The design and synthesis of icosahedral polyhedral borane closomer motifs based upon carbonate and carbamate anchoring groups for biomedical applications are described. Dodecacarbamate closomers ...containing easily accessible groups of interest at their linker termini were synthesized via activation of the B–OH vertices as aryl carbonates and their subsequent reaction with primary amines. Novel dodecacarbonate closomers were successfully synthesized for the first time by reacting closo-B12(OH)122– with an excess of respective aryl chloroformates, utilizing relatively short reaction times, mild conditions and simple purification strategies, all of which had previously presented difficulties in closomer chemistry. This methodology for the 12-fold degenerate synthesis of carbonate and carbamate closomers will greatly facilitate further exploration of closomers as monodisperse nanomolecular delivery platforms.
Twelve of one, a dozen of the other: Synthetic pseudometallic molecules were prepared by fully substituting the B12H122− ion with 12 alkoxy groups. Reversible redox reactions reveal ...substituent‐dependent potentials varying over 1.2 V (see picture) which were characterized and correlated using Hammett and QSAR linear free‐energy relationships.
Clusters with a click: The chemistry of icosahedral borane closomers has been combined with click chemistry for the first time. This approach provided a facile syntheses of diverse 12‐fold closomer ...nanoparticles (see scheme; R=alkyl or aryl) which could be adapted for biomedical and material applications.
This report addresses the incidence of vascular endothelial cell apoptosis in the mouse small intestine in relation to the radiation-induced gastrointestinal (GI) syndrome.
Nonanesthetized mice ...received whole-body irradiation at doses above and below the threshold for death from the GI syndrome with 250 kVp X-rays, (137)Cs gamma rays, epithermal neutrons alone, or a unique approach for selective vascular irradiation using epithermal neutrons in combination with boronated liposomes that are restricted to the blood. Both terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining for apoptosis and dual-fluorescence staining for apoptosis and endothelial cells were carried out in jejunal cross-sections at 4 h postirradiation.
Most apoptotic cells were in the crypt epithelium. The number of TUNEL-positive nuclei per villus was low (1.62 +/- 0.03, mean +/- SEM) for all irradiation modalities and showed no dose-response as a function of blood vessel dose, even as the dose crossed the threshold for death from the GI syndrome. Dual-fluorescence staining for apoptosis and endothelial cells verified the TUNEL results and identified the apoptotic nuclei in the villi as CD45-positive leukocytes.
These data do not support the hypothesis that vascular endothelial cell apoptosis is the cause of the GI syndrome.
The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received ...wholebody epithermal neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min⁻¹. An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 μm) particles released from neutron capture reactions in$^{10}B$confined to the blood by incorporation into liposomes 70-90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g$^{10}B$in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min⁻¹, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific wholebody neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.
Unique nanosized closomers of high boron content that may exhibit potential as boron neutron capture therapy target species have been synthesized. The design of these boron-rich nanospheres is based ...in part on previous work involving dodeca(carboranyl)-substituted closomers Thomas, J.; Hawthorne, M. F. Chem. Commun. 2001, 1884−1885. Coupling of ortho-carborane moieties through ester and ether linkages to the rigid closo-B12(OH)122- scaffold resulted in the development of a 12(12)-closomer−ester derivative, dodeca6-(1,2-dicarba-closo-dodecaboran-1-yl)hexanoate-closo-dodecaborate (2−), 6, and 12(12)-closomer−ether derivatives, dodeca6-(2-methy1-1,2-dicarba-nido-dodecaboran-1-yl)hexyl-closo-dodecaborane (14−), 14, and dodeca6-(7,8-dicarba-nido-dodecaboran-7-yl)hexyl-closo-dodecaborane (14−), 15. These closomers were investigated by UV−visible spectroscopy and cyclic voltammetry. Additionally, a deboronation method employing NaCN as the nucleophilic reagent was utilized to obtain sodium salts of the ether-linked nido-closomer polyanions, which were purified using a newly developed size-exclusion high pressure liquid chromatography method.
The scope and limitations of the alkylation of closo-B12(OH)122- using a series of fourteen alkyl and aralkyl halides and two p-toluenesulfonic acid esters in the presence of ...N,N-diisopropylethylamine have been investigated. The dodecaalkoxy-closo-dodecaborate products, closo-B12(OR)122-, and their hypercloso two-electron oxidation products have been explored. The species closo-B12(OR)122- containing 26 cage-bonding electrons may undergo two reversible, sequential, one-electron oxidation processes, producing a 25-electron radical anion and a 24-electron neutral species. Several oxidizing reagents were investigated for the chemical oxidation of closo-B12(OR)122- and hypercloso-B12(OR)12- to hypercloso-B12(OR)12. Both FeCl3 . 6H2O and K3Fe(CN)6 in 90/5/5 ethanol/acetonitrile/H2O were found to be the reagents of choice. The reverse reaction leading from the neutral species to the radical anion and subsequently to the dianion was achieved using sodium borohydride in ethanol. A variety of alkoxyl derivatives have been synthesized by heating the reactants for extended periods of time in acetonitrile at the reflux temperature. The use of elevated reaction temperatures attained by employing moderate argon pressure (autoclave) over the reaction mixture led to drastic reductions in reaction times and increased efficiency. X-ray diffraction studies of substituted dodecabenzyl ether derivatives proved that 2 2- has approximate I h symmetry while hypercloso-2, -3, -9, -11, -12, and -13 have approximate D 3 d point group symmetry due to Jahn−Teller distortion from I h .
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