Polyhedral Borane Anions Research Articles

NITROGEN HETEROCYCLIC SALTS OF POLYHEDRAL BORANE ANIONS: FROM IONIC LIQUIDS TO ENERGETIC MATERIALS

Synthesis, structure, and physical properties of nitrogen heterocyclic salts of the polyhedral borane anions (closo-decaborate [B 10 H 10 ] 2– , closo-dodecaborate [B 12 H 12 ] 2– , carba-closo-dodecaborate [CB 11 H 12 ] – , and 3,3'-cobaltabis(1,2-dicarbollide) [3,3'-Co(1,2-C 2 B 9 H 11 ) 2 ] – ) and their derivatives, including their potential application as ionic liquids and energetic materials, are reviewed. Author: Igor B. Sivaev

Nitrogen heterocyclic salts of polyhedral borane anions: from ionic liquids to energetic materials

Synthesis, structure, and physical properties of nitrogen heterocyclic salts of the polyhedral borane anions (closo-decaborate [B10H10]2–, closo-dodecaborate [B12H12]2–, carba-closo-dodecaborate [CB11H12]–, and 3,3'-cobaltabis(1,2-dicarbollide) [3,3'-Co(1,2-C2B9H11)2]–) and their derivatives, including their potential application as ionic liquids and energetic materials, are reviewed.

Evaluation of the binding of polyhedral borane anions to representative proteins

The ability of three polyhedral borane anions, [B20H18]2−, [B20H17SH]4−, and [B20H19]3−, to bind to proteins was evaluated by measuring the total boron content using inductively coupled plasma-atomic emission spectroscopy after purification by gel electrophoresis. Results were correlated to the known chemical reactivity of the compounds as well as the reported murine biodistributions of the liposomally encapsulated sodium salts of each of the polyhedral borane anions. Qualitative reactions were performed with the [B20H18]2− anion to determine the potential reactivity with simple molecular building blocks.

Facile synthesis and regeneration of Mg(BH4)2by high energy reactive ball milling of MgB2

We report direct hydrogenation of MgB(2) in a planetary ball mill. Magnesium borohydride, Mg(BH(4))(2), and various polyhedral borane anion salts have been synthesized at pressures between 50 and 350 bar H(2) without the need for subsequent isothermal hydrogenation at elevated temperature and pressure. The obtained products release ∼4 wt% H(2) below 390 °C, and a major portion of Mg(BH(4))(2) transforms back to MgB(2) at around 300 °C, demonstrating the possibility of reversible hydrogen storage in an Mg(BH(4))(2)-MgB(2) system.

Synthesis and Investigation of [B20H17O(CH2)5]3–, a Novel Solvent Complex of the [B20H18]4–Ion

Reaction of the [trans-B(20)H(18)](2-) ion with the n-butoxide ion, formed in situ from reaction of n-butanol and NaH, in tetrahydropyran (THP) produces in good yield an unexpected and isolable solvent-coordinated polyhedral borane anion, [ae-B(20)H(17)O(CH(2))(5)](3-). The anticipated product of nucleophilic attack, [ae-B(20)H(17)On-Bu](4-), is not observed under the reaction conditions. The solvent-coordinated product is also formed in the presence of either ethoxide or carbamate ion but is not observed if the ethoxide or carbamate ion is not present in stoichiometric amounts. In the presence of the n-butanethiol anion, the coordinated THP ring undergoes a ring-opening reaction, yielding the [ae-B(20)H(17)O(CH(2))(5)Sn-Bu](4-) anion. Ring opening is also observed in the presence of the ethoxide ion in refluxing THP. Isolation of the previously proposed analogous solvent-coordinated tetrahydrofuran (THF) product, [ae-B(20)H(17)O(CH(2))(4)](3-), was unsuccessful; however, the product resulting from ring opening of THF by the n-butanethiol anion is reported.

Catalytic hydroxylation of [Closo-B12H12]2−—adaptation of the Periana reaction to a polyhedral borane

Per-B-hydroxylation of a polyhedral borane anion has been demonstrated by the catalytic hydroxylation of icosahedral [closo-B(12)H(12)](2-) using soft electrophiles such as platinum group metal catalysts or iodine cation. A new route to [closo-B(12)(OH)(12)](2-) from [closo-B(12)H(12)](2-) without the use of H(2)O(2) oxidant provides an alternative hydroxylation process.

ADVANCES AT THE INTERFACE OF POLYHEDRAL BORANE CHEMISTRY AND MEDICINE

I first met Gordon during the autumn of 1960 when we were both located at Harvard. Gordon was an Assistant Professor of Inorganic Chemistry while I was on temporary appointment as a Visiting Lecturer teaching Paul Bartlett's graduate course on organic chemistry. My stay at Harvard was made possible by a leave of absence from the Rohm and Haas Company, Redstone Arsenal Research Division. Gordon's research at the time was concerned with the study of the NMR phenomena associated with the acid-base complexes of boranes and Lewis bases. He was just beginning to enter the emerging field of modern organometallic chemistry. My interests at that time, and since, were centered upon the exploratory chemistry of the larger boranes, polyhedral borane anions and the carboranes. I had not yet discovered metallacarborane chemistry, an event of 1965. Both Gordon and I interacted scientifically with Bill Lipscomb during our time at Harvard. This was a truly exciting era since Lipscomb was developing his bonding theory for boranes and rapidly determining the structures of a variety of borane derivatives made available by the research community. Early in 1961 I returned to my industrial position and in 1962 I became a Professor of Chemistry at the University of California, Riverside. Gordon returned to England as a Professor of Inorganic Chemistry at Queen Mary College, the University of London. Later, Gordon became a Professor of Inorganic Chemistry at the University of Bristol with astounding success. Throughout the years Gordon has always provided me with invitations to participate in important scientific meetings and lectures in Britain. The first instance in which Gordon entertained me occurred in 1963 when he arranged my appointment as a special lecturer at the University of London and several other universities. The number of invitations which Gordon has extended to me over the years is too large to recall, but I shall always be grateful for his friendship and help extended to me in the earliest part of my career. Consequently, I am extremely grateful for the opportunity to attend this meeting in Waco and to interact with my old friend, Gordon Stone. I wish him well even though he insists upon drawing dicarbollide-containing structures “upside-down”!

ChemInform Abstract: Theoretical Aspects of Metal Cluster Chemistry

During the last twenty years the Polyhedral Skeletal Electron Pair Theory and the isolobal analogy have provided a theoretical basis for the rapid experimental developments, which have occurred in metal cluster chemistry. These theoretical principles have been underpinned by m.o. calculations on specific molecules and more generally by the Tensor Surface Harmonic Theory. This paper will review the important theoretical developments and relate them to the experimental and structural data which have been obtained for cluster compounds in our own and other laboratories. In particular the application of theoretical principles for rationalising and predicting the structures of cluster compounds of the platinum metals and gold are discussed. The bonding requirements of interstitial atoms and fragments are discussed, particularly in the context of interstitial C, B, N and transition metal atoms and diatomic fragments, e.g. C2 and C-H. POLYHEDRAL SKELETAL ELECTRON PAIR THEORY The historical development of the theoretical ideas which have contributed to the Polyhedral Skeletal Electron Pair Theory can be traced back to the pioneering work of Longuet-Higgins forty years ago. In the 1950's the contributions of Longuet-Higgins proved decisive since he not only provided a molecular orbital description of the bonding in diborane (ref. l), but also pioneered the application of molecular orbital theory ideas to deltahedral borides and boranes (ref. 2). The three-centre two-electron description of B-H-B and B-B-B bonds was elegantly generalised into the styx formalism and applied to all known boron hydrides by Lipscomb (ref. 3). The molecular orbital analysis of polyhedral boranes resulted in the successful prediction of the octahedral and icosahedral borane anions some years before they were structurally characterised (ref. 4). Hoffmann and Lipscomb (ref. 5) also developed the molecular orbital methodology of L nguet-Higgins in a general molecular orbital analysis of polyhedral borane anions, BnH;-, in 1962. In the 1960's Cotton and Haas (ref. 6) pioneered the development of molecular orbital ideas to metal cluster compounds of the early transition metals stabilised by halide ligands. Their analysis emphasised the important interactions which can result in such clusters from the overlap of the transition metal d orbitals. An alternative localised description of the bonding in such clusters, which resembled the styx methodology, was proposed by Kettle (ref. 7). These theoretical models tended to emphasise the inherent differences between metal and main group clusters and in common with ligand field theory tended to stress the role of the metal d orbitals. By the mid-nineteen sixties the major classes of transition metal IT -donor and acceptor clusters, and main group polyhedral borane and Zintl 'naked' clusters had been established but were viewed as distinct areas of inorganic chemistry. Experimental studies had, however, begun to indicate the artificiality of these subdivisions. The synthesis of polyhedral organometallic compounds from the reactions of acetylenes with metal carbonyls by HUbel and Braye and transition metallocarboranes by Hawthorne's group (ref. 8) clearly demonstrated that it was possible to synthesise polyhedral molecules with transition metal and main group atoms at the vertices. In addition the structural characterisation of Rh6(C0Il6 by Dahl (ref. 9) provided a real difficulty for the theoretical models which were most widely used. The bonding in Rh6(C0)16 could not be explained by the effective atomic number rule and was not amenable to a molecular orb'tal

Boron‐Containing Protoporphyrin IX Derivatives and Their Modification for Boron Neutron Capture Therapy: Synthesis, Characterization, and Comparative In Vitro Toxicity Evaluation

A novel series of boronated porphyrins for potential use in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) for tumor suppression is described. Protoporphyrin IX {i.e., bis(alpha-methyl-beta-pentylethylether)protoporphyrin IX, and bis(alpha-methyl-beta-dodecanylethylether)protoporphyrin IX} bearing polyhedral borane anions (B(12)H(11)SH(2-), B(12)H(11)NH(3) (-), or B(12)H(11)OH(2-)) were synthesized with reasonable yields. Modification of the protoporphyrin IX structure was achieved by variation of the lengths of the alkyl chains (pentyl and dodecanyl) attached through ether linkages to the former vinyl groups. The goal of this modification was to develop boronated porphyrins with chemical and physical properties that differed from those of protoporphyrin IX. Performance of an MTT assay with each derivative revealed that the synthesized boronated porphyrins showed low cytotoxicities in a variety of cancer cells. Of these compounds, B(12)H(11)NH(2) (2-)-conjugated porphyrin induced a significant increase in the level of boron accumulation and PDT efficacy against HeLa cells.

Investigation of the Interactions of Polyhedral Borane Anions with Serum Albumins

Boron neutron capture therapy (BNCT) is a type of radiation therapy used in the treatment of cancerous tumors such as gliboblastoma multiforme and metastatic melanoma. BNCT is dependent on the site specific delivery and retention of boron‐10 atoms within the tumor. The ability of polyhedral borane anions to form covalent bonds with biochemical macromolecules appears to be critical for boron retention within the tumor cell. The polyhedral borane anions [B20H17OH]4−, [B20H18]2−, and [B20H17SH]4− were allowed to react with serum albumins, and the reaction products were investigated using polyacrylamide gel electrophoresis (Native‐PAGE), matrix assisted laser desorption ionization time of fight (MALDI‐TOF), electrospray ionization and nuclear magnetic resonance (NMR). The formation of disulfide linkage between [B20H17SH]4− and the free cysteine residue in the albumin was observed while [B20H17OH]4− and [B20H18]2− showed no evidence of covalent bonding. The understanding of covalent binding of polyhedral borane anions will aid in the synthesis and design of agents used in BNCT.

Investigation of the interactions of polyhedral borane anions with serum albumins

The retention of polyhedral borane anions within tumor cells has been attributed to the possible formation of covalent bonds with nucleophilic protein substituents. In an effort to identify the nature of possible interactions between polyhedral borane anions and proteins, three polyhedral borane anions, [B20H18]2−, [B20H17OH]4−, and [B20H17SH]4−, were allowed to react with either bovine or human serum albumin. Reaction products were analyzed with matrix assisted laser desorption ionization (MALDI) mass spectrometry and gel electrophoresis. Evidence of disulfide bond formation was observed with the [B20H17SH]4− anion, whereas no evidence of covalent binding was observed with the [B20H18]2− and [B20H17OH]4− ions. The potential for disulfide bond formation was confirmed by examining the reactions of the [B20H17SH]4− ion with both DTNB and reduced glutathione. An understanding of the nature of the binding will provide a basis for the design and synthesis of boron-containing compounds for application in boron neutron capture therapy.

Synthesis and Comparative Toxicology of a Series of Polyhedral Borane Anion-Substituted Tetraphenyl Porphyrins

Three structurally similar tetraphenylporphyrins bearing polyhedral borane anions have been synthesized and their toxicological profiles obtained in rats. These conjugates were found to have quite different acute toxicities as manifested at the maximum tolerated dose (MTD). When given at the MTD and observed over 28 days, the most acutely toxic porphyrin was found to be devoid of toxicity, as measured by blood chemistry panels. The remaining two less acutely toxic compounds both elicited significant changes, characterized by moderate to severe thrombocytopenia, failure to gain weight normally and changes in liver enzymes indicative of mild hepatotoxicity. All toxic effects were transient, with platelets rebounding to above normal levels at day 28. We conclude that thrombocytopenia is the dose limiting toxicity for boronated porphyrins in mammals and suggest that these effects may be due to the porphyrin, not the borane or carborane.

Carbonium ion salts. Part 16. Molecular orbital study of tropylium ions with borane anion and carborane substituents (hemiousene compounds)

We have extended our ab initio study of substituted tropylium ions to examine several known and postulated hemiousene compounds where the ring has a substituent derived from a polyhedral borane anion, carborane, or carborane anion. Tropyliumyl derivatives of the borane anions closo-B 10H 10 2−, closo-B 12H 12 2−, and closo-CB 9H 10 − are Type III substituted tropylium ions with substituent to ring charge-transfer in the HOMO–LUMO (HL) transition. An additional boron electron pair of the closo-cage in 2-C 7H 6–B 10H 9 − and C 7H 6–B 12H 11 − is completely delocalized over cage and ring. Tropyliumyl derivates of the carborane and carborane anions closo-C 2B 10H 12 and closo-CB 11H 12 − are Type II substituted tropylium ions with polarization of ring π-system by substituent and little if any charge-transfer HL interaction. The tropyliumyl derivative of nido-C 2B 9H 12 − is in a class by itself; however both theory and experiment demonstrate that it has strong HL charge-transfer like a Type III ion.

Synthesis and in vivo murine evaluation of Na4[1-(1'-B10H9)-6-SHB10H8] as a potential agent for boron neutron capture therapy.

Reaction of the normal isomer of [B20H18]2- and the protected thiol anion, [SC(O)OC(CH3)3]-, produces an unexpected isomer of [B20H17SC(O)OC(CH3)3]4- directly and in good yield. The isomer produced under mild conditions is characterized by an apical-apical boron atom intercage connection as well as the location of the thiol substituent on an equatorial belt adjacent to the terminal boron apex. Although the formation of this isomer from nucleophilic attack of the normal isomer of [B20H18]2- has not been reported previously, the isomeric assignment has been unambiguously confirmed by one-dimensional and two-dimensional 11B NMR spectroscopy. Deprotection of the thiol substituent under acidic conditions produces a protonated intermediate, [B20H18SH]3-, which can be deprotonated with a suitable base to yield the desired product, [B20H17SH]4-. The sodium salt of the resulting [B20H17SH]4- ion has been encapsulated in small, unilamellar liposomes, which are capable of delivering their contents selectively to tumors in vivo, and investigated as a potential agent for boron neutron capture therapy. The biodistribution of boron was determined after intravenous injection of the liposomal suspension into BALB/c mice bearing EMT6 mammary adenocarcinoma. At low injected doses, the tumor boron concentration increased throughout the time-course experiment, resulting in a maximum observed boron concentration of 46.7 micrograms of B per g of tumor at 48 h and a tumor to blood boron ratio of 7.7. The boron concentration obtained in the tumor corresponds to 22.2% injected dose (i.d.) per g of tissue, a value analogous to the most promising polyhedral borane anions investigated for liposomal delivery and subsequent application in boron neutron capture therapy.

Synthesis of Alkyl and Aryl Derivatives of closo-B12H122- by the Palladium-Catalyzed Coupling of closo-B12H11I2- with Grignard Reagents

The reaction of [N(n-C4H9)4]2[closo-B12H11I], [N(n-Bu)4]2[2], with Grignard reagents, RMgX, in the presence of catalytic amounts of trans-Pd(PPh3)2Cl2 and CuI in either tetrahydrofuran or 1,4-dioxane solution produced the corresponding alkylated or arylated polyhedral borane anions, closo-B12H11R2-, in good yield. By this method, we have synthesized [N(n-C4H9)4]2[closo-B12H11CH3], [N(n-Bu)4]2[3]; [N(n-C4H9)4]2[closo-B12H11C6H5], [N(n-Bu)4]2[4]; and Cs2[closo-B12H11(n-C18H37)], Cs2[5]. The structures of Cs2[3] and PPN2[4] have been determined by X-ray diffraction studies. Crystallographic data are as follows: for Cs2[3], orthorhombic, space group Pmcn, a = 954.6(6) pm, b = 1077.0(7) pm, c = 1396.8(9) pm, Z = 4, R = 0.055; for PPN2[4], which cocrystallized with two molecules of DMSO and one molecule of toluene, triclinic, space group P1̄, a = 1138.4(10) pm, b = 1920.1(17) pm, c = 2143.2(18) pm, α = 93.26(2)°, β = 104.44(2)°, γ = 105.86(2)°, Z = 2, R = 0.076.

An Exploratory Evaluation of the Reactions of Organic Oxidants with Polyhedral Borane Anions

The possible utilization of organic oxidizing agents in polyhedral borane anion redox chemistry was examined by using the synthesis of the well-characterized [B20H18]2- anion as a model system. The...

Synthesis and Structure of the Polyhedral [μ-B20H17OH]2- Borane Anion Containing Both Oxygen- and Hydrogen-Bridge Bonds

We report here the synthesis, structure, and reactions of the oxygen and hydrogen doubly bridged polyhedral borane anion [{mu}-B{sub 20}H{sub 17}-OH]{sup 2-} (4). A demonstration of the facile alkylation of 4 is provided by heating the {mu}-B{sub 20}H{sub 17}2{sup 3-} ion with ethyl iodide in MeCN to produce 3 ([{mu}-B{sub 20}H{sub 17}OC{sub 2}H{sub 5}]{sup 2-}) in 88% yield. The efficacious alkylation reaction of this oxygen-bridged polyhedral borane anion provides a route to oxygen-substituted species. The derivatization of 4 with organic substrates will lead to a variety of derivatives having potential utility in BNCT. We are continuing the exploration of this novel chemistry. 15 refs., 1 fig.

Synthesis of Amine Derivatives of the Polyhedral Borane Anion [B(20)H(18)](4)(-).

Ethylenediamine (en) reacts with the polyhedral borane anion [n-B(20)H(18)](2)(-), in the presence or absence of strong nonnucleophilic auxiliary bases, to produce the [ae-B(20)H(17)(en)](3)(-) anion. In either case, substitution is accompanied, to an approximately equal extent, by reduction of the starting material to form [a(2)()-B(20)H(18)](4)(-). As found with similar substituted systems derived from this 20-boron structure, [ae-B(20)H(17)(en)](3)(-) may be conveniently rearranged to the [a(2)()-B(20)H(17)(en)](3)(-) anion. A more convenient synthesis of the known [ae-B(20)H(17)NH(3)](3)(-) ion, which employs acetonitrile as the source of the NH(3) ligand instead of liquid ammonia, is also described.

Synthesis and Structure of the Elusive [a2-B20H19]3- Anion

The apical-apical isomer of the polyhedral borane anion [a{sup 2}-B{sub 20}H{sub 18}]{sup 4{minus}} reacts with various proton sources in dichloromethane to produce the protonated species [a{sup 2}-B{sub 20}H{sub 19}]{sup 3{minus}} in high yield. The mixed tetraethylammonium-pyridinium salt of [a{sup 2}-B{sub 20}H{sub 19}]{sup 3{minus}} crystallizes in the monoclinic space group P2{sub 1}/n with a = 11.223(3) {angstrom}, b = 10.970(3) {angstrom}, c = 15.328(4) {angstrom}, {beta} = 106.06(1){degrees}, V = 1819 {angstrom}{sup 3}, and Z = 2. Data were collected on a Syntex P1 diffractometer using Cu K{alpha} radiation, to a maximum 2{theta} = 115{degrees}, giving 2359 unique reflections, and the structure was solved by direct methods (SHELX86). The final discrepancy indices were R = 0.062 and R{sub w} = 0.086 for 1967 independent reflections with I > 3{sigma}(I). The structure of the [a{sup 2}-B{sub 20}H{sub 19}]{sup 3{minus}} anion is similar to that of its apical-apical [a{sup 2}-B{sub 20}H{sub 18}]{sup 4{minus}} precursor with the addition of a hydrogen bridge connecting the two 10-boron atom cages. The boron-hydrogen-boron bond forms an angle of 91(3){degrees} although the component B{sub 10}H{sub 9} cages a share a common axis through their B(1)-B(10) vertices.

Bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low energy (< or = 0.025 eV) or thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. A major requirement for the success of BNCT is the selective delivery of a sufficient number of boron atoms (approximately 10(9)) to individual cancer cells to sustain a lethal 10B (n, alpha) 7Li capture reaction. A panel of BsAb reactive with polyhedral borane anions (PBA) and a tumor-associated chondroitin sulfate proteoglycan has been produced. All of these BsAb showed strong reactivity with a panel of human glioblastoma and melanoma cell lines, as demonstrated by indirect membrane immunofluorescence. Two of them (H6 and B8) also reacted with cells that had been exposed to PBA (Na2B10H10 and Na2B12H11SH) and a boronated starburst dendrimer, which contained approximately 250-400 B atoms per molecule. The affinity constant (Ka) of BsAb-B8 was 2.57 x 10(8) M-1 on M21 human melanoma cell and 3.49 x 10(8) M-1 on A172 glioblastoma cells, which were almost identical to those of the parental monoclonal antibody (mAb) 9.2.27 on the same cell lines (2.62 x 10(8) M-1). Since our BsAb recognize both human glioblastoma and melanoma-associated antigens, as well as PBA, they potentially could be used to target 10B to these tumors for BNCT.