Estimation and correction of Cerenkov-light on luminescence image of water for carbon-ion therapy dosimetry

PurposeThe luminescence images of water during the irradiation of carbon-ions provide useful information such as the ranges and the widths of carbon-ion beams. However, measured luminescence images show higher intensities in shallow depths and wider lateral profiles than those of the dose distributions. These differences prevent the luminescence imaging of water from being applied to a quality assurance for carbon-ion therapy. We assumed that the differences were due to the contaminations of Cerenkov-light from the secondary electrons of carbon-ions as well as the prompt gamma photons in the measured image. In this study, we applied a correction method to a luminescence image of water during the irradiation of carbon-ion beams.MethodsWe estimated the distribution of the Cerenkov-light in water during the irradiation of carbon-ions by Monte Carlo simulation and subtracted the simulated Cerenkov-light from the depth and lateral profiles of the measured luminescence image for 241.5 MeV/u-carbon-ions.ResultsWith these corrections, we successfully obtained depth and lateral profiles whose distributions are almost identical to the dose distributions of carbon-ions. The high intensities in the shallow depth areas decreased and the Bragg peak intensity increased. The beam widths of the measured images approached those of the ionization chamber.ConclusionsThese results indicate that the luminescence imaging of water with our proposed correction has potential to be used for dose distribution measurements for carbon-ion therapy dosimetry.     

Design,synthesis and evaluation of carbamate-linked uridyl-based inhibitors of human ST6Gal I

Sialic acid at the terminus of cell surface glycoconjugates is a critical element in cell-cell recognition, receptor binding and immune responses. Sialyltransferases (ST), the enzymes responsible for the biosynthesis of sialylated glycans are highly upregulated in cancer and the resulting hypersialylation of the tumour cell surface correlates strongly with tumour growth, metastasis and drug resistance. Inhibitors of human STs, in particular human ST6Gal I, are thus expected to be valuable chemical tools for the discovery of novel anticancer drugs. Herein, we report on the computationally-guided design and development of uridine-based inhibitors that replace the charged phosphodiester linker of known ST inhibitors with a neutral carbamate to improve pharmacokinetic properties and synthetic accessibility. A series of 24 carbamate-linked uridyl-based compounds were synthesised by coupling aryl and hetaryl α-hydroxyphosphonates with a 5′-amino-5′-deoxyuridine fragment. The inhibitory activities of the newly synthesised compounds against recombinant human ST6Gal I were determined using a luminescent microplate assay, and five promising inhibitors with K_i’s ranging from 1 to 20 µM were identified. These results show that carbamate-linked uridyl-based compounds are a potential new class of readily accessible, non-cytotoxic ST inhibitors to be further explored.     

Two cadmium-thiocyanate coordination polymers with organic cations: Synthesis, crystal structures and luminescent properties

Two new inorganic-organic hybrid polymers [ClBzQl]₂[Cd(SCN)_3.5Br_0.5]·0.25H₂O (1) and [ClBzMePy][Cd(SCN)₃] (2) (ClBzQl = 1-(4′-Cl-benzyl)quinolinium cation and ClBzMePy = 1-(4′-Cl-benzyl)-2-methylpyridinium cation) have been synthesized and characterized by IR, UV, elemental analysis and X-ray crystallography. Crystal structure analyses show that two polymers belong to the monoclinic space group P2/n (1) and P2₁/c (2) with a = 18.548(2) Å, b = 9.526(1) Å, c = 20.689(2) Å, β = 94.008(1)°, V = 3646.6(5) Å³ for 1, and a = 11.195(2) Å, b = 16.415(3) Å, c = 10.751(2) Å, β = 102.930(3)°, V = 1925.7(7) Å³ for 2. The Cd atom exhibits a distorted octahedral coordination geometry for 1 and 2. For 1, a pair of 1,1-μ-SCN⁻ anions and a pair of 1,3-μ-SCN⁻ anions are alternately bridge adjacent Cd centers to form infinite polymeric chains. For 2, adjacent Cd atoms are linked by three 1,3-μ-SCN⁻ anions to form infinite [Cd(SCN)₃⁻]_∞ polymeric chains. The luminescent properties of the two polymers in the solid state at room temperature were investigated.     

Spectroscopic, cytotoxic and DFT studies of a luminescent palladium(II) complex of a hydrazone ligand that induces apoptosis in human prostate cancer cells

A luminescent palladium(II) complex [Pd(L)Cl], 1a was synthesized with the acyclic tridentate quinoline-2-carboxaldehyde-2-pyridylhydrazone ligand, HL, 1. The ligand, 1 showed a selective chromogenic behavior towards Pd²⁺ by changing the color of the solution from yellow to blue-violet, which can easily be detected by the naked-eye. DFT and TDDFT calculations were performed to determine the geometry optimized structures of the ligand 1 and the complex 1a as well as to correlate the electronic transitions. The complex 1a exhibits strong interaction towards DNA as revealed from K_b (intrinsic binding constant) and K_sq (Stern Volmer quenching constant) values, which are 1.47 × 10⁵ M⁻¹ and 5.67, respectively. The cytotoxicity of 1a has been examined with human prostate cancer cells (PC-3) and the sub-lethal dose (8 μM) determined by dose-dependence studies. The relative degree of apoptotic and necrotic cell death using a sub-lethal dose were measured by flow cytometry. The cell cycle analysis shows that the complex 1a exhibits effective cell growth inhibition by triggering G2/M phase arrest and apoptosis in cancer cells. Moreover, its treatment triggers the mitochondrial pathway resulting in cytochrome c release and caspase-3 activation.     

A novel type of copper(I)/(II) mixed-valence compound: [Cu(dmp)2][Cu(hfac)3] with dmp=2,9-dimethyl-1,10-phenanthroline and hfac=hexafluoroacetylacetonate

The mixed-valence compound [Cu^I(dmp)₂][Cu^II(hfac)₃] with dmp=2,9-dimethyl-1,10-phenanthroline and hfac⁻=hexafluoroacetylacetonate has been synthesized and structurally characterized by X-ray crystallography. The MV interaction has been examined by emission spectroscopy. The phosphorescence of [Cu^I(dmp)₂]⁺ is completely quenched. It is suggested that this quenching takes place by excited state electron transfer from Cu(I) to Cu(II).     

Metal-metal stacking patterns between and with [Pt(tpy)X] cations

A comparative study of metallophilic interactions of [Pt(tpy)X]⁺ cations (tpy = 2,2′:6′,2″-terpyridine) in the presence of two different types of anions, (i) []⁻ anions that form double salts and (ii) simple p-block anions, is reported. Single-crystal X-ray diffraction data, solution-state ¹⁹⁵Pt NMR spectra, and variable temperature solid-state luminescence spectra are reported. Three [Pt(tpy)Cl]Y derivatives (Y = SbF₆, 1, SbF₆·CH₃CN, 4, PF₆, 2) and the [Pt(tpy)Br]PF₆ analog, 3, as well as two new double salts [Pt(tpy)CN][Au(CN)₂], 5, and [Pt(tpy)CN]₂[Au(C₆F₅)₂](PF₆), 6, have been synthesized and characterized. Structural analysis shows consistent patterns in Pt···Pt interactions that vary slightly depending on the coordinating halogen or pseudo-halogen X, counter anion Y, and lattice solvent. Metallophilic interactions are seen between [Pt(tpy)X]⁺ cations with all types of X ligands, but only with π-accepting X′ ligands from []⁻ anions are Pt?Au metallophilic interactions seen to be favored over Pt?Pt interactions. The [Au(CN)₂]⁻ anion consistently forms Pt···Au metallophilic contacts, unlike [Au(C₆F₅)₂]⁻. The ¹⁹⁵Pt NMR chemical shifts are ∼−2750 ppm for π-donor ligands and near −3120 ppm for π-acceptor ligands in [Pt(tpy)X]PF₆ compounds. Luminescence data show an unusual blue shift in [Pt(tpy)CCPh][Au(C₆F₅)₂] versus [Pt(tpy)CCPh]PF₆ ascribed to an intermolecular charge transfer.     

Synthesis, characterization, crystal structure and luminescence properties of phosphinic silver(I) complexes with thiourea derivatives

Reaction of phenylisothiocyanate with different aromatic amines allowed the synthesis of compounds containing the thiourea moiety. By reacting silver bis(triphenylphosphine)nitrate with suitable ligands belonging to this family of sulphurated compounds, three new complexes have been afforded. Ligands and complexes were characterized also by X-ray diffraction. The structures reveal remarkable differences in the silver coordination geometry in function of the nature and size of the ligand. The emission properties of all compounds were characterized at 10 and at 298 K.     

AT-dependent luminescence of DNA-threading ruthenium complexes

Whereas the emission from the ruthenium complex deltadelta-[mu-bidppz(phen)4Ru2]4+ (P) is five times larger when intercalated into poly(dAdT)2 than when intercalated into ct-DNA, the homologue deltadelta-[mu-bidppz(bipy)4Ru2]4+ (B) has a smaller quantum yield and a red-shifted emission. The origin of this difference is here investigated by studying intercalation into oligonucleotides containing a central AT-tract. Increasing the length of the AT-tract increases the emission quantum yield for P but decreases it for B. However, not even four helix turns of AT base pairs is enough to mimic poly(dAdT)2. B and P thus use the increased flexibility with increasing length of the AT-tract in opposite ways, whereas B gets more prone to quenching by water, P gets more protected from quenching. The earlier reported gradual increase of the intercalation rate with AT-stretch length is thus paralleled by a gradual change in the equilibrium properties of the intercalated state.     

Sub-microsecond chlorophyll A delayed fluorescence from Photosystem I Magnetic field-induced increase of the emission yield

(1) In photosystem I (PS I) particles in the presence of dithionite and intense background illumination at 290 K, an external magnetic field (0–0.22 T) induced an increase, ΔF, of the low chlorophyll a emission yield, F ($\text{ΔF}\text{F}\text{? 1–1.5\%}$). Half the effect was obtained at about 35–60 mT and saturation occurred for magnetic fields higher than about 0.15 T. In the absence of dithionite, no field-induced increase was observed. Cooling to 77 K decreased ΔF at 685 nm, but not at 735 nm, to zero. Measuring the emission spectra of F and ΔF, using continuous excitation light, at 82, 167 and 278 K indicated that the spectra of F and ΔF have about the same maximum at about 730, 725 and 700 nm, respectively. However, the spectra of ΔF show more long-wavelength emission than the corresponding spectra of F. (2) Only in the presence of dithionite and with (or after) background illumination, was a luminescence (delayed fluorescence) component observed at 735 nm, after a 15 ns laser flash (530 nm), that decayed in about 0.1 μs at room temperature and in approx. 0.2 μs at 77 K. A magnetic field of 0.22 T caused an appreciable increase in luminescence intensity after 250 ns, probably mainly caused by an increase in decay time. The emission spectra of the magnetic field-induced increase of luminescence, ΔL, at 82, 167 and 278 K coincided within experimental error with those of ΔF mentioned above. The temperature dependence of ΔF and ΔL was found to be nearly the same, both at 685 and at 735 nm. (3) Analogously to the proposal concerning the 0.15 μs luminescence in photosystem II (Sonneveld, A., Duysens, L.N.M. and Moerdijk, A. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 5889–5893), we propose that recombination of the oxidized primary donor P-700⁺ and the reduced acceptor A^?, probably A^?₁, of PS I causes the observed fast luminescence. The effect of an external magnetic field on this emission may be explained by the radical pair mechanism. The field-induced increase of the 0.1–0.2 μs luminescence seems to be at least in large part responsible for the observed increase of the total (prompt + delayed) emission measured during continuous illumination in the presence of a magnetic field.     

Luminescent dinuclear gold complexes of bis(diphenylphosphano)acetylene

We have synthesized a series of dinuclear gold(I) derivatives with the diphosphane bis(diphenylphosphano)acetylene, namely [(AuX)₂(μ-dppa)] (X=Cl, C₆F₅, SC₆F₅, S₂CN(CH₂Ph)₂). X-ray structure determinations for the first three derivatives reveal a linear geometry for the gold centres. There are no intramolecular gold-gold interactions, although for X=Cl intermolecular gold(I)-gold(I) interactions of 3.0694(4) Å lead to an infinite twisted chain; the further presence of C-H?Cl contacts leads to a more complex three-dimensional structure. All the derivatives are luminescent in the solid state at low temperature in the range 455-593 nm; most of them are emissive at room temperature in the range 470-598 nm. We have also prepared the dinuclear gold(III) derivative [(Au(C₆F₅)₃)₂(μ-dppa)]. Finally, we have prepared the derivative [(AuCl)₂(μ-dppa)₃], which forms a cage with two tetrahedrically coordinated gold(I) centres at the apical positions bridged by three rigid diphosphane ligands, with a helical twist of 26.2°, and a gold-gold distance of 5.769 Å. The gold(III) and the four-coordinate gold(I) derivatives are not luminescent.