New Boron Containing Acridines: Synthesis and Preliminary Biological Study.

The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with NCHCHNH, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles.

New Azido Coumarins as Potential Agents for Fluorescent Labeling and Their "Click" Chemistry Reactions for the Conjugation with -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 -dodecaborate derivative bearing terminal alkynyl group.

Boron-Cluster Embedded Necklace-Shaped Nanohoops.

The combination of carbon-based nanohoops with other functional organic molecular structures should lead to the design of new molecular configurations with interesting properties. Here, necklace-like nanohoops embedded with carborane were synthesized for the first time. The unique deboronization of o-carborane has led to the facile preparation of ionic nanohoop compounds.

Synthesis of Cobalt Bis(Dicarbollide)-Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy.

A series of novel cobalt bis(dicarbollide)-curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained.

Palladium-Catalyzed Hydroboration of Alkynes with Carboranes: Facile Construction of a Library of Boron Cluster-Based AIE-Active Luminogens.

The classical aggregation-induced emission (AIE)-active luminogens (AIEgens) usually include two-dimensional aromatic systems such as tetraphenylethenes, which are synthesized in several steps by using toxic additives. Here, we proposed a new molecular design strategy for the realization of AIE properties by combining three-dimensional aromatic boron clusters of carboranes with vinyl group(s). To obtain a library of the boron cluster-based AIEgens, a Pd-catalyzed hydroboration of alkynes with carboranes is reported.

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

A series of novel conjugates of cobalt bis(dicarbollide) and -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 ATCC 10702 and are not active against Gram-negative microorganisms and at the maximum studied concentration of 1000 mg/L.

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

The synthesis of the acetonitrilium and propionitrilium derivatives of -dodecaborate [BH] 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.

Highly Purified Conjugates of Natural Chlorin with Cobalt Bis(dicarbollide) Nanoclusters for PDT and BNCT Therapy of Cancer.

To combine the neutron-capturing and photodynamic properties of boron nanoclusters and derivatives of natural chlorins, respectively, in one molecule, conjugate of chlorin e6 methyl ester with cyclen and dioxane and nitrile derivatives of cobalt bis(dicarbollide) were synthesized. The conditions for the purification of compounds by HPLC were selected since the work with natural compounds is complicated by the production of closely related impurities.

Synthesis of Zwitter-Ionic Conjugate of -Carborane with Cholesterol.

9-HC≡CCHMeN--7,8-CBH, a previously described carboranyl terminal alkyne, was used for the copper(I)-catalyzed azide-alkyne cycloaddition with azido-3β-cholesterol to form a novel zwitter-ionic conjugate of -carborane with cholesterol, bearing a 1,2,3-triazol fragment. The conjugate of -carborane with cholesterol, containing a charge-compensated group in the linker, can be used as a precursor for the preparation of liposomes for BNCT (Boron Neutron Capture Therapy). The solid-state molecular structure of a -carborane derivative with the 9-MeN(CH)MeN--7,8-CBH terminal dimethylamino group was determined by single-crystal X-ray diffraction.

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide).

A series of novel cobalt bis(dicarbollide) based amidines were synthesized by the nucleophilic addition of primary and secondary amines to highly activated B-N≡C-R triple bond of the propionitrilium derivative [8-EtC≡N-3,3'-Co(1,2-CBH)(1',2'-CBH)]. The reactions with primary amines result in the formation of mixtures of and isomers of amidines, whereas the reactions with secondary amines lead selectively to the -isomers. The crystal molecular structures of -[8-EtC(NMe)=HN-3,3'-Co(1,2-CBH)(1',2'-CBH)], -[8-EtC(NEt)=HN-3,3'-Co(1,2- CBH)(1',2'-CBH)] and -[8-EtC(NCH)=HN-3,3'-Co(1,2-CBH)(1',2'-CBH)] were determined by single crystal X-ray diffraction.

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

Novel zwitter-ionic -carboranyl azide 9-N(CH)MeN--7,8-CBH was prepared by the reaction of 9-Cl(CH)MeN--7,8-CBH with NaN. The solid-state molecular structure of -carboranyl azide was determined by single-crystal X-ray diffraction. 9-N(CH)MeN--7,8-CBH was used for the copper(I)-catalyzed azide-alkyne cycloaddition with phenylacetylene, alkynyl-3β-cholesterol and cobalt/iron bis(dicarbollide) terminal alkynes to form the target 1,2,3-triazoles.

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.

Conjugate of chlorin with iron bis(dicarbollide) nanocluster: synthesis and biological properties.

Efficiency of both photodynamic and boron-neutron capture anticancer therapies (BNCT) depends on the properties of the used photo- and neutronsensitizer. We report on the synthesis and properties of the advanced photo- and neutronsensitizer designed as a conjugate of chlorin with iron bis(dicarbollide) nanocluster. The conjugate is shown to accumulate efficiently in rat glioblastoma C6 cells delivering >10 boron atoms per cell and thus meeting requirements for BNCT agents, to provide photoinduced 50% death of C6 cells at 35 ± 3 nM, to be not toxic for cells without activating stimulus.

Small-sized gadolinium oxide based nanoparticles for high-efficiency theranostics of orthotopic glioblastoma.

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size.

Synthesis and study of -substituted methylthio derivatives of cobalt bis(dicarbollide).

The -methylthio derivatives of cobalt bis(dicarbollide) were synthesized by reaction of anhydrous CoCl with -carborane [7-MeS-7,8-CBH] and isolated as a mixture of -[1,1'-(MeS)-3,3'-Co(1,2-CBH)] and -[1,2'-(MeS)-3,3'-Co(1,2-CBH)] isomers. The structures of both isomers were studied using DFT quantum chemical calculations. The most preferable geometry of rotamers and the stabilization energy of -methylthio derivatives of cobalt bis(dicarbolide) were calculated.

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors.

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.

Pharmacokinetics of Chlorin e₆-Cobalt Bis(Dicarbollide) Conjugate in Balb/c Mice with Engrafted Carcinoma.

The necessary precondition for efficient boron neutron capture therapy (BNCT) is control over the content of isotope B in the tumor and normal tissues. In the case of boron-containing porphyrins, the fluorescent part of molecule can be used for quantitative assessment of the boron content. We performed a study of the biodistribution of the chlorin ₆-Cobalt bis(dicarbollide) conjugate in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and developed a mathematical model describing boron accumulation and release based on the obtained experimental data.

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.

Carborane Derivative Conjugated with Gold Nanoclusters for Targeted Cancer Cell Imaging.

Polyhedral borane derivatives have been utilized in the treatment of boron neuron capture therapy (BNCT) for brain glioma, and much attention has been paid to search excellent biocompatible boron-rich composites for effective cancer BNCT therapy. In this study, we have exploited the self-assembly of the gold nanoclusters with carborane amino derivatives (GNCs-CB) for the precise bioimaging of cancer cells and targeted delivery of this carborane compound to the tumors. Our observations demonstrate that the GNCs-CB can readily realize accurate tumor imaging and long-term accumulation in tumor sites by EPR effect and nanometer size effect, and thus efficiently implement tumor-targeting delivery of the carborane derivative and facilitate the real-time fluorescent visualization monitoring of the carborane targeted delivery process.

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)](-).

Tungsten carbonyl σ-complexes with charge-compensated nido-carboranyl thioether ligands.

Charge-compensated nido-carboranyl thioether ligands [7-MeS-10-Me2S-7,8-C2B9H10] and [7,8-(MeS)2-10-Me2S-7,8-C2B9H9] were prepared and fully characterized. They readily react with labile tungsten carbonyls to give σ-complexes - mono-substituted (CO)5W[7-MeS-10-Me2S-7,8-C2B9H10-κ(1)-S(1)] and (CO)5W[7,8-(MeS)2-10-Me2S-7,8-C2B9H9-κ(1)-S(1)] and chelate (CO)4W[7,8-(MeS)2-10-Me2S-7,8-C2B9H9-κ(2)-S(1),S(2)]. The synthesized metallocomplexes were characterized by multinuclear NMR spectroscopy and single crystal X-ray diffraction.

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.

A new approach to the synthesis of functional derivatives of nido-carborane: alkylation of [9-MeS-nido-7,8-C2B9H11]⁻.

A series of asymmetrically substituted sulfonium derivatives of nido-carborane [9-R(Me)S-nido-7,8-C2B9H11] (R = Et, Pr, Bu, Bn, CH=CH2, CH2CH=CH2, CH2C≡CH, CH=C=CH2) were prepared by alkylation of the 9-methylthio-nido-7,8-carborane. The synthesized compounds are the first examples of diastereomers combining nido-carborane and sulfonium chiral centers.