Development of a hypoxia-selective near-infrared fluorescent probe for non-invasive tumor imaging

A near-infrared fluorochrome, GPU-311, was designed, synthesized and evaluated for its application in non-invasive imaging of tumor hypoxia. Efficient synthesis was achieved by nucleophilic substitution and click chemistry ring using the bifunctional tetraethylene glycol linker 2 containing thiol and azide groups for the conjugation of the propargylated nitroimidazole 1 and the heptamethine cyanine dye 3 bearing a 2-chloro-1-cyclohexenyl ring. GPU-311 exhibited long excitation and emission wavelength (Ex/Em=785/802?nm) and a decent quantum yield (0.05). The water solubility and hydrophilicity of GPU-311 increased. After in vitro treatment of SUIT-2/HRE-Luc pancreatic cancer cells with GPU-311, a higher level of fluorescence was observed selectively in hypoxia than in normoxia. However, in vivo fluorescence imaging of a mouse xenograft model after GPU-311 administration revealed inadequate accumulation of GPU-311 in tumors due to its rapid elimination through the liver.     

System of mobile agents to model social networks

We propose a model of mobile agents to construct social networks, based on a system of moving particles by keeping track of the collisions during their permanence in the system. We reproduce not only the degree distribution, clustering coefficient, and shortest path length of a large database of empirical friendship networks recently collected, but also some features related with their community structure. The model is completely characterized by the collision rate, and above a critical collision rate we find the emergence of a giant cluster in the universality class of two-dimensional percolation. Moreover, we propose possible schemes to reproduce other networks of particular social contacts, namely, sexual contacts.     

Calculated ultraviolet exposure levels for a healthy vitamin D status

The dangers of overexposure to sunlight have been well publicized, but less attention has been given to an acknowledged benefit of exposure to UV radiation; that being the cutaneous synthesis of vitamin D3. Here we define a standard vitamin D dose on the basis of recently recommended requirements for vitamin D that take account of its risk reduction role in a variety of diseases, and present a web-based tool that enables the reader to calculate associated exposure times for any time and place using either default values or user-selected conditions. Either it is not possible to synthesize vitamin D3 at high latitudes in winter, or the exposure time required to reach a standard dose is sometimes impractical. Where solar UV is sufficient, a risk-benefit analysis of sunburn vs. vitamin D3 synthesis shows that the best time for brief sun exposure is in the middle of the day. For low solar elevation angles common at high latitudes, a fine line exists between adequate UV exposure for vitamin D3 synthesis and a risk of sun burn.     

Regioselectivity in aqueous palladium catalysed hydroxycarbonylation of styrene: a catalytic and mechanistic study

Regioselectivity control was studied in palladium catalysed hydroxycarbonylation of styrene in neat water with water-soluble phosphines, mostly trisulfonated triphenylphosphine, TPPTS, but also N-bis(N',N'-diethyl-2-aminoethyl)-4-aminomethylphenyl-diphenylphosphine, N3P. The factor giving the highest changes in regioselectivity in the TPPTS system, under similar reaction conditions, is the temperature. In the N3P case, only a minor variation in the n/i ratio as a function of temperature is observed. Insitu normal- and high-pressure NMR experiments were performed to obtain further information about the catalytic cycle and the reaction intermediates. Two palladium hydride intermediates, a palladium eta3-benzylic complex and both the branched and linear palladium acyl complexes were identified in the HP NMR experiments. The hydroxycarbonylation in water using styrene as a substrate operates using a hydride mechanism for pathways leading to both linear and branched product. Insertion of styrene in the palladium-hydride bond gives an eta3-benzyl compound. A high CO pressure gives a kinetic preference for the iso-acyl in the next step. In the TPPTS system, at moderate temperatures, the hydrolysis of the iso-acyl is faster than its conversion to the thermodynamically more stable n-acyl. A low n/i therefore requires high pressures and reasonably low temperatures. The N3P ligand always favours the linear product since isomerisation of the iso-acyl to the n-acyl in this system is fast under all conditions investigated.     

A database-centric virtual chemistry system

We describe an Oracle database application for general use within virtual chemistry. The application functions as a central hub and repository for chemical data with interfaces to external calculators. It deals with the general problems of merging data from disparate sources and with scheduling of computational tasks for parallel or sequential execution in a mixed environment. The central database is used for the storage of input, intermediary, and final data as well as for job control. A calculation job is split into distinct tasks, or units of work, which are put in a queue. Tasks are dequeued and handled by specialized calculators. These calculators are in-house or commercial programs for which adaptor modules for connection to the database must be written. Tasks are handled in a transactional fashion, so that uncompleted or failed tasks are left in the queue. This makes the system stable to many types of disturbances. Sorting, filtering, and merging operations are handled by the database itself. Usage is very general, but some specific examples are (1) as a back end for a chemical property calculator Web page, (2) in an automated quantitative structure-activity relationship system, and (3) in virtual screens.     

Kinetic effects of hydrogen bonds on proton-coupled electron transfer from phenols

The kinetics and mechanism of proton-coupled electron transfer (PCET) from a series of phenols to a laser flash generated [Ru(bpy)(3)](3+) oxidant in aqueous solution was investigated. The reaction followed a concerted electron-proton transfer mechanism (CEP), both for the substituted phenols with an intramolecular hydrogen bond to a carboxylate group and for those where the proton was directly transferred to water. Without internal hydrogen bonds the concerted mechanism gave a characteristic pH-dependent rate for the phenol form that followed a Marcus free energy dependence, first reported for an intramolecular PCET in Sj?din, M. et al. J. Am. Chem. Soc. 2000, 122, 3932-3962 and now demonstrated also for a bimolecular oxidation of unsubstituted phenol. With internal hydrogen bonds instead, the rate was no longer pH-dependent, because the proton was transferred to the carboxylate base. The results suggest that while a concerted reaction has a relatively high reorganization energy (lambda), this may be significantly reduced by the hydrogen bonds, allowing for a lower barrier reaction path. It is further suggested that this is a general mechanism by which proton-coupled electron transfer in radical enzymes and model complexes may be promoted by hydrogen bonding. This is different from, and possibly in addition to, the generally suggested effect of hydrogen bonds on PCET in enhancing the proton vibrational wave function overlap between the reactant and donor states. In addition we demonstrate how the mechanism for phenol oxidation changes from a stepwise electron transfer-proton transfer with a stronger oxidant to a CEP with a weaker oxidant, for the same series of phenols. The hydrogen bonded CEP reaction may thus allow for a low energy barrier path that can operate efficiently at low driving forces, which is ideal for PCET reactions in biological systems.     

Amino-functionalization of large-pore mesoscopically ordered silica by a one-step hyperbranching polymerization of a surface-grown polyethyleneimine

A simple method for surface functionalization of large-pore mesoporous silica by hyperbranching polymerization resulting in a high loading of amine groups is presented.     

Efficient and selective sulfoxidation by hydrogen peroxide, using a recyclable flavin--[BMIm]PF6 catalytic system

A new flavin catalyst 2 immobilized in an ionic liquid ([BMIm]PF6) was used for the highly selective oxidation of sulfides to sulfoxides by hydrogen peroxide. The sulfoxides were obtained in good to high yields and high selectivity without any detectable overoxidation to sulfone. The catalyst in the ionic liquid was recycled up to seven times without loss of activity or selectivity.     

A Generalization of a Levitin and Parnovski Universal Inequality for Eigenvalues

In this paper, we derive “universal” inequalities for the sums of eigenvalues of the Hodge de Rham Laplacian on Euclidean closed submanifolds and of eigenvalues of the Kohn Laplacian on the Heisenberg group. These inequalities generalize the Levitin–Parnovski inequality obtained for the sums of eigenvalues of the Dirichlet Laplacian of a bounded Euclidean domain.