Towards the Application of Purely Inorganic Icosahedral Boron Clusters in Emerging Nanomedicine.

Traditionally, drugs were obtained by extraction from medicinal plants, but more recently also by organic synthesis. Today, medicinal chemistry continues to focus on organic compounds and the majority of commercially available drugs are organic molecules, which can incorporate nitrogen, oxygen, and halogens, as well as carbon and hydrogen. Aromatic organic compounds that play important roles in biochemistry find numerous applications ranging from drug delivery to nanotechnology or biomarkers. We achieved a major accomplishment by demonstrating experimentally/theoretically that boranes, carboranes, as well as metallabis(dicarbollides), exhibit global 3D aromaticity. Based on the stability-aromaticity relationship, as well as on the progress made in the synthesis of derivatized clusters, we have opened up new applications of boron icosahedral clusters as key components in the field of novel healthcare materials. In this brief review, we present the results obtained at the Laboratory of Inorganic Materials and Catalysis (LMI) of the Institut de Ciència de Materials de Barcelona (ICMAB-CSIC) with icosahedral boron clusters. These 3D geometric shape clusters, the semi-metallic nature of boron and the presence of exo-cluster hydrogen atoms that can interact with biomolecules through non-covalent hydrogen and dihydrogen bonds, play a key role in endowing these compounds with unique properties in largely unexplored (bio)materials.

Reversibly Switchable Fluorescent Molecular Systems Based on Metallacarborane-Perylenediimide Conjugates.

Icosahedral metallacarboranes are θ-shaped anionic molecules in which two icosahedra share one vertex that is a metal center. The most remarkable of these compounds is the anionic cobalt-based metallacarborane [Co(C2 B9 H11 )2 ]- , whose oxidation-reduction processes occur via an outer sphere electron process. This, along with its low density negative charge, makes [Co(C2 B9 H11 )2 ]- very appealing to participate in electron-transfer processes. In this work, [Co(C2 B9 H11 )2 ]- is tethered to a perylenediimide dye to produce the first examples of switchable luminescent molecules and materials based on metallacarboranes. In particular, the electronic communication of [Co(C2 B9 H11 )2 ]- with the appended chromophore unit in these compounds can be regulated upon application of redox stimuli, which allows the reversible modulation of the emitted fluorescence. As such, they behave as electrochemically-controlled fluorescent molecular switches in solution, which surpass the performance of previous systems based on conjugates of perylendiimides with ferrocene. Remarkably, they can form gels by treatment with appropriate mixtures of organic solvents, which result from the self-assembly of the cobaltabisdicarbollide-perylendiimide conjugates into 1D nanostructures. The interplay between dye π-stacking and metallacarborane electronic and steric interactions ultimately governs the supramolecular arrangement in these materials, which for one of the compounds prepared allows preserving the luminescent behavior in the gel state.

Tuning the Cell Uptake and Subcellular Distribution in BODIPY-Carboranyl Dyads: An Experimental and Theoretical Study.

A set of BODIPY-carboranyl dyads synthesized by a Sonogashira cross-coupling reaction, where different C-substituted ortho- and meta-carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and single XRD experiments, optical absorption/emission studies and partition coefficient (log P) measurements. These studies, supported by DFT computations (M06-2X/6-31G**), provide an explanation to the largely divergent cell income that these fluorescent carboranyl-based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m-carboranyl-BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o-carborane, suggesting that m-isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for boron neutron capture therapy.

Blue Emitting Star-Shaped and Octasilsesquioxane-Based Polyanions Bearing Boron Clusters. Photophysical and Thermal Properties.

High boron content systems were prepared by the peripheral functionalisation of 1,3,5-triphenylbenzene (TPB) and octavinylsilsesquioxane (OVS) with two different anionic boron clusters: closo-dodecaborate (B12) and cobaltabisdicarbollide (COSAN). TPB was successfully decorated with three cluster units by an oxonium ring-opening reaction, while OVS was bonded to eight clusters by catalysed metathesis cross-coupling. The resulting compounds were spectroscopically characterised, and their solution-state photophysical properties analysed. For TPB, the presence of COSAN dramatically quenches the fluorescence emission (λem = 369 nm; ΦF = 0.8%), while B12-substituted TPB shows an appreciable emission efficiency (λem = 394 nm; ΦF = 12.8%). For octasilsesquioxanes, the presence of either COSAN or B12 seems to be responsible for ∼80 nm bathochromic shift with respect to the core emission, but both cases show low emission fluorescence (ΦF = 1.4-1.8%). In addition, a remarkable improvement of the thermal stability of OVS was observed after its functionalisation with these boron clusters.

Fluorescent BODIPY-Anionic Boron Cluster Conjugates as Potential Agents for Cell Tracking.

A series of novel fluorescent BODIPY-anionic boron cluster conjugates bearing [B12H12]2- (5, 6), [3,3'-Co(1,2-C2B9H11)2]- (7, 8), and [3,3'-Fe(1,2-C2B9H11)2]- (9) anions have been readily synthesized from meso-(4-hydroxyphenyl)-4,4-difluoro-4-bora-3 a,4 a-diaza- s-indacene (BODIPY 4), and their structure and photoluminescence properties have been assessed. Linking anionic boron clusters to the BODIPY (4) does not alter significantly the luminescent properties of the final fluorophores, showing all of them similar emission fluorescent quantum yields (3-6%). Moreover, the cytotoxicity and cellular uptake of compounds 5-9 have been analyzed in vitro at different concentrations of B (5, 50, and 100 µg B/mL) using HeLa cells. At the lowest concentration, none of the compounds shows cytotoxicity and they are successfully internalized by the cells, especially compounds 7 and 8, which exhibit a strong cytoplasmic stain indicating an excellent internalization efficiency. To the best of our knowledge, these are the first BODIPY-anionic boron cluster conjugates developed as fluorescent dyes aiming at prospective biomedical applications. Furthermore, the cellular permeability of the starting BODIPY (4) was improved after the functionalization with boron clusters. The exceptional cellular uptake and intracellular boron release, together with the fluorescent and biocompatibility properties, make compounds 7 and 8 good candidates for in vitro cell tracking.

Carborane-BODIPY Dyads: New Photoluminescent Materials through an Efficient Heck Coupling.

A small library of carborane-BODIPY/aza-BODIPY dyads were efficiently synthesized by means of a novel convergent synthetic approach, the key step of which is a Pd-catalyzed Heck coupling reaction. The structural characterization and photoluminescence properties of the newly synthesized dyads were evaluated. The presence of the carborane did not significantly alter the photophysical patterns of the BODIPY or aza-BODIPY in the final fluorophores, but it produced a decrease of the emission fluorescent quantum yields that was in the range from 1.4 % for aza-BODIPY to 48 % for BODIPY-dyads. The carborane-BODIPY dyads were successfully incorporated into cells, especially compounds 2, 4 and 13, demonstrating their cytoplasmic localization. The fluorescent and biocompatibility properties make these compounds good candidates for in vitro cell tracking.

Organotin Dyes Bearing Anionic Boron Clusters as Cell-Staining Fluorescent Probes.

Within the cell nucleus, in the nucleoli, ribosomal RNAs are synthesized and participate in several biological processes. To better understand nucleoli-related processes, their visualization is often required, for which specific markers are needed. Herein, we report the design of novel fluorescent organotin compounds derived from 4-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide and their cytoplasm and nucleoli staining of B16F10 cells in vitro. Tin compounds bearing an aliphatic carbon chain (-C12 H25 ) and an electron-donating group (-OH) were prepared, and the latter could be derivatized to bear the boron cluster anions [B12 H12 ]2- and [3,3'-Co(1,2-C2 B9 H11 )2 ]- (COSAN). All of the conjugates have been fully characterized and their luminescence properties have been assessed. In general, they show good quantum yields in solution (24-49 %), those for the COSAN derivatives being lower. Remarkably, the linking of [B12 H12 ]2- and COSAN to the complexes made them more soluble, without being detrimental to their luminescence properties. Living B16F10 cells were treated with all of the compounds to determine their fluorescence staining properties; the compounds bearing the aliphatic chain showed a reduced staining capacity due to the formation of aggregates. Notably, the complexes bearing different boron clusters showed different staining effects; those bearing [B12 H12 ]2- showed extraordinary staining of the nucleoli and cytoplasm, whereas those bearing COSAN were only detected in the cytoplasm. The remarkable fluorescence staining properties shown by these organotin compounds make them excellent candidates for fluorescence bioimaging in vitro.

Electrochemistry and Photoluminescence of Icosahedral Carboranes, Boranes, Metallacarboranes, and Their Derivatives.

Icosahedral boranes, carboranes, and metallacarboranes are extraordinarily robust compounds with desirable properties such as thermal and redox stability, chemical inertness, low nucleophilicity, and high hydrophobicity, making them attractive for several applications such as medicine, nanomaterials, molecular electronics, energy, catalysis, environmental chemistry, and other areas. The hydrogen atoms in these clusters can be replaced by convenient groups that open the way to a chemical alternative to conventional "organic" or "organometallic" realms. Icosahedral boron cluster derivatives have been reviewed from different perspectives; however, there is a need for a review dedicated to the redox and photophysical characteristics of easily accessible borane and carborane derivatives, which are excellent materials for a wide range of applications. This review deals with the redox properties and photoluminescence behavior of this collection of compounds, as well as their influence on the properties of materials and devices whose working principles are related to electron-transfer or electron-promotion phenomena. We hope that this review will be of great value to boron cluster scientists and researchers working in the photoluminescence and electrochemistry fields who are interested in exploring the possibilities of these unique and promising systems.

Monolayer Contact Doping from a Silicon Oxide Source Substrate.

Monolayer contact doping (MLCD) is a modification of the monolayer doping (MLD) technique that involves monolayer formation of a dopant-containing adsorbate on a source substrate. This source substrate is subsequently brought into contact with the target substrate, upon which the dopant is driven into the target substrate by thermal annealing. Here, we report a modified MLCD process, in which we replace the commonly used Si source substrate by a thermally oxidized substrate with a 100 nm thick silicon oxide layer, functionalized with a monolayer of a dopant-containing silane. The thermal oxide potentially provides a better capping effect and effectively prevents the dopants from diffusing back into the source substrate. The use of easily accessible and processable silane monolayers provides access to a general and modifiable process for the introduction of dopants on the source substrate. As a proof of concept, a boron-rich carboranyl-alkoxysilane was used here to construct the monolayer that delivers the dopant, to boost the doping level in the target substrate. X-ray photoelectron spectroscopy (XPS) showed a successful grafting of the dopant adsorbate onto the SiO2 surface. The achieved doping levels after thermal annealing were similar to the doping levels acessible by MLD as demonstrated by secondary ion mass spectrometry measurements. The method shows good prospects, e.g. for use in the doping of Si nanostructures.

Highly Dispersible and Stable Anionic Boron Cluster-Graphene Oxide Nanohybrids.

An efficient process to produce boron cluster-graphene oxide nanohybrids that are highly dispersible in water and organic solvents is established for the first time. Dispersions of these nanohybrid materials in water were extraordinarily stable after one month. Characterization of hybrids after grafting of appropriate cobaltabisdicarbollide and closo-dodecaborate derivatives onto the surface of graphene oxide (GO) was done by FT-IR, XPS, and UV/Vis. Thermogravimetric analysis (TGA) clearly shows a higher thermal stability for the modified-GO nanohybrids compared to the parent GO. Of particular note, elemental mapping by energy-filtered transmission electron microscopy (EFTEM) reveals that a uniform decoration of the graphene oxide surface with the boron clusters is achieved under the reported conditions. Therefore, the resulting nanohybrid systems show exceptional physico-chemical and thermal properties, paving the way for an enhanced processability and further expanding the range of application for graphene-based materials.

Photoluminescence in Carborane-Stilbene Triads: A Structural, Spectroscopic, and Computational Study.

A set of triads in which o- and m-carborane clusters are bonded to two stilbene units through Ccluster -CH2 bonds was synthesized, and their structures were confirmed by X-ray diffraction. A study on the influence of the o- and m- isomers on the absorption and photoluminescence properties of the stilbene units in solution revealed no charge-transfer contributions in the lowest excited state, as confirmed by (TD)DFT calculations. The presence of one or two B-I groups in m-carborane derivatives does not affect the emission properties of the stilbenes in solution, probably due to the rather large distance between the iodo substituents and the fluorophore. Nevertheless, a significant redshift of the photoluminescence (PL) emission maximum in the solid state (thin films and powder samples) compared to solution was observed; this can be traced back to PL sensitization, most probably due to more densely packed stilbene moieties. Remarkably, the PL absolute quantum yields of powder samples are significantly higher than those in solution, and this was attributed to the restricted environment and the aforementioned sensitization. Thus, the bonding of the carborane clusters to two stilbene units preserves their PL behavior in solution, but produces significant changes in the solid state. Furthermore, iodinated species can be considered to be promising precursors for theranostic agents in which both imaging and therapeutic functions could possibly be combined.

Redox-Active Metallacarborane-Decorated Octasilsesquioxanes. Electrochemical and Thermal Properties.

Polyanionic and electroactive hybrids based on octasilsesquioxanes bearing metallacarborane units are developed. They show remarkable solubility in organic solvents and outstanding thermal stability. The metallacarboranes act as independent units simultaneously undergoing the reversible redox process.

Efficient Chemical Modification of Carbon Nanotubes with Metallacarboranes.

As-produced single-walled carbon nanotubes (SWCNTs) tend to aggregate in bundles due to π-π interactions. Several approaches are nowadays available to debundle, at least partially, the nanotubes through surface modification by both covalent and noncovalent approaches. Herein, we explore different strategies to afford an efficient covalent functionalization of SWCNTs with cobaltabisdicarbollide anions. Aberration-corrected HRTEM analysis reveals the presence of metallacarboranes along the walls of the SWCNTs. This new family of materials presents an outstanding water dispersibility that facilitates its processability for potential applications.

High-boron-content porphyrin-cored aryl ether dendrimers: controlled synthesis, characterization, and photophysical properties.

The synthesis and characterization of a set of poly(aryl ether) dendrimers with tetraphenylporphyrin as the core and 4, 8, 16, or 32 closo-carborane clusters are described. A regioselective hydrosilylation reaction on the allyl-terminated functions with carboranylsilanes in the presence of Karstedt's catalyst leads to different generations of boron-enriched dendrimers. This versatile approach allows the incorporation of a large number of boron atoms in the dendrimers' periphery. Translational diffusion coefficients (D) determined by DOSY NMR experiments permit estimation of the hydrodynamic radius (RH) and molecular size for each dendrimer. Furthermore, a notable correlation between D and the molecular weight (MW) is found and can be used to predict their overall size and folding properties. The UV-vis and emission behavior are not largely affected by the functionalization, therefore implying that the presence of carboranes does not alter their photoluminescence properties.

Fluorescence of new o-carborane compounds with different fluorophores: can it be tuned?

Two sets of o-carborane derivatives incorporating fluorene and anthracene fragments as fluorophore groups have been successfully synthesized and characterized, and their photophysical properties studied. The first set, comprising fluorene-containing carboranes 6-9, was prepared by catalyzed hydrosilylation reactions of ethynylfluorene with appropriate carboranylsilanes. The compound 1-[(9,9-dioctyl-fluorene-2-yl)ethynyl]carborane (11) was synthesized by the reaction of 9,9-dioctyl-2-ethynylfluorene and decaborane (B10H14). Furthermore, reactions of the lithium salt of 11 with 1 equivalent of 4-(chloromethyl)styrene or 9-(chloromethyl)anthracene yielded compounds 12 and 13. Members of the second set of derivatives, comprising anthracene-containing carboranes, were synthesized by reactions of monolithium or dilithium salts of 1-Me-1,2-C2B10H11, 1-Ph-1,2-C2B10H11, and 1,2-C2B10H12 with 1 or 2 equivalents of 9-(chloromethyl)anthracene, respectively, to produce compounds 14-16. In addition, 2 equivalents of the monolithium salts of 1-Me-1,2-C2B10H11 (Me-o-carborane) and 1-Ph-1,2-C2B10H11 (Ph-o-carborane) were reacted with 9,10-bis(chloromethyl)anthracene to produce compounds 17 and 18, respectively. Fluorene derivatives 6-9 exhibit moderate fluorescence quantum yields (32-44 %), whereas 11-13, in which the fluorophore is bonded to the Ccluster (Cc), show very low emission intensity (6 %) or complete fluorescence quenching. The anthracenyl derivatives containing the Me-o-carborane moiety exhibit notably high fluorescence emissions, with ϕF = 82 and 94 %, whereas their Ph-o-carborane analogues are not fluorescent at all. For these compounds, we have observed a correlation between the Cc-Cc bond length and the fluorescence intensity in CH2Cl2 solution, comparable to that observed for previously reported styrene-containing carboranes. Thus, our hypothesis is that for systems of this type the fluorescence may be tuned and even predicted by changing the substituent on the adjacent Cc.

Methods to produce B-C, B-P, B-N and B-S bonds in boron clusters.

Boranes, heteroboranes and metallacarboranes, all named as boron clusters, offer an alternative to typical organic molecules or organic molecular materials. Carbon and boron share the important property of self-catenation thus these elements can produce individually large and sophisticated molecules. Boron clusters and organic molecules display electronic, physical, chemical and geometrical characteristics manifestly different. These differences highlight the complementarity of organic molecules and boron clusters, and therefore the feasibility or necessity to produce hybrid molecules incorporating both types of fragments. To join these two types of fragments, or alternatively these two types of molecular compounds, tools are needed. In this review the current methods of producing boron clusters with carbon, B-C, nitrogen, B-N, phosphorus, B-P and sulphur bonds, B-S, are indicated. As there are many existing borane clusters of different sizes, heteroboranes and metallacarboranes, the revision of methods to generate the B-C, B-P, B-S, and B-N bonds has been restricted to the most widely used boron clusters; [B12H12](2-), dianionic and an example of a borane, 1,2-C2B10H12, neutral and an example of a heteroborane, and [Co(C2B9H11)2](-), monoanionic and an example of a metallacarborane.

Synthesis, characterization, and thermal behavior of carboranyl-styrene decorated octasilsesquioxanes: influence of the carborane clusters on photoluminescence.

Novel polyhedral oligomeric silsesquioxanes (POSS) or octasilsesquioxanes with carboranyl-styrene fragments attached to each corner are described. These compounds have been synthesized by olefin-metathesis reactions between octavinylsilsesquioxane and carboranyl-styrene compounds that possess different substituents (Ph, Me, or H). In all cases, these reactions, which were catalyzed by the Grubbs catalyst, are highly regioselective and yield exclusively the E isomers. The existence of the carborane cage in the POSS structure induces a remarkable thermal stability in these compounds. After combustion at 1000 °C, these carboranyl-POSS compounds exhibit a mass loss lower than 10%. The UV/Vis absorption data of these carboranyl-POSS compounds shows a slight bathochromic shift with respect to the carboranyl-styrene monomers, with an absorption maximum around 262 nm. Nevertheless, important differences in the emission spectra of the carboranyl-POSS compounds with regard to their carboranyl-styrene precursors are observed; the phenyl-o-carborane-containing POSS compound exhibits the highest fluorescence intensity (Φ(F)=44%), whereas for the POSS compound bearing the methyl substituent, and for the unsubstituted o-carborane clusters, the fluorescence intensity is much lower (Φ(F)=9 and 2%, respectively). This is precisely the reverse of what occurs with the monomers, in which the unsubstituted o-carboranyl-styrene compound exhibits the highest Φ(F), and a quenching of the fluorescence is observed in the phenyl-o-carboranyl-styrene compound. In addition, a large red shift of around 100 nm is observed for the POSS compounds with respect to their precursors. These experimental results can only be accounted for by the spatial ordering induced by the POSS core that eases interactions, which otherwise would not occur. These results have been confirmed by time-dependent density functional theory (TDDFT) calculations that exclude a photoinduced electron transfer (PET) process in the POSS compounds.

A versatile methodology for the controlled synthesis of photoluminescent high-boron-content dendrimers.

Fluorescent star-shaped molecules and dendrimers with a 1,3,5-triphenylbenzene moiety as the core and 3 or 9 carborane derivatives at the periphery, have been prepared in very good yields by following different approaches. One procedure relies on the nucleophilic substitution of Br groups in 1,3,5-tris(4-(3-bromopropoxy)phenyl)benzene with the monolithium salts of methyl and phenyl-o-carborane. The second method is the hydrosilylation reactions on the peripheral allyl ether functions of 1,3,5-tris(4-allyloxy-phenyl)benzene and 1,3,5-tris(4-(3,4,5-trisallyloxybenzyloxy)phenyl)benzene with suitable carboranyl-silanes to produce different generations of dendrimers decorated with carboranyl fragments. This approach is very versatile and allows one to introduce long spacers between the fluorescent cores and the boron clusters, as well as to obtain a high loading of boron clusters. The removal of one boron atom from each cluster leads to high-boron-content water-soluble macromolecules. Thermogravimetric analyses show a higher thermal stability for the three-functionalized compounds than for those containing 9 clusters. All compounds exhibit photoluminescent properties at room temperature under ultraviolet irradiation with high quantum yields; these depend on the nature of the cluster and the substituent on the C(cluster). Cyclic voltammetry indicates that there is no electronic communication between the core and the peripheral carboranyl fragments. Due to the high boron content of these molecules, we currently focus our research on their biocompatibility, biodistribution in cells cultures, and potential applications for boron neutron capture therapy (BNCT).

Metallacarboranes and their interactions: theoretical insights and their applicability.

This tutorial review will deal with the study of metallacarboranes and their interactions with other molecules from a theoretical point of view. This contribution is devoted to guide experimental chemists through calculations that some years ago were reserved to theoretical specialists. The widespread availability of fast computers enables nowadays studies of complex compounds (e.g. metallacarboranes) from different perspectives including simulation of NMR, infrared or Raman spectra and calculation of other properties such as atomic charges or inter-/intramolecular interactions. The insights gained on the basis of theoretical calculations are crucial for either finding novel or improving existing applications of metallacarboranes. For example, in the case of enzyme inhibitors, the interactions of the metallacarboranes with the surrounding protein and how the interaction affects the efficiency are difficult problems to study experimentally. The use of theoretical tools can provide a detailed understanding of the physico-chemical basis of the interactions and thus offers a chance to control the overall process.

Influential role of ethereal solvent on organolithium compounds: the case of carboranyllithium.

The influence of ethereal solvents (diethyl ether (Et(2)O), tetrahydrofuran (THF) or dimethoxyethane (DME)) on the formation of organolithiated compounds has been studied on the 1,2-C(2)B(10)H(12) platform. This platform is very attractive because it contains two C(c)-H adjacent units ready to be lithiated. On would expect that the closeness of both C(c)-H units would induce a higher resistance of the second C(c)-H unit being lithiated following the first lithiation. However, this is not the case, which makes 1,2-C(2)B(10)H(12) attractive to get a better understanding of the ethereal solvent influence on the lithiation process. The formation of carboranyl disubstituted species has been attributed to the existence of an equilibrium in which the carboranyl monolithiated species disproportionates into dilithium carborane and pristine carborane. The way Li(+) binds to C(c) in the carboranyl fragment and how the solvent stabilizes such a binding is paramount to drive the reaction to the generation of mono- and disubstituted carboranes. In fact, the proportion of mono- and disubstituted species is a consequence of the formation of contact ion pairs and, to a lesser extent, of separated ion pairs in ethereal solvents. All ethereal solvents generate contact ion pairs in which a large degree of covalent C(c)-Li(solvent) bonding can be assumed, according to experimental and theoretical data. Furthermore, Et(2)O tends to produce carboranyllitium ion pairs with a higher degree of contact ion pairs than THF or DME. It has been determined that for a high-yield preparation of monosubstituted 1-R-1,2-C(2)B(10)H(11), in C(c)-R (R=C, S or P) coupling reactions, the reagent type defines which is the most appropriate ethereal solvent. In reactions in which a halide is generated, as with ClPPh(2) or BrCH(2) CH=CH(2), Et(2)O appears to produce the highest degree of monosubstitution. In other situations, such as with S(8), or when no halide is generated, THF or DME facilitate the largest degree of monosubstitution. It has been shown that upon the self reaction of Li[1,2-C(2)B(10)H(11)] to produce [LiC(4)B(20)H(22)](-) the nucleophilicity of the carboranyllithium can even be further enhanced, beyond the ethereal solvent, by synergism with halide salts. The mediation of Li(+) in producing isomerizations on allyl substituents has also been demonstrated, as Et(2)O does not tend to induce isomerization, whereas THF or DME produces the propenyl isomer. The results presented here most probably can be extended to other molecular types to interpret the Li(+) mediation in C-C or other C-X coupling reactions.