Boronated protohaemins: synthesis and in vivo antitumour efficacy

The conjugates of porphyrin macrocycles with boron-containing polyhedra are under investigation as agents for binary treatment strategies of cancer. Aiming at the design of photoactive compounds with low-to-zero dark toxicity, we synthesized a series of carboranyl and monocarbon-carboranyl derivatives of protohaemin IX using the activation of porphyrin carboxylic groups with di-tert-butyl pyrocarbonate or pivaloyl chloride. The water-soluble 1,3,5,8-tetramethyl-2,4-divinyl-6(7)-[2'-(closo-monocarbon-carborane-1'-yl)methoxycarbonylethyl]-7(6)-(2'-carboxyethyl)porphyrin Fe(III) (compound 9) exerted no discernible cytotoxicity for cultured mammalian cells, nor did it cause general toxicity in rats. Importantly, 9 demonstrated dose-dependent activity as a phototoxin in photodynamic therapy of M-1 sarcoma-bearing rats. In animals injected with 20 mg kg(-1) of 9, the tumours shrank by day 3 after one single irradiation of the tumour with red laser light. Between 7 and 14 days post-irradiation, 88.9% of rats were tumour-free; no recurrence of the disease was detectable within at least 90 days. Protohaemin IX alone was without effect, indicating that boronation is important for the phototoxic activity of 9. This is the first study that presents the synthesis and preclinical in vivo efficacy of boronated derivatives of protohaemin as phototoxins. The applicability in photodynamic treatment broadens the therapeutic potential of boronated porphyrins beyond their conventional role as radiosensitizers in boron neutron capture therapy.     

Structure of Ir and Ir-Al<Subscript>2</Subscript>o<Subscript>3</Subscript> coatings obtained by chemical vapor deposition in the presence of oxygen

By chemical vapor deposition Ir and Ir-Al₂O₃ coatings are obtained with a thickness of up to 40 fum on steel substrates precoated with a layer of Al₂O₃. Tris-acetylacetonates of iridium(III) and aluminium(III) are used as precursors. The deposition processes are carried out at atmospheric pressure in the presence of oxygen. The obtained coatings are studied by X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The dependences of coating structures and compositions on the preparation conditions are found. An increase in the deposition temperature results in the formation of Ir coatings with loose discontinuous structure, an increase in the size of metal crystallites, and the growth of the oxygen concentration in their composition. An increase in the concentration of precursor vapors in the deposition zone at a constant deposition temperature results in the formation of Ir coatings that consist of differently structured layers (compact, columnar, and granular). Mixed Ir-Al₂O₃ coatings which composed of metal Ir and amorphous Al₂O₃ crystallites, which exhibit a pronounced iridium texture in the [111] direction, have the most perfect compact structure. The introduction of the oxide phase in the coating composition halves the Ir crystallite size.     

On a family of nonlocal difference schemes

We consider a weighted difference scheme approximating the heat equation with nonlocal boundary conditions. We analyze the behavior of the spectrum of the main finite-difference operator depending on the parameters occurring in the boundary conditions. We state inequalities whose validity is necessary and sufficient for the stability of the difference scheme with respect to the initial data.     

An investigation into the sensitivity of various albedo neutron dosimeters aimed at correcting the readings

The results of an experimental determination of the sensitivity of three types of individual neutron albedo dosimeters in neutron reference fields on the basis of radionuclide sources and at the top concrete shielding of the U-70 accelerator are presented. The results show that the ratios between the responses of the albedo dosimeters designed earlier at the Joint Institute for Nuclear Research (the albedo dosimeter (AD) and the multicomponent dosimeter (MD)) and the currently used DVGN-01 dosimeter are constant within 25% in a wide range of neutron energy. This fact makes it possible to use the results of measuring the AD and MD responses obtained earlier in neutron fields of nuclear-physical installations at the Joint Institute for Nuclear Research (JINR) for the correction of DVGN-01 dosimeter measurement results to apply it to personal radiation monitoring (PRM) at these installations. The correction factors for DVGN-01 measurement results are found and recommended to be used in PRM for most JINR installations.