A Study of the Reaction of Hydroxide Ion with B20H18-2

Hawthorne, M. Frederick; Philling, Richard L.; Garrett, Philip M.

doi:10.1021/ja00949a013

Cited by 29 publications

(25 citation statements)

References 2 publications

(3 reference statements)

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“…Successful therapy requires the site-specific delivery of relatively large amounts (15)(16)(17)(18)(19)(20) jig of B per g of tissue) of boron to tumors (2). Strategies employed have included the use of boron compounds with some natural affinity for tumors, such as 4-(dihydroxyboryl)phenylalanine (BPA) (3) or the mercaptoundecahydro-closo-dodecaborate dianion (B12H,,SH2-; BSH) (4); the attachment ofboron-containing species to other molecules such as porphyrins (5); and the conjugation of boron-rich compounds with tumor-specific monoclonal antibodies and their fragments (6).…”

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confidence: 99%

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Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

Shelly

Feakes

Hawthorne

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

151

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The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective concentration of boron-10 within malignant tumors. The potential of liposomes to deliver boron-rich compounds to tumors has been assessed by the examination of the biodistribution of boron delivered by liposomes in tumor-bearing mice. Small unilamellar vesicles with mean diameters of 70 nm or less, composed of a pure synthetic phospholipid (distearoyl phosphatidylcholine) and cholesterol, have been found to stably encapsulate high concentrations of water-soluble ionic boron compounds. The hydrolytically stable borane anions B,.H01, B,2H11SH2-, B20H170H4-B2]HT3, and the normal form and photoisomer of B2oH 2-were encapsulated in liposomes as their soluble sodium salts. The tissue concentration of boron in tumor-bearing mice was measured at several time points over 48 h after i.v. injection of emulsions of liposomes containing the borane anions. Although the boron compounds used do not exhibit an affinity for tumors and are normally rapidly cleared from the body, liposomes were observed to selectively deliver the borane anions to tumors. The highest tumor concentrations achieved reached the therapeutic range (>15 jtg of boron per g of tumor) while maintaining high tumor-boron/blood-boron ratios (>3). The most favorable results were obtained with the two isomers of B2OH _. These boron compounds have the capability to react with intracellular components after they have been deposited within tumor cells by the liposome, thereby preventing the borane ion from being released into blood.Boron neutron-capture therapy (BNCT), first proposed by Locher in 1936 (1), is based upon the propensity of the 10B nucleus to undergo the 10B + 1n -* 'Li + 'He reaction with thermal neutrons. This process releases 2.28 MeV of kinetic energy, which is distributed between the a-particle and the 7Li+ ion. The effective distance of travel of these two ions in tissue is limited to approximately one cell diameter. During their passage through the interior of a cell, the energetic fission products cause ionization-tracking and cellular damage with associated cytotoxicity. Since the neutron capture cross-section of the 10B nucleus is 103 to 104 greater than that of all elements of physiological importance, the selective concentration of 10B atoms within cancer cells, followed by irradiation with thermal neutrons, should result in the destruction of the tumor cells even in the presence of neighboring normal cells.The development of effective targeting strategies for the selective transport ofboron to cancer cells has been the single most urgent problem in the area of BNCT. Successful therapy requires the site-specific delivery of relatively large amounts (15-20 jig of B per g of tissue) of boron to tumors (2). Strategies employed have included the use of boron compounds with some natural affinity for tumors, such as 4-(dihydroxyboryl)phenylalanine (BPA) (3) or the mercaptoundecahydro-closo-dodecaborate dianion (B12H,,SH2-; BSH) (4); the attac...

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confidence: 99%

“…The polyhedral borane anion derivatives used were prepared by published methods (17)(18)(19)(20)(21). Disodium mercaptoundecahydro-closo-dodecaborate (Na2B12Hi1SH) was a gift from the Callery Chemical (Pittsburgh).…”

mentioning

confidence: 99%

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

Shelly

Feakes

Hawthorne

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

151

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“…The substitution chemistry of the normal isomer of [B 20 H 18 ] 2Ϫ was first investigated by Hawthorne and coworkers (8,9). Nucleophilic attack on the electron-deficient threecenter two-electron bonds of [B 20 , with the hydroxide substituent located on the equatorial belt adjacent to the intercage linkage, as shown in Scheme 1, where E ϭ BH and F ϭ B. Acidcatalyzed rearrangement of the apical-equatorial isomer yielded the thermodynamically stable apical-apical (a 2 ) isomer.…”

Section: ϫmentioning

confidence: 99%

“…Nucleophilic attack on the electron-deficient threecenter two-electron bonds of [B 20 , with the hydroxide substituent located on the equatorial belt adjacent to the intercage linkage, as shown in Scheme 1, where E ϭ BH and F ϭ B. Acidcatalyzed rearrangement of the apical-equatorial isomer yielded the thermodynamically stable apical-apical (a 2 ) isomer. Analogous reactions also have been reported for the synthesis of alkoxy and amine derivatives (5,9,10 The utility of this class of compounds for BNCT has been investigated (4,5). Tumor-selective unilamellar liposomes, capable of delivering their contents intracellularly (11), were used as delivery vehicles for the compounds, which have little inherent tumor specificity.…”

Section: ϫmentioning

confidence: 99%

“…Initial interest in this compound was derived from the large boron content per unit charge and the known susceptibility of the anion to nucleophilic attack. The anion is also synthesized in two high yield reactions, amenable to boron-10 enrichment, from decaborane, B 10 H 14 (6, 7).The substitution chemistry of the normal isomer of [B 20 H 18 ] 2Ϫ was first investigated by Hawthorne and coworkers (8,9). Nucleophilic attack on the electron-deficient threecenter two-electron bonds of [B 20 , with the hydroxide substituent located on the equatorial belt adjacent to the intercage linkage, as shown in Scheme 1, where E ϭ BH and F ϭ B. Acidcatalyzed rearrangement of the apical-equatorial isomer yielded the thermodynamically stable apical-apical (a 2 ) isomer.…”

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confidence: 99%

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Synthesis andin vivomurine evaluation of Na₄[1-(1′-B₁₀H₉)-6-SHB₁₀H₈] as a potential agent for boron neutron capture therapy

Rc²,

Dk³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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Boron neutron capture therapy (BNCT), a binary cancer therapy first proposed by Locher in 1936 (1), is based on the propensity of the boron-10 isotope to capture thermal neutrons. The neutron capture reaction yields an unstable boron-11 atom, which then undergoes fission to produce highly energetic lithium-7 and helium-4 species. The two fission products have an effective range of Ϸ10 m in tissue, which essentially limits the fission event to a single cell or its immediate neighbors. Therefore, the selective concentration of boron-10 nuclei within tumor cells, followed by thermal neutron capture, should result in the localized destruction of malignant cells even in the presence of normal neighboring cells.The successful application of BNCT depends on the identification and production of boron-containing compounds, which are accumulated in significant amounts (Ͼ15 g of B per g of tumor; ref.2) by the tumor through natural mechanisms, or, alternatively, on the identification of a tumor-specific delivery modality, which would enable the delivery of boroncontaining compounds that have no inherent tumor specificity. Although the utility of tumor-targeted monoclonal antibody conjugates has been investigated, limited success has been achieved because of the highly competitive loss of conjugate to the liver once sufficient amounts of boron have been conjugated to the antibody (3).The ideal delivery modality should be able to incorporate large quantities of boron without affecting the selective delivery of the boron to the tumor. Small unilamellar liposomes encapsulating concentrated aqueous solutions of polyhedral borane salts and injected intravenously have been shown to deliver therapeutic quantities of boron selectively to tumors in vivo (4, 5). Although essentially any water-soluble boroncontaining compound can be encapsulated in the aqueous core of the liposomes and delivered to the tumor, only polyhedral borane salts that possess the potential to form covalent bonds with intracellular protein moieties have been retained in significant quantity by the tumor. Compounds that lack this chemical reactivity were cleared from all tissues, including tumor (4, 5). The necessity of liposomal incorporation for tumor accretion has been substantiated by the clearance of unincorporated (''free'') boron-containing compounds from all tissues, including tumor, in murine biodistribution experiments (4, 5).The polyhedral borane anions investigated for liposomal encapsulation have been based on the normal isomer of [B 20 H 18 ] 2Ϫ. Initial interest in this compound was derived from the large boron content per unit charge and the known susceptibility of the anion to nucleophilic attack. The anion is also synthesized in two high yield reactions, amenable to boron-10 enrichment, from decaborane, B 10 H 14 (6, 7).The substitution chemistry of the normal isomer of [B 20 H 18 ] 2Ϫ was first investigated by Hawthorne and coworkers (8,9). Nucleophilic attack on the electron-deficient threecenter two-electron bonds of [B 20 , w...

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Ein neuartiges Amidinium-verbrücktes polyedrisches Boran-Ion durch Einbau eines Acetonitrilmoleküls des Solvens

Shelly

Knobler

et al. 1998

Angewandte Chemie

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A Study of the Reaction of Hydroxide Ion with B₂₀H₁₈^-2

Cited by 29 publications

References 2 publications

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

Synthesis andin vivomurine evaluation of Na₄[1-(1′-B₁₀H₉)-6-SHB₁₀H₈] as a potential agent for boron neutron capture therapy

Ein neuartiges Amidinium-verbrücktes polyedrisches Boran-Ion durch Einbau eines Acetonitrilmoleküls des Solvens

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A Study of the Reaction of Hydroxide Ion with B20H18-2

Cited by 29 publications

References 2 publications

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

Synthesis andin vivomurine evaluation of Na4[1-(1′-B10H9)-6-SHB10H8] as a potential agent for boron neutron capture therapy

Ein neuartiges Amidinium-verbrücktes polyedrisches Boran-Ion durch Einbau eines Acetonitrilmoleküls des Solvens

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A Study of the Reaction of Hydroxide Ion with B₂₀H₁₈^-2

Synthesis andin vivomurine evaluation of Na₄[1-(1′-B₁₀H₉)-6-SHB₁₀H₈] as a potential agent for boron neutron capture therapy