The Preparation and Rearrangement of the Three Isomeric B20H18-4 Ions

The polyhedral borane ion [n-B2,HlaJs reacts with liquid ammonia in the presence of a suitable base to produce an apical-equatorial (ae) Isomer of the [B, [1][2])-2-NHIE3BIep3. The structure of this product has been confire by "B NMR c opy and x-ray c lgraphy. This spe undergoes acid-catalyzed rearrangement to an apical-apical (ae) isomer, [1-(1'-B1JHI)-2-NHI3BJhs]P-, whose structure has been determined by "1B NMR spectroscopy. The Successful application of BNCT depends on the identification of boron compounds, such as boron-conjugated porphyrins (2), that possess a natural mechanism for tumor cell accretion or, alternatively, a tumor-specific delivery modality through which compounds rich in boron may be specifically delivered to tumor cells. The use of tumor-specific delivery modalities, such as tumor-targeted monoclonal antibody conjugates, has thus far been limited by the highly competitive loss of conjugate to liver once therapeutically effective amounts of boron have been conjugated to the antibody (3).The ideal delivery mechanism should be able to incorporate large quantities of boron without affecting its selective delivery of 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).

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“…The reaction of NH2, generated in situ, with [n-B2oHis]2-in liquid NH3 produces [ (10) and the unsubstituted, [B20H18]4-, series (14). Fig.…”

Section: Resultsmentioning

confidence: 99%

Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.

Feakes

Shelly

Knobler

et al. 1994

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

121

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“…The reduction of n-B20H2 by mild reducing agents (18) produces B20H18, which in aqueous solution is in equilibrium with the protonated species B2oHI-. Biodistribution experiments with the sodium salt of this anion demonstrated that although the tumor-boron level is steadily reduced with time, the concentration at 48 h is still 11.2 pug/g because of the very high initial uptake (27.7 Ag at 6 h).…”

Section: Resultsmentioning

confidence: 99%

“…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.

153

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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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“…The calculated natural populations are listed in Table 3 14 where the very large downfield shift of 11.9 ppm corresponds to the position of the biggest electronic density. As a result, 11.19 (s, 2B) should be the large downfield shift of two ''oa'' boron atoms.…”

Section: Natural Populationsmentioning

confidence: 99%

Ab initio studies on isomers of macropolyhedral borane ions [B₂₀H₁₈]ⁿ (n = 0, –2, –4)

Zhang

Zhao

et al. 2006

J Comput Chem

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Various isomers of macropolyhedral borane ions [B20H18]n (n = 0, -2, -4) are investigated by using the density functional theory methods at RB3LYP/6-31+G* and RB3LYP/6-31G* levels to obtain the optimized geometries, harmonic vibrational frequencies, electron structures, and the stability order. The calculated results show that optimized bond lengths are consistent with the available experimental values and the natural populations, taking [a2 -B20H18]4- (4) as an example, are also in agreement with NMR spectra. The calculated vibrational frequencies are all real, so all of these isomers could be stable, among which [a2 -B20H18]2- (3) and [a2 -B20H18]0 (7) are considered for the first time in this paper. On the basis of the contour maps of molecular orbitals, the delocalized characteristic of molecular orbitals and the possible redox mechanism of these ions are also discussed. Moreover, the analysis on counting of skeletal bonding electrons shows that the isomers (1)-(6) obey the electronic requirement predicted by the mno rule, whereas the newly predicted isomer (7) does not match the mno rule.

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The Preparation and Rearrangement of the Three Isomeric B₂₀H₁₈^-4 Ions

Cited by 65 publications

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Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.

Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.

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

Ab initio studies on isomers of macropolyhedral borane ions [B₂₀H₁₈]ⁿ (n = 0, –2, –4)

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The Preparation and Rearrangement of the Three Isomeric B20H18-4 Ions

Cited by 65 publications

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Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.

Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.

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

Ab initio studies on isomers of macropolyhedral borane ions [B20H18]n (n = 0, –2, –4)

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The Preparation and Rearrangement of the Three Isomeric B₂₀H₁₈^-4 Ions

Ab initio studies on isomers of macropolyhedral borane ions [B₂₀H₁₈]ⁿ (n = 0, –2, –4)