Determination of boron isotopic variations in aquatic systems with negative thermal ionization mass spectrometry as a tracer for anthropogenic influences

A technique for precise boron isotope ratio measurements with a high detection power has been developed by negative thermal ionization mass spectrometry (NTIMS). Relative standard deviations in the range of 0.03–0.3% have been obtained for the determination of the ¹¹B/¹⁰B isotope ratio using nanogram amounts of boron. Ba(OH)₂ has been applied as ionization promoter for the formation of negative thermal ions. By adding MgCl₂ better reproducibilities of the measurement have been achieved. A possible interference of BO^-₂ ions at mass number 42 by CNO^- could be excluded by the sample preparation technique used. Contrary to other NTI techniques no dependence of the measured isotope ratio on the boron amount used has been observed. Anthropogenic and natural saline influences in ground water have been successfully identified by boron isotope ratio determinations with this NTIMS method, due to the different isotopic composition of boron in natural and anthropogenic substances. In sewage, the boron isotope ratio is substantially influenced by washing powder, which contains low ¹¹B/¹⁰B ratios (expressed in ¹¹B values normalized to the standard reference material NIST SRM 951). In contaminated ground water, low ¹¹B values are normally correlated with high boron and high chloride concentrations. On the other hand, ¹¹B shifts to higher values in less contaminated samples. For ground water with saline influences, only the ¹¹B determination, and not the boron or chloride content, allowed the correct identification of this natural source of contamination.     

The Role of Chemistry in the Development of Boron Neutron Capture Therapy of Cancer

A therapeutic method that selectively destroys malignant cells in the presence of normal cells is a highly valued goal of oncologists and the possible salvation of cancer patients afflicted with some incurable forms of the disease. Selective cell destruction is, in principle, possible with a binary therapeutic strategy based upon the neutron capture reaction observed with the ¹⁰B nucleus and a neutron of low kinetic energy (thermal neutron). This nuclear fission reaction produces both ⁴He and ⁷Li⁺ nuclei along with about 2.4 MeV of kinetic energy and weak γ-radiation. Since the energetic and cytotoxic product ions travel only about one cell diameter in tissue one may specify the cell type to be destroyed by placing innocent ¹⁰B nuclei on or within only the doomed cells. This article describes the current status of chemical research aimed at the eventual adoption of this therapeutic method (boron neutron capture therapy or BNCT). The multidisciplinary nature of this research effort involves chemistry, biology, nuclear physics, medicine, and related specialties. Methods devised for bringing ¹⁰B nuclei to tumor cells in therapeutic amounts are correlated with the structure of a generalized cell and the various cellular compartments available for boron localization. The synthesis methods employed for the creation of boron-containing biomolecules and drugs are presented along with representative data concerning their efficacy in tumor localization. The outlook for BNCT is especially bright at this time because of rapid developments in the fields of bioorganometallic chemistry, microbiology, immunology, and nuclear science, to name but a few. Very effective boron delivery vehicles have been demonstrated, and through the interaction of chemistry and biology these species are undergoing further improvement and evaluation of their suitability for BNCT.     

Determination of boron in glass by alpha-spectrometry

Alpha-spectrometric method has been used for the determination of boron in borosilicate glasses. For irradiation thermal neutrons with a flux of about 10⁵ n·cm^–2·s^–1, produced in a paraffin moderator surrounding a deuteron target of a small neutron generator, were used. Alpha-particles from the reaction¹⁰B(n, ) were detected by a Si solid state detector with a resolution of about 50 keV. The sensitivity of the method is 0.05 wt % boron in glass samples.This work was supported by the Hungarian Research Foundation (Contract No. 1734/91.).     

Some problems associated with the use of boron carbide neutron filters for reactor epithermal neutron activation analysis (ENAA)

The radiation heating caused by the¹⁰B(n, )⁷Li-reaction in boron carbide (B₄ C) neutron filters used for epithermal neutron activation analysis has been examined by measuring rates of temperature rise and steady-state temperatures of sintered and powdered B₄C filters placed in dry air and reactor pool-water during irradiation, respectively. Maximum equilibrium temperatures of 195°C for air-cooled sintered, and 50°C for water-cooled powdered B₄C were observed, confirming the necessity for efficient cooling of the filter during irradiation. It is noted that the accumulation of the¹⁰B(n, )⁷Li-reaction products in B₄C and other boron compounds may severely limit the reuse of the filters in subsequent irradiations.     

Determination of trace concentration of boron in ADU by the nuclear track technique

A method for the determination of boron concentration in extracted (NH₄)₂ U₂O₇·H₂O (ADU) has been used. One ml of the aqueous solution is irradiated with thermal neutrons from a 10 Ci Am/Be neutron source with a flux of 0.2·10⁵ n·cm^–2·s^–1 and thermal column in the IRT-5000 with a flux of about 10⁷ n·cm^–2·s^–1. The alpha-activity due to the reaction¹⁰B(n, )⁷Li is recorded by a CR-39 alpha track detector. After the exposure, the alpha tracks are made visible in an optical microscope at magnification of 800X by etching the detector in 6N NaOH, and the track density is determined using calibration curves of known concentrations of boron. The boron concentration of the extracted ADU was found to be 5 ppm.     

Monitoring of gamma emission and neutron transmission during boron neutron capture treatment delivery

The ability to map boron and hydrogen distributions in the body is paramount to the success of boron neutron capture therapy (BNCT). We investigated treatment-time quantitative mapping of these distributions by detecting (i) 0.48 MeV de-excitation photons from neutron capture by boron-10; (ii) 2.22 MeV photons from neutron capture by hydrogen; and (iii) transmitted neutrons. Monte Carlo simulations reported no detectable difference when ¹⁰B in tumour was varied from 0 to 50 ppm, and when the tumour size was varied from 0.0 to 9.5 cm³.     

Determination of boron in the thin surface layer of a silicon wafer by instrumental charged particle activation analysis

Instrumental charged particle activation analysis (CPAA) for determining boron in a thin surface layer of silicon was developed. The nuclear reaction and incident energy were selected in order to minimize any interference from surface or bulk impurities. Thin boron film was used as a standard sample and its boron content was determined by neutron induced prompt -ray analysis. As a result, we were able to determine¹¹B and¹⁰B at 10¹⁵ atoms/cm² with an accuracy of better than 3% by 4 MeV proton and 7 MeV -bombardment, respectively. Each boron isotope could be determined down to 10¹³ atoms/cm². Our CPAA was applied to determine boron in a boron implanted silicon wafer of a SIMS standard sample.     

Synthesis of dodecaborate-conjugated cholesterols for efficient boron delivery in neutron capture therapy

Dodecaborate-conjugated cholesterols 3a-c were synthesized for liposomal boron delivery systems in neutron capture therapy. The current synthesis is based on the S-alkylation protocol of the cyanoethyl-protected BSH with alkyl halides. The dodecaborate-conjugated cholesterol 3a liposome, which was prepared from dimyristoylphosphatidylcholine (DMPC), cholesterol, dodecaborate-conjugated cholesterol 3a, and polyethyleneglycol-conjugated distearoylphosphatidylethanolamine (PEG-DSPE) (1:0.5:0.5:0.1), exhibited higher cytotoxicity than BSH at the same boron concentration and IC₅₀ values of the 3a liposome and BSH toward colon 26 cells were estimated as 25 and 78 ppm of boron concentration, respectively.     

Determination of boron in magnesium oxide by charged particle activation analysis

The determination of boron in magnesium oxide using the¹⁰B/p, /⁷Be,¹⁰B/d, n/⁷Be, and¹⁰B/d, n/¹¹C reactions is described. Lithium interferes the nuclear reactions leading to beryllium-7. Combination of a proton and deuteron irradiation, each followed by measurement of the induced beryllium-7 activity, allows a simultaneous determination of boron and lithium. The¹⁰B/d, n/¹¹C reaction is free from nuclear interferences. The boron concentration ranges from 1.5 to 850 g g^–1. The results obtained by the two methods are in good agreement.Senior Research Associate of the Belgian National Fund for Scientific Research.     

Boron‐Containing Protoporphyrin IX Derivatives and Their Modification for Boron Neutron Capture Therapy: Synthesis,Characterization, and Comparative In Vitro Toxicity Evaluation

A novel series of boronated porphyrins for potential use in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) for tumor suppression is described. Protoporphyrin IX {i.e., bis(α‐methyl‐β‐pentylethylether)protoporphyrin IX, and bis(α‐methyl‐β‐dodecanylethylether)protoporphyrin IX} bearing polyhedral borane anions (B₁₂H₁₁SH^2?, B₁₂H₁₁NH₃^?, or B₁₂H₁₁OH^2?) were synthesized with reasonable yields. Modification of the protoporphyrin IX structure was achieved by variation of the lengths of the alkyl chains (pentyl and dodecanyl) attached through ether linkages to the former vinyl groups. The goal of this modification was to develop boronated porphyrins with chemical and physical properties that differed from those of protoporphyrin IX. Performance of an MTT assay with each derivative revealed that the synthesized boronated porphyrins showed low cytotoxicities in a variety of cancer cells. Of these compounds, B₁₂H₁₁NH₂^2?‐conjugated porphyrin induced a significant increase in the level of boron accumulation and PDT efficacy against HeLa cells.     

A gas flow proportional detection system for the determination of boron in aerosol samples and other sample types

This work describes the design, fabrication, and testing of a lucite bodied proportional gas detection system for the analysis of boron in selected samples via detection of the charged particles produced in the 10B(n,)⁷Li reaction induced by thermal neutrons. The detector was designed for internal placement of samples; the sample types of major interest were airborne aerosols collected on filters or particulate impaction plates. Samples were irradiated with the detector in the thermal neutron field produced in the graphite thermal column of the University of Lowell's one megawatt research reactor. Determined sensitivities for boron varied from 6.2·10^–8 to 1.73·10^–6 cpm·ng^–1 (n·cm^–2J·s^–1)^–1 depending on the physical characteristics of the samples. For a nominal counting time of ten minutes the lower limit of mass detection of natural boron was determined to be 12.1 nanograms. The analytical method was applied to the estimation of boron in fourteen samples of natural aerosols collected on membrane filters. Analysis of prepared samples and natural aerosol samples by ICP emission showed good agreement with analysis via the (n,) reaction. Application of the method to other sample types was demonstrated by the determination of boron in samples of borosilicate glass and borated polyethylene.     

Determination of traces of boron and cadmium in manganese sulphate solutions

Summary A well established method to calibrate ²⁵²Cf neutron sources makes use of a manganese bath technique based on the measurement of the induced ⁵⁶Mn-,-radioactivity. The knowledge of the impurities present in the bath is required because they may affect the results of the source strength measurements by their neutron absorption properties. Some specific impurities which may introduce a significant correction must be quantified and selective methods have to be used for their determination. The determination of two of these specific impurities, having a high capture cross section for neutrons, the boron and the cadmium, is described; it is based on spectrophotometry with curcumin (for B) and on pulse polarography (for Cd). Analytical results obtained on baths prepared in different laboratories are given. Errors are ±4–7% for B and ±3% for Cd.

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Bestimmung von Bor- und Cadmiumspuren in Mangansulfatlösungen

Zusammenfassung Eine übliche Methode zur Eichung von ²⁵²Cf-Neutronenquellen basiert auf der Manganbad-Technik, wobei die induzierte ⁵⁶Mn-,-Aktivität gemessen wird. Die Ergebnisse können durch Verunreinigungen des Bades beeinflußt werden. Methoden zu deren selektiver Erfassung sind daher notwendig. Die Bestimmung von Bor und Cadmium, die einen besonders hohen Einfangquerschnitt für Neutronen haben, wird beschrieben. Sie beruht auf der spektralphotometrischen Bestimmung mit Curcumin (für B) bzw. auf der pulspolarographischen Bestimmung (für Cd). Analysenwerte für verschiedene MnSO₄-Bäder werden verglichen. Die Fehler liegen im Bereich von ±4–7% (für B) und ±3% (für Cd).

     

Design Features of a Prompt Gamma Neutron Activation Analysis System at HANARO

The design features are described of a prompt gamma neutron activation analysis system at HANARO, a 30 MW research reactor in the Korea Atomic Energy Research Institute. The beam consists of polychromatic thermal neutrons diffracted by a set of pyrolytic graphite crystals at orders n in the range 1n6 at a Bragg angle of 45° on a horizontal beam line. A neutron flux of 1.0·10⁸ n·cm^–2·s^–1 is calculated at the sample position from the reflectivity of the crystal which has been confirmed in a measurement of a diffracted neutron spectrum using a time-of-flight spectrometer and gold-wire activation. The fast neutron and gamma backgrounds will be low due to the use of a diffracted beam and a tapered collimator. The detection system comprises a 30% n-type HPGe detector, signal electronics and a fast ADC. The first application of this system will be the analysis of boron concentration in biological samples for neutron capture therapy. Construction of the beam line and the arrangement of the detection system is proceeding.     

Synthesis of a Tyr-octreotate conjugated closo-carborane [HC2B10H10]: a potential compound for boron neutron capture therapy

A novel Tyr³-octreotate conjugated closo-carborane as a potential compound for boron neutron capture therapy was obtained via Fmoc solid phase peptide synthesis. The boron cluster [C₂B₁₀H₁₁] was introduced through the reaction of 6,9-bis(acetonitrile)decaborane and 5-hexynoic acid yielding a new closo-carborane conjugated carboxylic acid which was coupled subsequently with solid phase conjugated Tyr³-octreotate. The final boron-containing peptide was purified by preparative reverse phase HPLC and structural identity was proved applying MALDI-TOF mass spectrometry.     

Prompt gamma as a fluence rate monitor in neutron beam experiments

An accurate measurement of the neutron lifetime requires a determination of neutron fluence rate to an accuracy of a few tenths of a percent. The¹⁰B(n,)⁷ Li reaction offers the possibility of achieving this uncertainty. The thermal cross section is large and its departure from 1/v behavior is about 3 parts in 10000. The principal alpha branch is to the first excited state of⁷Li which then decays by emission of a 478 keV gamma ray. The measurement of the gamma branch can be made with boron samples that totally absorb thermal neutrons, allowing greater sensitivity and eliminating the uncertainty of target thickness. The absolute efficiency of the gamma detector can be determined by an alpha-gamma coincidence technique. Preliminary investigations of this method are presented with a discussion of the problems that must be overcome to achieve the desired uncertainty.Work supported in part by the Department of Energy     

Synthesis of conjugates of closo-dodecaborate dianion with cholesterol using a “click” reaction

The nucleophilic ring-opening reaction of tetrahydropyran derivative of the closo-dode-caborate dianion with sodium azide in the presence of tetrabutylammonium bromide led to the novel azido-derivatives of[B₁₂H₁₂]^2?. A Cu-catalyzed 1,3-dipolar [3+2] cycloaddition reaction of the closo-dodecaborate dianion azido-derivatives with alkynyl-cholesterol led to 1,4-disubstituted 1,2,3-triazoles with the closo-dodecaborate fragment at position 1. The resulting conjugates are potentially suitable for the development of liposomal drugs to selectively deliver boron into a tumor cell for boron neutron capture therapy of cancer.

     

Synthesis of carboxylic acids based on the closo-decaborate anion

A series of new boron-containing carboxylic acids was prepared by the ring-opening reaction of cyclic oxonium derivatives of the closo-decaborate anion [B₁₀H₁₀]²⁻ with methyl esters of hydroxybenzoic acids or the cyanide anion followed by hydrolysis of the obtained nitrile and esters. Acid hydrolysis of the esters results in protonation of the oxygen atom connected to the boron cage, with the formation of the corresponding O-protonated acids, isolated in the solid state. The compounds synthesized can be used in radionuclide diagnostics and boron neutron capture therapy of cancer.     

Designed Boron-Rich Polymeric Nanoparticles Based on Nano-ion Pairing for Boron Delivery

Boron-rich particles with the boron fraction ca.10–20 wt % of controllable shape and size that can be easily prepared via simple ion co-assembly are promising material for tumor treatment by boron neutron capture therapy. Electroneutral, dynamic core-shell polymeric nanoparticles were prepared by co-assembly of cationic PEO-block-PGEA diblock copolymer with sodium closo-dodecaborate, Na₂[B₁₂H₁₂]. This is the first example of polymer nanoparticles based on [B₁₂H₁₂]²⁻nano-ion pairing. The high [B₁₂H₁₂]²⁻ loading is proven by calorimetry at physiological salt concentration. As a result of rational design, rod-, worm- and sphere-like particles were produced and further tested using human glioblastoma and cervical carcinoma cell lines. Rod-like particles yielded the highest internalization capability in all tested cell lines.     

Synthesis,reactivity, in vitro boron neutron capture therapy assay,and molecular docking of fluorocyclocarboxyboranylamine

The one-pot reaction of Me₃NBH₂CN with Et₃O⁺BF₄⁻ followed by addition of BF₃·Et₂O and water produces a trimethylamine derivative of fluorocyclocarboxyboranylamine, Me₃NBH₂C(O₂BF₂NH₂) ( 1 ) in 36.0% yield. Compound 1 undergoes exchange reaction between the exo-Me₃N moiety and piperidine or pyridine to produce the corresponding piperidine-substituted fluorocyclocarboxyboranylamine ( 2 ) or pyridine-substituted fluorocyclocarboxyboranylamine ( 3 ) in 51.2% or 42.4% yields, respectively. The new compounds were characterized by ¹H, ¹³C, ¹¹B, and ¹⁹F nuclear magnetic resonance spectroscopy; Fourier-transform infrared spectroscopy; and elemental analyses and the crystal structure of 1 was determined to confirm its molecular geometry. The in vitro killing effects of 1 , along with its toxicity measurements and molecular docking interactions with matrix metalloproteinases showed a potential promise of such species as both boron neutron capture therapy and boron neutron capture synovectomy agents in the treatment of tumors and rheumatoid arthritis, respectively, in the presence of slow neutrons.     

Application of an image scanner for determination of boron in glass by a nuclear track technique

For boron concentration in the range of 010%, a 600 g²⁵²Cf neutron source was used for thermal neutron irradiation. As for the track counting technique, a visual observation method by human eye and an automatic counting method with an image scanner showed a good agreement between the determinations by both methods. The latter is useful for improving accuracy in elemental determination by using the nuclear track technique because it gives reproducible count values which are free from human error in comparison with the former.