New Azido Coumarins as Potential Agents for Fluorescent Labeling and Their "Click" Chemistry Reactions for the Conjugation with closo-Dodecaborate Anion.

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate derivative bearing terminal alkynyl group. CuI catalyzed Huisgen 1,3-dipolar cycloaddition reaction has led to fluorescent conjugates formation. The absorption-emission spectra of the formed conjugates have been presented. The antiproliferative activity and uptake of compounds against several human cell lines were evaluated.

Synthesis and Antibacterial Activity Studies of the Conjugates of Curcumin with closo-Dodecaborate and Cobalt Bis(Dicarbollide) Boron Clusters.

A series of novel conjugates of cobalt bis(dicarbollide) and closo-dodecaborate with curcumin were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition. These conjugates were tested for antibacterial activity. It was shown that all derivatives are active when exposed to Bacillus cereus ATCC 10702 and are not active against Gram-negative microorganisms and Candida albicans at the maximum studied concentration of 1000 mg/L. The conjugate of alkynyl-curcumin with azide synthesized from the tetrahydropyran derivative of cobalt bis(dicarbollide) exhibited activity against Gram-positive microorganisms: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and the clinical isolate MRSA 17, that surpassed curcumin by 2-4 times.

Synthesis and Structure of Nido-Carboranyl Azide and Its "Click" Reactions.

Novel zwitter-ionic nido-carboranyl azide 9-N3(CH2)3Me2N-nido-7,8-C2B9H11 was prepared by the reaction of 9-Cl(CH2)3Me2N-nido-7,8-C2B9H11 with NaN3. The solid-state molecular structure of nido-carboranyl azide was determined by single-crystal X-ray diffraction. 9-N3(CH2)3Me2N-nido-7,8-C2B9H11 was used for the copper(I)-catalyzed azide-alkyne cycloaddition with phenylacetylene, alkynyl-3ß-cholesterol and cobalt/iron bis(dicarbollide) terminal alkynes to form the target 1,2,3-triazoles. The nido-carborane-cholesterol conjugate 9-3ß-Chol-O(CH2)C-CH-N3(CH2)3Me2N-nido-7,8-C2B9H11 with charge-compensated group in a linker can be used as a precursor for preparation of liposomes for Boron Neutron Capture Therapy (BNCT). A series of novel zwitter-ionic boron-enriched cluster compounds bearing a 1,2,3-triazol-metallacarborane-carborane conjugated system was synthesized. Prepared conjugates contain a large amount of boron atom in the biomolecule and potentially can be used for BNCT.

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. The liposomal formulations based on cobalt and iron bis(dicarbollide)-based lipids were found to be nontoxic against both human breast normal epithelial cells MCF-10A and human breast cancer cells MCF-7.

Fast flip-flop of halogenated cobalt bis(dicarbollide) anion in a lipid bilayer membrane.

Transmembrane translocation (flip-flop) of cobalt bis(dicarbollide) (COSAN) anions, elicited by application of a voltage-jump across the lipid bilayer membrane, manifested itself in monoexponential electrical current transients in the microsecond time scale. Halogenation of COSAN led to multi-fold acceleration of the flip-flop, the effect increasing with the molecular weight of the halogens. The exception was a fluorinated analog which exhibited slowing of the translocation kinetics. Measurements of the fluorescence ratio of the dye di-4-ANEPPS in lipid vesicles showed significant differences in the adsorption of studied hydrophobic anions. Based on these data, it can be concluded that COSAN and COSAN-F2 were located on the surface of the lipid membrane in the cisoid conformation increasing the dipole potential of the lipid membrane, while other halogenated COSAN analogs were adsorbed in the transoid conformation. Differences in the flip-flop kinetics of COSAN analogs were attributed to variation in the molecular volume of the anions and their orientation on the membrane surface.

Nucleophilic addition reactions to nitrilium derivatives [B12H11NCCH3]- and [B12H11NCCH2CH3]-. Synthesis and structures of closo-dodecaborate-based iminols, amides and amidines.

The synthesis of the acetonitrilium and propionitrilium derivatives of closo-dodecaborate [B12H12]2- was discussed. The nucleophilic addition reactions of water, alcohols and secondary amines to the activated triple bond of the nitrilium derivatives yielded the corresponding iminols, imidates and amidines. The obtained results were supported by X-ray diffraction studies and DFT calculations.

Molecular conductors with a 8-hydroxy cobalt bis(dicarbollide) anion.

Molecular conductors based on the 8-hydroxy cobalt bis(dicarbollide) anion, (TMTTF)[8-HO-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)] (1), (BMDT-TTF)[8-HO-3,3'-Co(1,2-C2B9H10) (1',2'-C2B9H11)] (2), and (BEDT-TTF)[8-HO-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)] (3), were synthesized, and their crystal structures and electrical conductivities were determined. Compounds 2 and 3 are isostructural to the corresponding radical-cation salts of the parent cobalt bis(dicarbollide). All of the radical-cation salts prepared were found to be semiconductors. The relative stability of the rotation conformers of the [8-HO-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)](-) anion was estimated using DFT/BP86 quantum chemical calculations.

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. Thus, modifying the polyhedral boron core to make it hydrophobic and incorporating those into the lipid layer could be one of the ways to increase drug loading and encapsulation efficiency. Additionally, a systematic study about the linker-dependent effect on drug encapsulation and drug-release is lacking, particularly for the liposomal formulation of hydrophobic-drugs. To achieve these goals, liposomal formulations of a series of lipid functionalized cobalt bis(dicarbollide) compounds have been prepared, with the linkers of different hydrophobicity. Hydrophobicity of the linkers have been evaluated through logP calculation and its effect on drug encapsulation and release have been investigated. The liposomes have shown high drug loading, excellent encapsulation efficiency, stability, and non-toxic behavior. Release experiment showed minimal release of drug from liposomes in phosphate buffer, ensuring some amount of drug, associated with liposomes, can be available to tumor tissues for Boron Neutron Capture Therapy.

Synthesis and the structure of 8-tetrahydrofuronium and 8-tetrahydropyronium derivatives of iron bis(dicarbollide)(-I) and their cleavage reactions.

8-Tetrahydrofuronium and 8-tetrahydropyronium derivatives of iron bis(dicarbollide)(-I) were synthesized. Their reactions of ring cleavage by MeOH, N3(-), amines and 1,2-bis(diphenylphosphino)ethane were investigated. 8-Tetrahydrofuronium iron bis(dicarbollide)(-I) was found to be more active in these reactions in comparison with 8-tetrahydropyronium and 8-dioxonium species, respectively. The first conjugates of iron bis(1,2-dicarbollide)(-I) with 2'-deoxyadenosine modified via the C-8 position of the purine base were synthesized. Reactions of these oxonium compounds with 1,2-bis(diphenylphosphino)ethane (dppe) led to zwitter-ionic monophosphonium salts. One of these compounds has given rise to a novel ferracarborane/cobaltacarborane hybrid complex.