V. I. Bregadze

Polyhedral boron compounds as potential diagnostic and therapeutic antitumor agents.

The use of polyhedral boron hydrides for cancer treatment is traditionally connected with boron neutron capture therapy. More recently, polyhedral borate anions were proposed as carriers of radionuclide label for targeted radionuclide therapy and diagnostics of cancer. Some metal derivatives of carboranes were found to demonstrate significant antitumor activity themselves. This review is designed to highlight the recent work concerning various fields of potential application of polyhedral boron compounds in anticancer diagnostics and therapy.

Cyclic oxonium derivatives of polyhedral boron hydrides and their synthetic applications.

Cyclic oxonium derivatives of polyhedral boron hydrides are a relatively new class of boron compounds. They have great potential for the modification of various types of organic and bioorganic molecules and the synthesis of compounds that could be used in different fields from the treatment of nuclear wastes to the treatment of cancer. In the present Perspective we would like to present an overview of the results of the preparation and synthetic application of these compounds.

Synthesis of functional derivatives of the [3,3′-Co(1,2-C2B9H11)2]− anion

Abstract A series of various functional derivatives of the cobalt bis(1,2-dicarbollide) anion [8-XCH2CH2OCH2CH2O-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)]− (X=OH, NH2, and CH(NH2)COOH) were prepared by the ring-opening reactions of [8-O(CH2CH2)2O-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)] with different nucleophiles followed by functional group interconversion reactions. Acidic hydrolysis of [8-NCCH2CH2OCH2CH2O-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)]− resulted in the shorter-chain alcohol [8-HOCH2CH2O-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)]−. Structures of (Bu4N)[8-AcNHC(COOEt)2CH2CH2OCH2CH2O-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)] and [8-(1-C5H5N)CH2CH2OCH2CH2O-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)] were determined by the single crystal X-ray diffraction method. Perspectives of application of functionalized cobalt bis(1,2-dicarbolide) derivatives in nuclear medicine are discussed.

Synthesis of oxonium derivatives of the dodecahydro-closo-dodecaborate anion [B12H12]2−. Tetramethylene oxonium derivative of [B12H12]2− as a convenient precursor for the synthesis of functional compounds for boron neutron capture therapy

Direct synthesis of oxonium derivatives of the dodecahydro-closo-dodecaborate anion is described and the reaction mechanism is discussed. Various derivatives of the [B12H12](2-) anion containing hydroxyl, amine, acid, and amino acid functions were prepare

Derivatives of the closo-dodecaborate anion and their application in medicine

The paper presents a comparative analysis of the possibilities and characteristic features of the application of various polyhedral boron compounds, viz., the closo-decaborate anion [B10H10]2–, the closo-dodecaborate anion [B12H12]2–, the carba-closo-dodecaborate anion [CB11H12]–, carboranes C2B10H12, and the bis(dicarbollide) complexes [M(C2B9H11)2]– (M = Fe, Co, or Ni), in boron neutron capture therapy (BNCT) for cancer. The requirements on compounds used in BNCT are formulated and the advantages of the application of the closo-dodecaborate anion are considered. The data on the synthesis of various derivatives of the closo-dodecaborate anion, which either already found use in BNCT or are most promising in this field, are summarized. The possibilities of the application of agents derived from the closo-dodecaborate anion in medical diagnostics are discussed.

Ligand effects in the hydrogenation of methacycline to doxycycline and epi-doxycycline catalysed by rhodium complexes. Molecular structure of the key catalyst [closo-3,3-(η2,3-C7H7CH2)-3,1,2-Rh C2B9H11]

Abstract The catalytic reduction of the exocyclic methylene group of methacycline (A) leads to the formation of two diastereoisomers, doxycycline (B, the α-epimer) and 6-epi-doxycycline (C, the β-epimer), with a selectivity which markedly depends on the nature of hydrocarbon and carborane ligands of closo-(π-cyclodienyl)rhodacarborane catalysts. Neutral norbornadienyl complexes with unsubstituted carborane ligands [closo-3,3-(η2,3-C7H7CH2)-3,1,2-RhC2B9H11] (1) and [closo-2,2-(η2,3-C7H7CH2)-2,1,7-RhC2B9H11] (7) are more active and afford higher selectivity in the formation of doxycycline than those having mono- or di-substituents at the carborane cage, [closo-3,3-(cyclodienyl)-1-R-2-R′-3,1,2-RhC2B9H9] (R = H, R′ = Me, PhCH2; R = R′ = Me; cyclodienyl = η2,3-C7H7CH2 or η-C10H13) as well as those from the closely related series of η5-cyclopentadienyl complexes [(η2,3-C7H7CH2)Rh(η5-C5Rn)]+PF6− (Rn = H5, Me5, or H2-1,2,4-Ph3). Mechanistic aspects of the hydrogenation reaction of methacycline are sketched. The results of the X-ray diffraction study of the best catalyst 1 are reported.

Chemistry of nickel and iron bis(dicarbollides). A review

Abstract Synthesis and chemical properties of nickel and iron bis(dicarbollides) and their derivatives are reviewed. A review with 81 references.

Synthesis and derivatization of the 2-amino-closo-decaborate anion [2-B10H9NH3]-

Abstract A novel high-yield method of synthesis of the [2-B10H9NH3]− anion was elaborated. The method proposed includes reaction of the closo-decaborate anion with acetonitrile in the presence of acid, followed by hydrolysis of the formed nitrilium derivative [2-B10H9NCMe]− first to the acetamide derivative [2-B10H9NH2COMe]− and then to the amine. The crystal molecular structure of (Bu4N)[2-B10H9NHC(OH)Me] was determined by single crystal X-ray diffraction method. In the solid state, the acetamide derivative exists in the O-protonated tautomeric form and has a Z-configuration where the NH proton and the OH group are trans around the CN bond. The reaction of the [2-B10H9NH3]− anion with aromatic aldehydes in methanol in the presence of catalytic amounts of alkali gives N-protonated Schiff bases [2-B10H9NHCHR]− (R=C6H5, C6H4-2-OMe, C6H4-4-NHCOMe). Reduction of the Schiff bases with NaBH4 in aqueous methanol gives the corresponding monoalkylamino derivatives [2-B10H9NH2CH2R]− (R=C6H5, C6H4-2-OMe, C6H4-4-NHCOMe). The approach developed can be used in the synthesis of functional derivatives of the closo-decaborate anion for applications in nuclear medicine.

Stepwise and selective carborane substitution in the B(3,6) positions of a 16e CpCo half-sandwich complex containing a chelating ortho-carborane-1,2-dithiolate ligand.

The reactions of the 16e half-sandwich complex, CpCo(S(2)C(2)B(10)H(10)) (1), with alkynones at ambient temperature lead to complexes CpCo(S(2)C(2)B(10)H(9))(CH=CH-C(O)R) (R = Ph (2), 2-naphthyl (3)). Both 2 and 3 are still 16e half-sandwich complexes containing a B(3)-substituted ortho-carborane-1,2-dithiolate ligand. Treatment of 2 with excess alkynes R(1)C[triple bond]CR(2) (R(1) = H, R(2) = Ph, C(O)Ph, CO(2)Me; R(1) = R(2) = CO(2)Me) affords five complexes, CpCo(S(2)C(2)B(10)H(8))(CH(2)CPh)(CH=CH-C(O)Ph) (4), CpCo(S(2)C(2)B(10)H(8))(CH=CH-C(O)Ph)(2) (5), CpCo(S(2)C(2)B(10)H(8))(CH=CH-CO(2)Me)(CH=CH-C(O)Ph) (6), CpCo(S(2)C(2)B(10)H(9))(MeO(2)C-C=C-CO(2)Me)(CH=CH-C(O)Ph) (7), and CpCo(S(2)C(2)B(10)H(9))(MeO(2)C-C=C-CO(2)Me)(2)(CH=CH-C(O)Ph) (8). Complex 4 is an 18e complex bearing a B-CH(2) unit. Both 5 and 6 retain a 16e half-sandwich structure but contain a B(3,6)-disubstituted ortho-carborane-1,2-dithiolate ligand. However, in 7 and 8 one or two alkynes are inserted into one of the Co-S bonds to generate 18e species, respectively. Heating 7 leads to the 16e complex, CpCo(S(2)C(2)B(10)H(8))(MeO(2)C-C=CH-CO(2)Me)(CH=CH-C(O)Ph) (9), having a B(3,6)-disubstituted ortho-carborane-1,2-dithiolate ligand as in 5 and 6. All complexes were fully characterized by spectroscopic techniques and elemental analysis. The solid-state structures of 2 and 3 and 5-9 were further characterized by X-ray structural analysis.

Synthesis of alkoxy derivatives of dodecahydro-closo-dodecaborate anion [B12H12]2−

Dodecahydro-closo-dodecaborate anion [B12H12](2-) is a stable non-toxic highly water-soluble boron-rich compound. Functionalized derivatives of this compound are of high interest as BNCT agents. Th ...