Novel methyl helianthrones as photosensitizers: synthesis and biological evaluation

A combination of light, oxygen and a photosensitizer is used to induce death of cancer cells by photodynamic therapy. In this study, we have synthesized several new methyl helianthrone derivatives and compared their phototoxicity with that of hypericin. In contrast to hypericin, methyl helianthrones are soluble in aqueous solutions and have a broad range of light absorbance, which allows the use of polychromatic light. Structural modifications of methyl helianthrone demonstrated that substitution of hydrogen atoms of methyl helianthrone at Positions 2 and 5 with Br atoms or methylation of its phenolic hydroxyls, significantly increases the corresponding singlet oxygen quantum yield and their phototoxicity toward alphaT3-1, M2R and LNCaP cells. The phototoxicity of some of these compounds was similar to that of hypericin. Methyl helianthrones, like hypericin, accumulated mainly in the perinuclear region as evident by confocal microscopy. Irradiation of cells pretreated with methyl helianthrone derivatives generates intracellular reactive oxygen species and lipid free radicals, as shown by a fluorescentic probe and electron paramagnetic resonance methods, respectively. The phototoxicity of these methyl helianthrones as well as their ability to oxidize membrane lipids were significantly decreased on addition of specific Type-II inhibitors, suggesting the involvement of singlet oxygen as the main oxidant.     

The two-cardinals transfer property and resurrection of supercompactness

We show that the transfer property for singular does not imply (even) the existence of a non-reflecting stationary subset of . The result assumes the consistency of ZFC with the existence of infinitely many supercompact cardinals. We employ a technique of ``resurrection of supercompactness'. Our forcing extension destroys the supercompactness of some cardinals; to show that in the extended model they still carry some of their compactness properties (such as reflection of stationary sets), we show that their supercompactness can be resurrected via a tame forcing extension.

     

Ligand binding and unfolding of tryptophan synthase revealed by ion mobility-tandem mass spectrometry employing collision and surface induced dissociation

Understanding protein tertiary and quaternary structures is crucial to a better understanding of their biological functions. Here we illustrate for tryptophan synthase that tandem mass spectrometry (MS/MS) reveals not only protein subunit architectures, but also protein unfolding behavior when coupled with ion mobility (IM). In the present study, we verified the subunit arrangement with surface induced dissociation (SID). We are able to correlate experimental results by IM with those obtained in unfolding simulations for the hetero-tetramer Tryptophan Synthase (TS) protein complex by identifying the presence of at least three stable intermediates (I₁, I₂, and I₃) during the unfolding process in collision induced dissociation (CID). We illustrate that the unfolding of the TS complex is likely due to the initial unfolding of an α-monomer subunit, followed by the unfolding of the second α-monomers. We also illustrate the ability of this combination of techniques to not only identify conformational changes of TS upon addition of D,L-α-glycerol phosphate (GP), but also to determine the location of the ligand, which is buried within the α-monomer of the TS.     

Limited path percolation in complex networks

We study the stability of network communication after removal of a fraction q=1-p of links under the assumption that communication is effective only if the shortest path between nodes i and j after removal is shorter than al(ij)(a> or =1) where l(ij) is the shortest path before removal. For a large class of networks, we find analytically and numerically a new percolation transition at p(c)=(kappa(0)-1)((1-a)/a), where kappa(0) [triple bond] / and k is the node degree. Above p(c), order N nodes can communicate within the limited path length al(ij), while below p(c), N(delta) (delta<1) nodes can communicate. We expect our results to influence network design, routing algorithms, and immunization strategies, where short paths are most relevant.     

Current development of analytical affinity chromatography: Design and biotechnological uses of molecular recognition surfaces

Analytical high performance liquid affinity chromatography (analytical HPLAC) has been investigated as an experimental guide to both synthetic design and affinity technological use of peptide and protein recognition surfaces. This work has progressed from the ongoing use of analytical affinity chromatography to study interaction mechanisms of naturally-occurring peptides and proteins, including enzyme fragment complexes and neuroendocrine biosynthetic precursors. We recently initiated a study to use analytical HPLAC for de novo design of recognition peptides called “anti-sense peptides”. Present data suggest the potential to use anti-sense peptides as “synthetic antibodies”, in immobilized forms, for biomolecular separation and analysis. Analogous studies have been started with immobilized natural antibodies in analytical immuno HPLAC. Our present data typify the growing usefulness of analytical HPLAC when designing recognition molecules, analyzing their interaction characteristics, and devising ways to use them in affinity technology.     

Tunneling into the normal state of Pr2-xCexCuO4

The temperature dependence of the tunneling conductance was measured for various doping levels of Pr(2-x)CexCuO4 using planar junctions. A normal state gap is seen at all doping levels studied, x=0.11 to x=0.19. We find it to vanish above a certain temperature T*. T* is greater than T(c) for the underdoped region and it follows T(c) on the overdoped side. This behavior suggests finite pairing amplitude above T(c) on the underdoped side.     

Regular characters of classical groups over complete discrete valuation rings

Let $\mathfrak{o}$ be a complete discrete valuation ring with finite residue field $\mathsf{k}$ of odd characteristic, and let G be a symplectic or special orthogonal group scheme over $\mathfrak{o}$. For any $?\in \mathbb{N}$ let $G^{?}$ denote the ?-th principal congruence subgroup of $\mathbf{G}(\mathfrak{o})$. An irreducible character of the group $\mathbf{G}(\mathfrak{o})$ is said to be regular if it is trivial on a subgroup $G^{?+1}$ for some ?, and if its restriction to $G^{?}/G^{?+1}?\mathrm{Lie}(\mathbf{G})(\mathsf{k})$ consists of characters of minimal $\mathbf{G}({\mathsf{k}}^{\mathrm{alg}})$-stabilizer dimension. In the present paper we consider the regular characters of such classical groups over $\mathfrak{o}$, and construct and enumerate all regular characters of $\mathbf{G}(\mathfrak{o})$, when the characteristic of $\mathsf{k}$ is greater than two. As a result, we compute the regular part of their representation zeta function.     

Morphology and photocatalytic activity of TiO2 Aerogels

In this paper we describe a methodology to form a data base that will allow us to investigate the correlation between the morphology of Ti?₂ aerogels and their photocatalytic activity with respect to photodecomposition of a water soluble organic compound. We start with a qualitative theoretical argument in which we show that any functionality that involves optimization of different length scale should require some kind of ramified structure. For photocatalytic activity we need to optimize substrate and light absorptions with diffusion of products and reactants. We proceed to describe the techniques that we use to analyze and parametrize the morphology of the aerogels, using nitrogen adsorption and Small Angle Neutron Scattering. The photocatalytic activity is monitored through the photodecomposition of salicylic acid. We compare the adsorption and photodegradation of salicylic acid on the aerogels to many other forms of TiO₂ and report that under our experimental conditions the photocatalytic activity of the aerogels is superior.     

PHOTOREGULATION OF α-CHYMOTRYPSIN ACTIVITY IN ORGANIC MEDIA: EFFECTS OF BIOIMPRINTING

Abstract α-Chymotrypsin exhibits photoswitchable activities in an organic solvent after covalent modification of the protein backbone with thiophenefulgide active ester (2). The thiophenefulgide-modified α-chymotrypsin exhibits reversible photoisomerizable properties between states (3)-E and (3)-C. The modified α-chymotrypsin, where nine lysine residues are substituted by thiophenefulgide units, retains 60% of the activity of the native enzyme. The activities of thiophenefulgide-modified α-chymotrypsin toward esterification of N -acetyl-L-phenylalanine (4) by ethanol in cyclohexane are controlled by the configuration of the attached photoisomerizable component and by prior bioimprinting of the protein backbone with the reaction substrate (4). The esterification of (4) in cyclohexane using bioimprinted (3)-C is two-fold faster than in the presence of (3)-E. In the presence of a nonbioimprinted enzyme, esterification of (4) by (3)-C is five-fold faster than with (3)-E. The activity of bioimprinted (3)-E toward esterification of (4) is 4.5-fold higher than that of nonbioimprinted (3)-E. Switchable cyclic esterification of (4) is accomplished by sequential photoisomerization of the thiophenefulgide-modified α-chymotrypsin between states (3)-C and (3)-E.