Non-spectator behavior of carborane ligands in icosahedral metallacarboranes

Icosahedral metallacarboranes with closo-3,1,2-MC₂B₉ frameworks are formally derived by η⁵ coordination of the open face of a nido-7,8-C₂B₉ cage to a metal atom. Recent work has established that the boron vertices of these faces readily form exo-polyhedral bonds of various kinds. These include linkages to other metal-ligand systems via either three-center two-electron B---H metal of two-center B-metal σ interactions, as well as attachments to organic groups with B---C or B---O bonds. Many new types of molecular structure have been identified, thereby opening a new domain of metallacarborane chemistry which merits further study.     

General method for the synthesis of 2′-O-carboranyl-nucleosides

The carboranyl cage is a new modifying entity for nucleosides, DNA oligonucleotides, and other biomolecules. Herein, the first reliable method for the synthesis of nucleosides modified with a carborane cluster at the 2′-position is described.     

Water-soluble phosphonium salts containing 1,12-dicarba-closo-dodecaborane(12)

The preparation of new water-soluble phosphonium salts containing 1,12-dodeca-closo-dodecaborane(12) (closo-1,12-carborane) for potential use as tumor-targeting agents in Boron Neutron Capture Therapy (BNCT) is described.     

Nucleoside-boron cluster conjugates - Beyond pyrimidine nucleosides and carboranes

General methods for the synthesis of new purine and pyrimidine nucleosides modified with borane clusters and metallacarborane complexes are presented. They include: (1) attachment of carborane modification at 2′ position of nucleoside via formacetal linkage formation, (2) tethering of the metallacarborane group at nucleobase part of the nucleoside via dioxane ring opening in oxonium metallacarborane, carborane or dodecaborate derivatives, and (3) ‘‘click” chemistry approach based on Huisgen 1,3-dipolar cycloaddition. Proposed methodologies extend the range of nucleoside-boron cluster conjugates available and open new areas for their applications.     

A new strategy for molecular modeling and receptor-based design of carborane containing compounds

Difficulties associated with computer-aided molecular design (CAMD) of carborane containing molecules have hampered drug development in boron neutron capture therapy (BNCT). A new approach of modeling and docking of carborane containing molecules with the readily available software packages , and is described. This new method is intended as a guide for boron chemists interested in using CAMD of carborane containing agents for medical applications such as BNCT.     

Magnesium-assisted intramolecular demethylation utilizing carborane C-H geometry

A novel type of demethylation reaction was designed in the Pd-catalyzed coupling reaction of iodocarboranes with several Grignard reagents, CH₃OPhMgBr. 3-Iodo-o-carborane 1 reacted with 2-CH₃OPhMgBr to afford the corresponding phenol compound 4b in 78% yield. However, when compound 1 was reacted with the other Grignard reagents, the corresponding methoxyl compounds 5a and 6a were obtained in excellent yields. 2-Iodo-p-carborane 3 reacted with 2-CH₃OPhMgBr to afford the corresponding phenol 8b in 50% yield and the methoxyl compound 8a in 41% yield. The carborane C-H geometry, which can form an intramolecular C-H?O hydrogen bonding, seems to be an important factor in the demethylation process. To examine the mechanism of the demethylation, compounds 1 and 4a were treated with CH₃MgBr and quenched with D₂O. While the two C-Hs of compound 1 were completely deuterated, compound 4a showed a replacement of one C-H with C-D. Therefore, we propose a mechanism involving intramolecular C-Mg?O interaction instead of intramolecular C-H?O interaction, via the generation of 3-iodo-o-carboranyl(MgBr)₂, 11. Since it is also possible to replace the C-Hs with various metals other than Mg, new applications of carboranes in coordination and metal catalyst chemistry can be expected.     

Metal complexes of monocarbon carboranes bearing C-amine or -amino substituents

Icosahedral metal-monocarbollide complexes in which the carbon atom of the {nido-CB₁₀} fragment carries an exo-polyhedral -NR₃ or -NR₂ group have an extensive chemistry. This is illustrated with complexes of ruthenium, osmium, rhodium, molybdenum, tungsten and rhenium. Many complexes with molecular structures new to the metallacarborane field have been discovered, and it has been shown that it is possible to introduce functional groups into the {nido-CB₁₀} cage system in many different ways.     

Synthesis of the first stable carborane containing simple enol

A carborane-containing stable simple enol — 1-2-isopropyl-o-carboran-I-yl)-1-phenyl2-mesityl-2-lrydroxyctlrylcne — has been synthesized. This enol does not isomerize to the starting ketone or keto-enol mixture even after prolonged heating in benzene in the presence of CF₃COOH.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1561–1563, June, 1996.     

Nido-carborane encapsulated by BODIPY zwitterionic polymers: Synthesis,photophysical properties and cell imaging

Carborane encapsulation was visualized by using fluoroboropyrrole (BODIPY) zwitterionic polymer as fluorescence marker. Firstly, a water-soluble fluorescent probe carrier was prepared by combining the BODIPY derivatives with poly (carboxybetaine methacrylate) (p-CBMA). Two oil-in-water carborane polymers were self-assembled in organic solvents by means of dual ion hydrogen bonding. The ultraviolet and fluorescence spectra were measured with different organic solvents, and the spectra ranged from 531 to 555 nm. The dynamic self-assembly effect was tested by TEM, and the internal microscopic phenomena of the water-soluble polymer were further observed. It was confirmed that two kinds of BODIPY zwitterionic polymers were firmly encase the fat-soluble carborane, forming an oval shape. Carboranes are water-soluble, can achieve biocompatible expression, and can visualize the degree of aggregation in the targeted cells through its own fluorescence effect. Subsequent imaging of the cells showed that both polymers entered the targeted cells.     

Novel carboranylporphyrins for application in boron neutron capture therapy (BNCT) of tumors

Condensation of a new carboranylpyrrole 1 with benzaldehydes leads to β-carboranylporphyrins 2 and 3 in good yields. These new porphyrins of high boron content (32-43%) have potential as boron delivery agents for BNCT. The X-ray structures of one β-carboranylporphyrin, of a carboranylpyrrole, and of a side-product are presented.     

Syntheses of C-substituted icosahedral dicarbaboranes bearing the 8-dioxane-cobalt bisdicarbollide moiety

The treatment of 1,2-, 1,7- and 1,12-carbaborane lithiated isomers with [3,3′-Co-8-(CH₂CH₂O)₂-(1,2-C₂B₉H₁₀)-(1′,2′-C₂B₉H₁₁)] (1) at molar ratios 1:1 or 1:2 at room temperature in THF leads generally to the formation of a series of orange double-cluster mono and dianions. These were characterized by NMR and MS methods as [1′′-X-1′′,2′′-closo-C₂B₁₀H₁₁]⁻, [2]⁻; [1′′-X-1′′,7′′-closo-C₂B₁₀H₁₁]⁻, [3]⁻ and [1′′-X-1′′,12′′-closo-C₂B₁₀H₁₁], [4]⁻ for the monoanions, whereas [1′′,2′′-X₂-1′′,2′′-closo-C₂B₁₀H₁₀]²⁻, [2]²⁻; [1′′,7′′-X₂-1′′,7′′-closo-C₂B₁₀H₁₀]²⁻, [3]²⁻; and [1′′,12′′-X₂-1′′,12′′-closo-C₂B₁₀H₁₀]²⁻, [4]²⁻ for the dianions (where X = 3,3′-Co-8-(CH₂CH₂O)₂-(1,2-C₂B₉H₁₀)-1′,2′-(C₂B₉H₁₁)). Moreover, these borane-cage subunits can be easily modified via attaching variable substituents onto cage carbon and boron vertices, which makes these compounds structurally flexible potential candidates for BNCT of cancer and HIV-PR inhibition.     

Synthesis,molecular structure and reactivity of the dimethyl sulfide adduct of a 1,3,2-diselenaborolane with an annelated dicarba-closo-dodecaborane(12) unit

The reaction of 1,2-diselenolato-1,2-dicarba-closo-dodecaborane(12) dianion [1,2-(1,2-C₂B₁₀H₁₀)Se₂]²⁻ with HBBr₂–SMe₂ affords the dimethyl sulfide adduct of 4,5-[1,2-dicarba-closo-dodecaborano(12)]-1,3-diselena-2-borolane in good yield. The molecular structure was determined by X-ray diffraction, and the solution-state structure was established by NMR spectroscopy (¹H, ¹¹B, ¹³C, ⁷⁷Se NMR). ¹¹B and ⁷⁷Se chemical shifts were reproduced by DFT calculations. Attempts were made to abstract dimethyl sulfide, and the parent donor-free compound could be detected in solution. The reactivity of the title compound was studied towards pyridine, Me₃SnF, [Pt(PPh₃)₂(C₂H₄)], tert-Bu-OH, AlMe₃ and AlH₃-N(Et)Me₂ as well as a hydroborating reagent.     

Synthesis of adenosine-based fluorosides containing a novel heterocyclic ring system

A novel class of fluorescent adenosine derivatives (fluorosides) containing the previously unreported 8-(3H-[1,2,3]triazol-4-yl)-9H-purine heterocyclic ring system is reported, with Sonogashira cross-coupling and [3+2]-cycloaddition reactions being the key steps in the synthesis.     

Synthesis of ether- and carbon-linked polycarboranyl porphyrin dimers for cancer therapies

Porphyrin dimers bearing multiple carborane cages for potential use as sensitizers in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) were synthesized from protoporphyrin dimethyl ester and characterized. Diastereomeric ether-linked dimers bearing four closo carborane cages (40 boron atoms) were found to be unstable to the acidic conditions necessary for conversion into water-soluble salts. In contrast, the carbon---carbon-linked dimers bearing six icosahedral carboranes (60 boron atoms) were stable to acid and could be isolated as water-soluble sodium salts. In vitro and in vivo studies of these novel molecules are currently under investigation.     

Synthesis,Structure, and Conformation of 2′,3′‐Fused Oxathiane and Thiomorpholine Uridines

The syntheses of two 2′,3′‐fused bicyclic nucleoside analogues, i.e., 1‐[(4aR,5R,7R,7aS)‐hexahydro‐5‐(hydroxymethyl)‐4,4‐dioxidofuro[3,4‐b][1,4]oxathiin‐7‐yl]pyrimidine‐2,4(1H,3H)‐dione ( 1a ) and 1‐[(4aS,5R,7R,7aS)‐hexahydro‐7‐(hydroxymethyl)‐1,1‐dioxido‐2H‐furo[3,4‐b][1,4]thiazin‐5‐yl]pyrimidine‐ 2,4(1H,3H)‐dione ( 1b ), are described, the key step being an intramolecular hetero‐Michael addition. Their structures and conformations, previously solved by X‐ray crystallography, were analyzed in more detail, using 1D‐ and 2D‐NMR as well as HR‐MS analyses.     

Synthesis and characterization of half-sandwich Rh, Ir complexes containing mono-thiolate-ortho-carborane ligand

Two binuclear complexes [Cp^∗M(Cl)Carb^S]₂ (Cp^∗ = η⁵-C₅Me₅, M = Rh (1a), Carb^S = SC₂(H)B₁₀H₁₀, Ir (1b)) were synthesized by the reaction of LiCarb^S with the dimeric metal complexes [Cp^∗MCl(μ-Cl)]₂ (M = Rh, Ir). Four mononuclear complexes Cp^∗M(Cl)(L)Carb^S (L = BuⁿPPh₂, M = Rh (2a), Ir (2b); L = PPh₃, M = Rh (4a), Ir (4b)) were synthesized by reactions of 1a or 1b with L (L = BuⁿPPh₂ (2); PPh₃ (4)) in moderate yields, respectively. Complexes 3a, 3b, 5a, 5b were obtained by treatment of 2a, 2b, 4a, 4b with AgPF₆ in high yields, respectively. All of these compounds were fully characterized by IR, NMR, and elemental analysis, and the crystal structures of 1a, 1b, 2a, 2b, 4a, 4b were also confirmed by X-ray crystallography. Their structures showed 3a, 3b and 5a, 5b could be expected as good candidates for heterolytic dihydrogen activation. Preliminary experiments on the dihydrogen activation driven by these half-sandwich Rh, Ir complexes were done under mild conditions.     

Nucleosides and nucleotides as potential therapeutic agents

The present article summarizes recent progress in the study of nucleoside derivatives as antiviral and immunosuppressive agents. A number of 5′-substituted 5′-deoxy nucleosides have been found to be permeable and nonincorporable antimetabolites of 5′-nucleotides. N⁶-isopentenyladenosine and analogs show certain promising immunosuppressive activities. Encouraged by the antibody-stimulating effect of oligonucleotides, we have developed a convenient synthesis of oligonucleotides using fully protected phosphorylated intermediates. A group of tetradeoxyribonucleotides, dApdApdApdX, was prepared for biological and physical evaluations. Nucleotide derivatives may prove valuable in the treatment of several immunological disorders.