Reaction Of Bis Research Articles

Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy.

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction 10B (n, alpha) 7Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, "AB-type" Lactosome® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the "molecular glue" effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either 10B-Carb or 10B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any 10B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with 10B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., "theranostics".

Ortho-functionalized pyridinyl-tetrazines break the inverse correlation between click reactivity and cleavage yields in click-to-release chemistry

The bioorthogonal tetrazine-triggered cleavage of trans-cyclooctene(TCO)-linked payloads has strong potential for widespread use in drug delivery and in particular in click-cleavable antibody-drug conjugates (ADCs). However, clinical translation is hampered by an inverse correlation between click reactivity and payload release yield, requiring high doses of less reactive tetrazines to drive in vivo TCO reactions and payload release to completion. Herein we report that the cause for the low release when using the highly reactive bis-(2-pyridinyl)-tetrazine is the stability of the initially formed 4,5-dihydropyridazine product, precluding tautomerization to the releasing 1,4-dihydropyridazine tautomer. We demonstrate that efficient tautomerization and payload elimination can be achieved by ortho-substituting bis-pyridinyl-tetrazines with hydrogen-bonding hydroxyl or amido groups, achieving a.o. release yields of 96% with 18-fold more reactive tetrazines. Applied to on-tumor activation of a click-cleavable ADC in mice, these tetrazines afforded near-quantitative ADC conversion at a ca. 10- to 20-fold lower dose than what was previously needed, resulting in a strong therapeutic response.

Ambidentate behavior of oximate in VO(OMe)2+ and VO2 + complexes with biacetylmonoxime 4-R-benzoylhydrazones: syntheses, structures, and properties

Reactions of bis(acetylacetonato)oxovanadium(IV), [VO(acac)2], with biacetylmonoxime 4-R-benzoylhydrazones (H2L1 (R = Me) and H2L2 (R = OMe), where 2Hs represent the dissociable oxime and amide protons) in 1:1 mole ratio in methanol result in complexes [VO(OMe)(MeOH)(L1)] (1) and [VO(μ-OMe)(L2)]2 (2). When reactions were performed in the presence of two molar equivalents of KOH, K[VO2(L1)]·MeOH (3) and K[VO2(L2)]·2MeOH (4) were obtained. The complexes have been characterized using elemental analysis and mass spectrometry along with magnetic, solution electrical conductivity, thermogravimetric, various spectroscopic (IR, UV-Vis, and 1H NMR), and cyclic voltammetric measurements. The molecular structures of H2L1 and complexes 1-4 were determined by single-crystal X-ray crystallographic studies. In both 1 and the dimethoxo bridged centrosymmetric 2, the metal centers are in distorted octahedral NO5 environment, where (L1/2)2− meridionally coordinate the respective metal centers through the amidate-O, imine-N, and oximate-O and form fused 5,6-membered chelate rings. In 3 and 4, the metal centers have distorted trigonal bipyramidal N2O3 coordination spheres, where the fused 5,5-membered chelate rings forming amidate-O, imine-N, and oximate-N donors (L1/2)2− occupy the axial-equatorial-axial positions. The physical properties of all four complexes are consistent with their molecular formulas and structures.

Indication of p + 11B reaction in Laser Induced Nanofusion experiment

The NanoPlasmonic Laser Induced Fusion Energy (NAPLIFE)1 project proposed fusion by regulating the laser light absorption via resonant nanorod antennas implanted into hydrogen rich urethane acrylate methacrylate (UDMA) and triethylene glycol dimethylacrylate (TEGDMA) copolymer targets. In part of the tests, boron-nitride (BN) was added to the polymer. Our experiments with resonant nanoantennas accelerated protons up to 225 keV energy. Some of these protons then led to p + 11B fusion, indicated by the sharp drop of observed backward proton emission numbers at the 150 keV resonance energy of the reaction. The generation of alpha particles was verified by CR-39 (Columbia Resin #39) nuclear plastic track detectors.

Development of phosphine and diimine stabilized copper(I) catalysts for efficient azide–alkyne cycloaddition

The synthesis of a small family of copper(I) complexes bound to diimine and phosphine ligands, and their characterization, spectroscopic properties and application as pre-catalyst for azide–alkyne cycloaddition reaction are reported. Reaction of bis-(N-aryl)glyoxaldimine (p-R-C6H4NC(H)(H)CNC6H4-R-p; R = OCH3, CH3 and Cl; abbreviated as L-R) with [Cu(PPh3)2(NO3)] in refluxing methanol affords a group of three mixed-ligand copper(I) complexes of type [Cu(PPh3)2(L-R)]NO3, depicted respectively as complex 1 (R = OCH3), 2 (R = CH3) and 3 (R = Cl). Crystal structures of 1–3 have been determined by X-ray diffraction analysis. In each complex, the copper(I) center is nested in a nearly tetrahedral N2P2 coordination environment. Complexes 1–3 exhibit two intense absorptions spanning over the visible and ultraviolet regions. Origin of these absorptions was probed with DFT and TDDFT calculations, which revealed that the lower energy absorption at 346–380 nm is due to an allowed copper-to-diimine charge-transfer transition, and the second absorption near 270 nm is largely due to an intra-phosphine charge-transfer transition. These complexes also show prominent emission spectra while excited at 320 nm. These copper(I) complexes are found to serve as efficient precursor for catalytic azide–alkyne cycloaddition reaction under relatively mild condition, and offering a broad substrate scope.

Re-investigation of the interplay of fission modes and non-equilibrium fission processes in heavy actinide nuclei 249Bk and 257Md

Measurements of mass and angular distributions of fission fragments from actinide nuclei 249Bk and 257Md, produced in fusion reactions 11B and 19F + 238U, are presented. Experimentally observed mass ratio distributions indicate “multi-chance fission” through the interplay of fission modes in the fission process, and they agree well with predictions from calculations using the GEF (“GEneral description of Fission observables”) model code. Furthermore, to test the signatures of events from non-compound nuclear processes in the fission of 249Bk and 257Md nuclei, Monte Carlo statistical decay model calculations using GEMINI++ were performed for the measured mass distribution at all energies. For comparison purposes, the fission fragment mass distributions of neighboring heavy actinide nuclei, previously measured in the fission of 250Cf and 254Fm nuclei produced by 12C and 16O projectiles on a 238U target, are also presented. The measured angular anisotropy data for the 19F + 238U reaction differ from the results of the Transition State Model (TSM) at energies below the fusion barrier. As a result of the present study, we suggest considering the interplay between K relaxation time, dynamic dissipation, and their influence on shell correction to understand the evolution of fission dynamics in heavy-ion-induced actinide nuclei.

Synthesis and structural characterization of a novel large type double-layered cyclophanes based on the reaction of bis(N-alkylene benzothiazolium) dibromide and triethylamine

The synthesis of a novel large type double-layered cyclophanes has been successfully accomplished by free radical coupling reaction with the bis(N-alkylene benzothiazolium) dibromide salts as their important synthetic intermediates. The structures of the two-layered cyclophanes and the synthetic intermediates have been elucidated based on the NMR data and X-ray structural analysis, respectively. The two-layered cyclophanes consist of two different geometries, anti-two cyclic lactam amide rings inside and two bridges of disulfide bonds outside, which are unique and novel structures. Their physical properties were investigated by UV–Vis and redox potential, too.

Differential cross-section measurement for 10B(p, αγ1)7Be, 10B(p, p’γ1)10B and 11B(p, p’γ1) 11B reactions

Differential cross-sections of the 10B(p, αγ1)7Be (Eγ = 429 keV), 10B(p, p’γ1)10B (Eγ = 718 keV) and 11B(p, p’γ1) 11B (Eγ = 2124 keV) reactions have been measured at proton laboratory energies of 912–2776 keV at 90°. The proton beam impinged on a thin natB2O3 film evaporated onto a self-supporting thin carbon layer. The incident energies were increased by 10 (20) keV steps in the resonance (off-resonance) regions. Our data are compared with the existing ones from literature. A benchmark procedure was performed by comparing the calculated thick-target yields from the current differential cross-sections with the existing measured thick target gamma-ray yields. The overall systematic uncertainty of the cross-sections was estimated to be about 10 %, mainly related to the target thickness determination.

Boron Neutron Capture Therapy-Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy.

Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT-EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high-linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs-educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti-tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long-term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Interplay of single-particle and collective modes in the 12C(p,2p) reaction near 100 MeV

The 12C(p,2p)11B reaction at Ep=98.7 MeV proton beam energy is analyzed using a rigorous three-particle scattering formalism extended to include the internal excitation of the nuclear core or residual nucleus. The excitation proceeds via the core interaction with any of the external nucleons. We assume the 11B ground and low-lying excited states [32− (0.0 MeV), 52− (4.45 MeV), 72− (6.74 MeV)] and the excited states [12− (2.12 MeV), 32− (5.02 MeV)] to be members of K=32− and K=12− rotational bands, respectively. The dynamical core excitation results in a significant cross section for the reaction leading to the 52− (4.45 MeV) excited state of 11B that cannot be populated through the single-particle excitation mechanism. The detailed agreement between the theoretical calculations and data depends on the used optical model parametrizations and the kinematical configuration of the detected nucleons.

Chemical Reaction Modulated Low-Dimensional Phase Toward Highly Efficient Sky-Blue Perovskite Light-Emitting Diodes.

Blue perovskite light-emitting diodes (PeLEDs) are crucial avenues for achieving full-color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi-two-dimensional (quasi-2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low-dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n-phase structures in quasi-2D perovskite films. The results reveal that the highly reactive bis(4-(trifluoromethyl)phenyl)phosphine oxide (BTF-PPO) molecule could effectively restrain the formation of organic spacer cation-ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6 % (@ 490 nm). The finding provides a new route to design dopant molecules for phase modulation in quasi-2D PeLEDs.

Chemical Reaction Modulated Low‐Dimensional Phase Toward Highly Efficient Sky‐Blue Perovskite Light‐Emitting Diodes

Blue perovskite light‐emitting diodes (PeLEDs) are crucial avenues for achieving full‐color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi‐two‐dimensional (quasi‐2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low‐dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n‐phase structures in quasi‐2D perovskite films. The results reveal that the highly reactive bis(4‐(trifluoromethyl)phenyl)phosphine oxide (BTF‐PPO) molecule could effectively restrain the formation of organic spacer cation‐ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6% (@ 490 nm). The finding provides a new route to design dopant molecules for phase modulation in quasi‐2D PeLEDs.

Syntheses, Characterization, and Redox Activity of Ferrocene-Containing Titanium Complexes.

The chemistry of bis(π-η5:σ-η1-pentafulvene)titanium complexes is characterized by a broad range of E-H activation and Ti-C functionalization reactions, whereas ferrocene derivatives are easily accessible and redox-active compounds. The reaction of ferrocenealdehyde and -ketones with bis(π-η5:σ-η1-pentafulvene)titanium complexes result in the formation of bimetallic complexes via insertion of the C=O double bond of the aldehyde/ketone into the Ti-Cexo bond of the pentafulvene moiety. The reaction of bis(π-η5:σ-η1-pentafulvene)titanium complexes with ferrocenyl alcohols leads to alcoholate complexes via deprotonation of the OH group by the pentafulvene ligand. Because of the one remaining pentafulvene unit, further functionalization of the complexes is possible. In this work, we proceeded with 1,1'-bifunctionalized ferrocene derivatives for intramolecular follow-up reactions. 1,1'-Ferrocenedimethanol reacts with bis(π-η5:σ-η1-pentafulvene)titanium complexes in a double O-H deprotonation reaction to yield the dialcoholate complex. 1,1'-bis(phenylphosphine)ferrocene reacts differently as the double P-H deprotonation reaction results in the formation of a P-P linked phosphine. Therefore, we studied the reactivity of 1,1'-bis(phenylphosphine)ferrocene toward Rosenthal's reagent. As Rosenthal's reagent is regarded as a masked titanocene(II) species, it undergoes redox reactions toward H-acidic substrates, forming a paramagnetic Ti(III) complex.

M(TEIM) complexes with M as Co and Fe: Analogues of classic M(TIM)

The syntheses and characterization of Fe and Co complexes supported by a new tetra-imine macrocycle, TEIM (2,3,9,10-tetraethyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene), are reported. Templating with Co(OAc)2·4H2O yielded trans-[Co(TEIM)Cl2][PF6] (1a), which was converted to trans-[Co(TEIM)X2][PF6] (X = N3 (2a) and NO2 (3a)) through reactions with NaX (X = N3 or NO2). Templating with Fe generated trans-[Fe(TEIM)(NCCH3)2][PF6]2, which was oxidized to trans-[Fe(TEIM)Cl2][PF6] (1b). The reaction of 1b with NaN3 formed [Fe(TEIM)(N3)2][PF6] (2b) while the reaction with [Fe(TEIM)(NCCH3)2][PF6]2 and NaNO2 yielded trans-[Fe(TEIM)(NO2)2] (3b). Single crystal X-ray diffraction studies revealed a pseudo-octahedral geometry around the Co / Fe centers with the ethyl groups oriented above or below the plane of the TEIM ring. The absorption spectra of 1b displays weak charge transfer bands near the UV to visible region, while 2b and 3b displayed intense charge transfer bands within the visible region. Cyclic voltammograms of 1a revealed four 1 e− reductions while those of 2a and 3a display only three cathodically shifted reductions. Analogous studies of 1b and 2b revealed two 1 e- reductions while 3b displays only an oxidation event. EPR studies of ferric complexes 1b and 2b indicated a low spin d5 electronic figuration with S = ½ ground state.

Study of [formula omitted] reactions with polarized photons at energy 40-65 MeV

The photon beam asymmetry of the C12(γ→,p01)11B and C12(γ→,p2−6)11B reactions has been measured in the energy range 40–65 MeV, using a tagged, linearly-polarized photon beam at the MAX-lab facility in Sweden. The asymmetry of the C12(γ→,p01)11B reaction to ground and first excited state of B11 is Σ≈0.82 over the measured energy range. The main contribution to the C12(γ→,p2−6)11B reaction to higher excited states comes from processes in which the residual nucleus is in the 3/2−(5.02MeV) or 7/2−(6.74MeV) excited states. The asymmetry of this reaction is Σ≈0.6, close to the value for free deuteron photodisintegration.

Cryogenic solid deuterium target formation to realize highly pure deuteron acceleration by high-intensity laser

In recent years, laser-driven neutron sources have attracted attention for their applications such as nondestructive analysis and the production of medical radioisotopes. One of the efficient neutron production methods is the use of the 9Be(d, n)10B reaction on a beryllium target with deuterons accelerated by laser–plasma interactions, since this is an exothermic reaction. For efficient deuteron acceleration, we have developed a formation system for solid deuterium targets. A millimeter thick solid deuterium target can be formed with the system. Before the laser shot, the solid deuterium target in the laser chamber can be mechanically moved to the laser irradiation point. We have demonstrated deuteron acceleration by the LFEX laser, and a highly pure deuteron pulse with energies of up to 6.2 MeV was measured with a Thomson parabola ion spectrometer.

Radioisotope production using lasers: From basic science to applications

The discovery of chirped pulse amplification has led to great improvements in laser technology, enabling energetic laser beams to be compressed to pulse durations of tens of femtoseconds and focused to a few micrometers. Protons with energies of tens of MeV can be accelerated using, for instance, target normal sheath acceleration and focused on secondary targets. Under such conditions, nuclear reactions can occur, with the production of radioisotopes suitable for medical application. The use of high-repetition lasers to produce such isotopes is competitive with conventional methods mostly based on accelerators. In this paper, we study the production of 67Cu, 63Zn, 18F, and 11C, which are currently used in positron emission tomography and other applications. At the same time, we study the reactions 10B(p,α)7Be and 70Zn(p,4n)67Ga to put further constraints on the proton distributions at different angles, as well as the reaction 11B(p,α)8Be relevant for energy production. The experiment was performed at the 1 PW laser facility at Vega III in Salamanca, Spain. Angular distributions of radioisotopes in the forward (with respect to the laser direction) and backward directions were measured using a high purity germanium detector. Our results are in reasonable agreement with numerical estimates obtained following the approach of Kimura and Bonasera [Nucl. Instrum. Methods Phys. Res., Sect. A 637, 164–170 (2011)].

Cross section measurement for the 14N(n,α0,1)11B reactions in the 4.5–11.5 MeV neutron energy region

Cross section measurement for the 14N(n,α0,1)11B reactions in the 4.5–11.5 MeV neutron energy region

Zinc‐bis(imino)pyridine Complexes as Catalysts for Intermolecular Amidation of Benzylic C(sp3)−HBond

AbstractEfficient NNN‐pincer type bis(imino)pyridine ligand based zinc(II) catalyzed intermolecular amidation of benzylic hydrocarbons with sulfonamides has been developed. The zinc complexes were synthesized by the reaction of bis(imino)pyridine ligand with zinc(II) precursors such as Zn(OAc)2 ⋅ 2H2Oand ZnBr2. The structure of the bis(imino)pyridine‐Zn(OAc)2 complex was characterized by single crystal X‐ray diffraction. The zinc(II)‐bis(imino)pyridine complexes were utilized as catalysts for the intermolecular amidation of benzylic C(sp3)−H bond in the presence of N‐bromosuccinimide (NBS) as an oxidant. A broad range of substrates delivered the products in moderate to good yields. This protocol provides the synthesis of various amides viaC−H activation.

Germaborene reactivity study - addition of carbon nucleophiles, cycloaddition reactions, coordination chemistry.

MeNHC substituted germaborenium cation 2 was synthesized directly in reaction of bromo-substituted germaborene 1b with MeNHC. The adamantyl isonitrile substituted germaborenium cation 4 was obtained stepwise: substitution of the chloride atom against adamantyl isonitrile at the B-Cl unit in 1a, simultaneous migration of the chloride to the germanium atom followed by chloride abstraction using Na[BArF 4] gives the germaborenium cation 4. Substitution of the bromide atom in 1b against carbon monoxide followed by bromide abstraction using Ag[Al(OtBuF)4] leads to compound 6 exhibiting a B[double bond, length as m-dash]C double bond substituted at the boron atom by a germylium cation. Treating the germaborene [Ge[double bond, length as m-dash]B-Ph] (1c) with selenium, a cycloaddition product 7 was characterised featuring a GeBSe heterocycle. Carbon dioxide reacts with 1b to give a four membered ring molecule 8 as the product of a B-C and Ge-O bond formation. In reaction of 1b with dimethylbutadiene, a product 9 of a [2 + 4] cycloaddition was isolated. Transition metal fragments [Fe(CO)4 (10), CuBr (11), AuCl (12)] show coordination at the germaborene double bond. Molecular structures of the germaborene coordination compounds 10-12 are presented and the ligand properties are discussed. After treating the germaborene [Ge[double bond, length as m-dash]B-Br] (1b) with [Cp*Al]4, insertion of a Cp*Al moiety into the B-Br bond was found (13).