Water-soluble quaternized mercaptopyridine-substituted zinc-phthalocyanines: Synthesis, photophysical, photochemical and bovine serum albumin binding properties

The synthesis and characterization of the new zinc phthalocyanine derivatives, tetra- (non-peripheral, 5) and octa-(peripheral, 6) substituted with 2-mercaptopyridine and their respective quaternized derivatives (8 and 9) are reported. Photochemical and photophysical properties of the new complexes are compared with those of the previously reported peripherally tetra-substituted complexes 7 and 10. The quaternized compounds exhibit excellent solubility in water, making them potential photosensitizers for use in photodynamic therapy (PDT) of cancer. Spectroscopic, aggregation, photophysical and photochemical properties of these complexes are also investigated and compared. Photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yield) properties of these phthalocyanine photosensitizers are very important for the assessment of these complexes as PDT agents. In this study, the effects of the position of the substituents and quaternization of the substituents on the photophysical and photochemical parameters of the zinc phthalocyanines are also reported. This study also showed that the water-soluble quaternized zinc phthalocyanines strongly bind to blood plasma proteins such as bovine serum albumin (BSA).     

On the analysis of a dynamical model representing gene regulatory networks under negative feedback

In this work, stability analysis is performed for a cyclic dynamical model of gene regulatory networks involving time delays, under negative feedback. The model considered has nonlinearities with negative Schwarzian derivatives. Sufficient conditions implying global stability of these types of GRNs are obtained. The special case of homogenous gene regulatory networks is also studied; in this case, the proposed stability conditions depend only on the parameters of the nonlinearity function. Illustrative numerical examples complete the presentation.Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of interactions with the surface on the orientation of the mesogenic monoazacrown-substituted phthalocyanine films

In this paper, the effect of interaction with the substrate surface on the orientation of films' molecules of substituted liquid crystalline phthalocyanines M(II)Pc (M = Cu, Ni, Zn) having monoazacrown ether moieties on the periphery containing long alkyloxyphenyl N-pivotal groups is studied. The phthalocyanine derivatives demonstrate thermotropic mesophase behaviour and show Col_h mesophases over a wide temperature range. The preferential orientation of the phthalocyanine films deposited on glass, silicon and NaCl substrates as well as between two of those substrates is studied by polarized Raman spectroscopy at different temperatures. These phthalocyanines form homeotropically aligned films on the surface of NaCl substrate, whereas planar alignment with a random distribution of the column directors occurs on the glass slides.     

Comparison of photophysicochemical properties of hexaphenoxycyclotriphosphazenyl-substituted metal-free,mono- and bis-lutetium phthalocyanines

The aim of this study is to compare the photophysicochemical properties of hexaphenoxycyclotriphosphazenyl-substituted metal-free (1), mono-(phthalocyaninato) lutetium(III) (2) [Lu^III(AcO)(Pc)] (Pc = phthalocyaninato, AcO = acetate) and bis-(phthalocyaninato) lutetium(III) (3) [Lu^IIIPc₂]. The synthesis and characterization (using the elemental analysis, mass spectrometry, IR, ¹H, and ³¹P NMR and UV–vis spectroscopy) of new compounds (2, 3) are described in this study. The electronic absorption and fluorescence spectral properties of compounds 1–3 are investigated. Photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yields) measurements are also studied on hexaphenoxycyclotriphosphazenyl-appended metal-free, mono- and bis-lutetium phthalocyanines in dimethylsulfoxide (DMSO). Photophysical and photochemical properties of phthalocyanines are very useful for photodynamic therapy (PDT) applications. Singlet oxygen quantum yields (Φ_Δ) give an indication of the potential of the complexes as photosensitizers in PDT applications. Hexaphenoxycyclotriphosphazenyl-substituted mono-(phthalocyaninato) lutetium(III) complex (2) gave good singlet oxygen quantum yield (0.66) in DMSO. Thus, this complex shows potential as Type II photosensitizer for PDT of cancer.     

High-throughput screening for kinase inhibitors

Following G protein-coupled receptors (GPCRs), protein kinases have become the second most important class of targets for drug discovery over the last 20 years. While only four kinase inhibitors have reached the market to date (Fasudil for rho-dependent kinase, Rapamycin for TOR, Gleevec for BCR-Abl, and Iressa for EGFR), many more are already in clinical development. A historical overview of kinase inhibitors was recently published by Cohen. [1] After the previous successes, protein kinases are now regarded as attractive, well-drugable targets, and the analysis of the human genome has yielded 518 protein kinases. [2] We can thus expect screening for protein kinase inhibitors to become even more important in the future. In this review we will focus on the early steps of drug discovery programs producing new lead compounds. We will guide the reader through efficient state-of-the-art assay development and high-throughput screening of large chemical libraries for protein kinase inhibitors.     

Tuning pH sensitivities of zinc phthalocyanines in ionic liquid modified matrices

Phthalocyanine dyes are clinically important bright fluorophores with many desirable properties. Their absorption and emission maxima in near infrared region make them proper tool for optical probing of biologically relevant materials and optical-chemical-sensing purposes. In this work we have shown that pH sensitivities of the phthalocyanines can be manipulated as desired. This property makes the Pcs very proper photosensitizers for photodynamic therapy applications. In this work pH sensitivities of alpha (α) and beta (β) tetra-substituted zinc phthalocyanines (ZnPcs) were studied spectroscopically in ethyl cellulose and PVC matrices. In experiments designed to manipulate pH, lipophilic room temperature ionic liquids (RTILs) were added into the test environment. The RTIL-modified thin films provided higher relative fluorescence intensity changes upon exposure to proton with respect to the RTIL-free ones. By this way, acidity constants of the ZnPcs could be tuned to the desired region of interest. The ZnPcs, exhibited good reproducibility and reversibility upon protonation. The RTILs also enhanced short and long term stabilities of the Pc-dyes. There was no significant drift in their proton sensitivities even after 10 assays and after being stored in a buffer condition for over six months.     

Identification of specific Rp-phosphate oxygens in the tRNA anticodon loop required for ribosomal P-site binding

tRNA binding to the ribosomal P site is dependent not only on correct codon-anticodon interaction but also involves identification of structural elements of tRNA by the ribosome. By using a phosphorothioate substitution-interference approach, we identified specific nonbridging Rp-phosphate oxygens in the anticodon loop of tRNA(Phe) from Escherichia coli which are required for P-site binding. Stereospecific involvement of phosphate oxygens at these positions was confirmed by using synthetic anticodon arm analogues at which single Rp- or Sp-phosphorothioates were incorporated. Identical interference results with yeast tRNA(Phe) and E. coli tRNA(fMet) indicate a common backbone conformation or common recognition elements in the anticodon loop of tRNAs. N-ethyl-N-nitrosourea modification-interference experiments with natural tRNAs point to the importance of the same phosphates in the loop. Guided by the crystal structure of tRNA(Phe), we propose that specific Rp-phosphate oxygens are required for anticodon loop ("U-turn") stabilization or are involved in interactions with the ribosome on correct tRNA-mRNA complex formation.