New approaches to the functionalization of the 1-carba--decaborate anion.

Two new approaches to the functionalization of the 1-carba--decaborate anion [1-CBH] at boron atoms the ring-opening of its 1,4-dioxane derivative with various nucleophiles and Pd-catalysed cross-coupling of its iodo derivative with aromatic amines and heteroaromatics were developed.

Synthesis of 3-Aryl--carboranes with Sensitive Functional Groups.

A simple and efficient method was developed for the one-pot synthesis of 3-aryl derivatives of -carborane with sensitive functional groups using 3-iodo--carborane and aryl zinc bromides that were generated in situ. A series of 3-aryl--carboranes, including those containing nitrile and ester groups, 3-RCH-1,2-CBH (R = -Me, -NMe, -OCHOMe, -OMe, -CN, -CN, -COOEt, -COOEt, -COOEt) was synthesized using this approach. The solid-state structures of 3-RCH-1,2-CBH (R = -OMe, -CN, and -CN) were determined by single crystal X-ray diffraction.

The unexpected reactivity of 9-iodo-nido-carborane: from nucleophilic substitution reactions to the synthesis of tricobalt tris(dicarbollide) Na[4,4',4''-(MeOCHCHO)-3,3',3''-Co(μ-O)(μ-S)(1,2-CBH)].

An unusual reactivity of 9-iodo-nido-carborane [9-I-7,8-CBH] towards nucleophiles under strong basic conditions was revealed. The nucleophilic substitution of iodine with O- and N-nucleophiles results in [9-RO-7,8-CBH] (R = H, CHCHOMe) and [9-L-7,8-CBH] (L = Py, NEt, MeNCHCHNMe), respectively. Reaction of [9-I-7,8-CBH] with CoCl in 1,2-dimethoxyethane in the presence of t-BuOK, depending on the order of addition of the reagents, leads either to a diastereomeric mixture of diiodo derivatives cobalt bis(dicarbollide) rac-[4,4'-I-3,3'-Co(1,2-CBH)] and meso-[4,7'-I-3,3'-Co(1,2-CBH)] or to the corresponding mixture of 2-methoxyethoxy derivatives rac-[4,4'-(MeOCHCHO)-3,3'-Co(1,2-CBH)] and meso-[4,7'-(MeOCHCHO)-3,3'-Co(1,2-CBH)].

Effects of Linkers on the Development of Liposomal Formulation of Cholesterol Conjugated Cobalt Bis(dicarbollides).

Boron neutron capture therapy (BNCT) remains an important treatment arm for cancer patients with locally invasive malignant tumors. This therapy needs a significant amount of boron to deposit in cancer tissues selectively, sparing other healthy organs. Most of the liposomes contain water-soluble polyhedral boron salts stay in the core of the liposomes and have low encapsulation efficiency.

Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides.

A series of boron-containing lipids were prepared by reactions of cyclic oxonium derivatives of polyhedron boranes and metallacarboranes (closo-dodecaborate anion, cobalt and iron bis(dicarbollides)) with amine and carboxylic acids which are derived from cholesterol. Stable liposomal formulations, on the basis of synthesized boron-containing lipids, hydrogenated soybean l-α-phosphatidylcholine and (HSPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) as excipients, were prepared and then characterized by dynamic light scattering (DLS) that revealed the formation of particles to be smaller than 200 nm in diameter. The resulting liposomal formulations showed moderate to excellent loading and entrapment efficiency, thus justifying the design of the compounds to fit in the lipid bilayer and ensuring ease of in vivo use for future application.

Cyanide free contraction of disclosed 1,4-dioxane ring as a route to cobalt bis(dicarbollide) derivatives with short spacer between the boron cage and terminal functional group.

The 1,4-dioxane derivative of cobalt bis(dicarbollide) reacts with dialkylsulfides and triphenylphosphine to give the corresponding sulfonium and phosphonium derivatives [8-L(CH2CH2O)2-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)] (L = SMe2, S(CH2CH2)2O, PPh3). The treatment of the triphenylphosphonium derivative with sodium hydroxide results in contraction of the side chain with formation of [8-HOCH2CH2O-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)](-). The same product was obtained by treatment of the dimethylsulfonium derivative with the poorly nucleophilic base t-BuOK, whereas the stronger nucleophiles induce the sulfur demethylation to give [8-MeS(CH2CH2O)2-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)](-).