron capture dissociation of peptides was investigated. Model peptides of RGGGVGGGR and NGGGWGGGN were used to simplify the interpretation of spectral information. It was demonstrated that useful electron capture dissociation (ECD) tandem mass spectra of these metalated peptides could be generated. Interestingly, peptides metalated with different alkaline-earth metal ions generated very similar ECD tandem mass spectra. Metalated c-ions and z-ions were the predominant fragment ions. Only Mg2+-metalated peptides gave somewhat different results. Some nonmetalated c-ions were observed from ECD of [RGGGVGGGR + Mg]2+ but not from [NGGGWGGGN + Mg]2+. Together with some ab initio calculations, it was established that the bound metal ions might activate the acidity of the amide hydrogen. With the presence of high proton affinity moiety, such as N-terminal amino group and/or side chain of the arginine residues, the metalated peptide ions could exist predominantly in their zwitterion forms, in which one or two backbone amide group(s) was deprotonated and the high proton affinity functional group(s) was protonated. It was believed that electron capture leads primarily to the reduction of the mobile proton rather than the metal ions. With this zwitterion model, the formation of nonmetalated c-fragments and the generation of similar ECD spectra for peptides metalated with various alkaline-earth metal ions could readily to be explained. Another interesting observation in the ECD mass spectra of metalated peptides is related to the enhanced formation of the minor ECD products, i.e., (c - 1)(+*) and (z + 1)+ ions. Together with ab initio calculations using a truncated peptide model, various possible reaction mechanisms for the formation of these minor ECD products were evaluated. It was concluded that hydrogen transfer between the initiated formed c and z(.) species plays an important role in the formation (c - 1)(+*) and (z + 1)+ ions. Although peptides metalated with these metal ions do not have better ECD efficiency compared to the multiply-protonated peptides, it provides practical accessibility of ECD methods to analyze small peptides with no basic amino acid residues.     

Performance of a slow positron beam using a hybrid lens design

The University of Hong Kong positron beam employs conventional magnetic field transport to the target, but has a special hybrid lens design around the positron moderator that allows the beam to be focused to millimeter spot sizes at the target. The good focusing capabilities of the beam are made possible by extracting work-function positrons from the moderator in a magnetic field free region using a conventional Soa lens thus minimizing beam canonical angular momentum. An Einzel lens is used to focus the positrons into the magnetic funnel at the end of transportation magnetic field while at the same time bringing up the beam energy to the intermediate value of 7.5 keV. The beam is E × B filtered at this intermediate energy. The final beam energy is obtained by floating the Soa-Einzel system, E × B filter and flight tube, and accelerating the positrons just before the target. External beam steering saddle coils fine tune the position, and the magnetic field around the target chamber is adjusted so as to keep one of the beam foci always on the target. The system is fully computer controlled. Variable energy-Doppler broadened annihilation radiation (VEDBAR) data for a GaN sample are shown which demonstrate the performance of the positron beam system.