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A multimeric MRI blood pool contrast agent based on the closo-borane motif is reported. Twelve copies of an amphiphilic DTPA chelate with amine end groups are appended on carbonate-functionalized closo-borane motif using carbamate linkages. The presence of peripheral phenyl groups on the modified DTPA chelates results in high human serum albumin binding, high relaxivity, and excellent contrast enhancement in vitro and in vivo.

Two approaches for the synthesis of rodlike polymers having metal bis(dicarbollide) anions connected by organic linkers, such as acetylene and 1,4-dibutyl-2,5-diethynylbenzene, in the backbone are reported. Route 1 involved connecting nido-bis(carborane) compounds, containing the linkers, via π coordination with Co or Ni metals. This reaction yielded small oligomers having one to six repeating units. Route 2 utilized a palladium-catalyzed cross-coupling copolymerization of diiodo-substituted cobaltocarboranes and a zinc-derivatized aromatic linker. This approach gave a mixture of oligomers and polymers. The polymers were separated from the smaller oligomers by dialysis and were characterized by 1H NMR, 11B NMR, 11B{1H} NMR, IR, UV–vis, TEM, and AFM techniques. End-group analysis and dynamic-light scattering experiments (DLS) determined that the average number of repeating units in the polymers ranged between 35 and 44. GPC analyses failed to aid the molecular weight determination due to the adsorption of ...

The thermal decompositions of metallaisoxazolin-5-ones containing Ir, Rh, or Co are investigated using density functional theory. The experimentally observed decarboxylations of these molecules are found to proceed through retro-(3+2)-cycloaddition reactions, generating the experimentally reported η2 side-bonded nitrile complexes. These intermediates can isomerize in situ to yield a η1 nitrile complex. A competitive alternative pathway is also found where the decarboxylation happens concertedly with an aryl migration process, producing a η1 isonitrile complex. Despite their comparable stability, these η1 bonded species were not detected experimentally. The experimentally detected η2 side bound species are likely involved in the subsequent C–H activation reactions with hydrocarbon solvents reported for some of these metallaisoxazolin-5-ones.

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9)-2-NH3B10H8] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. Despite relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.

This review is dedicated to a relatively new, but nevertheless very quickly evolving field of chemistry - closomer chemistry. Closomers are complex organoelement molecules built on a [B12]2- icosahedral platform that have the combined benefits of the symmetry and stability of polyhedral boranes and the diversity of organic chemistry. On a material level, closomers can be considered as monodisperse molecular nanoparticles because of their size, spherical symmetry, and ease of adjusting the arm length. The ease of twelvefold side-chain functionalization and the possibility of heterosubstitution makes closomers very useful medical tools for targeted and traceable imaging and drug delivery applications.

The reactions between low-valent Rh(I) and Ir(I) metal-carbonyl complexes and arylnitrile oxides possess the electronic and structural features of 1,3-dipolar cycloadditions. Density functional theory (DFT) calculations on these reactions, involving both cyclopentadienyl and carboranyl ligands on the metal carbonyl, explain the ease of the chemical processes and the stabilities of the resulting metallaisoxazolin-5-ones. The metal-carbonyl bond has partial double bond character according to the Wiberg index calculated through NBO analysis, and so the reaction can be considered a normal 1,3-dipolar cycloaddition involving M═C bonds. The rates of formation of the metallacycloadducts are controlled by distortion energy, analogous to their organic counterparts. The superior ability of anionic Ir complexes to share their electron density and accommodate higher oxidation states explains their calculated higher reactivity toward cycloaddition, as compared to Rh analogues.

We synthesized a family of neuromuscular blocking agents (NMB) based on decamethonium, but containing a carborane cluster in the methylene chain between the two quaternary ammonium groups. The carborane cluster isomers o-NMB, m-NMB, and p-NMB were tested in animals for neuromuscular block and compared with agents used clinically: rocuronium and decamethonium. All three isomers caused reversible muscle weakness in mice as determined by grip strength and inverted screen tests, with a potency rank of p-NMB > rocuronium > decamethonium > m-NMB > o-NMB. The mechanism of action of the compounds was determined by using the in vitro rat phrenic nerve hemi-diaphragm preparation and electrophysiologic measurements in cells. Neostigmine reversed hemi-diaphragm weakness caused by the three isomers and rocuronium, but not succinylcholine. In electrophysiologic recordings of currents through acetylcholine receptor channels, the carborane compounds did not activate channel activity but did inhibit channel activation by acetylcholine. These results demonstrate that the carborane neuromuscular blocking agents are non-depolarizers in contrast to the depolarizing action of the parent compound.

The construction and application of a unique monodisperse closomer drug-delivery system (CDDS) integrating three different functionalities onto an icosahedral closo-dodecaborane [B12 ](2-) scaffold is described. Eleven B-OH vertices of [closo-B12 (OH)12 ](2-) were used to attach eleven copies of the anticancer drug chlorambucil and the targeting vector glucosamine through a bifurcating lysine linker. The remaining twelfth vertex was used to attach a fluorescent imaging probe. The presence of multiple glucosamine units offered a monodisperse and highly water-soluble CDDS with a high payload of therapeutic cargo. This array enhanced the penetration of the drug into cancer cells by exploiting the overexpression of GLUT-1 receptors present on cancer cells. About 15-fold enhancement in cytotoxicity was observed for CDDS-1 against Jurkat cells, compared to CDDS-2, which lacks the GLUT-1 targeting glucosamine. A cytotoxicity comparison of CDDS-1 against colorectal RKO cells and its GLUT-1 knock-out version confirmed that GLUT-1 mediates endocytosis. Using fluorescent markers both CDDS-1 and -2 were traced to the mitochondria, a novel target for alkylating agents.

Four mixed-ligand bis(dicarbollyl)nickel(IV) complexes 4b-e were prepared in good yields via a two-step procedure including (1) ligand exchange reactions between the nickelacarborane complex 3,3-(PPh3)2-closo-3,1,2-NiC2B9H11 (1) and the appropriate substituted dicarbollide-dianions generated from the TBA-salts of nido-carborane anions [7,8-C2B9H11(R)]− {R = 3-[(CH2)5C16H9] (2b); 5-[m-CF3C6H4] (2c); 5-[p-CH3OC6H4] (2d); and 1-[C≡CTIPS] (2e)} in THF and (2) subsequent oxidation of the prepared paramagnetic intermediate Ni(III) complexes 3b-e by FeCl3 in acetonitrile. Target compounds were characterized using a combination of spectroscopic techniques. The structure of 4e was determined using X-ray diffraction.