Design and Synthesis of New Sulfonic Acid Functionalized Ionic Liquids as Catalysts for Esterification of Fatty Acids with Bioethanol.

In this study, three types of sulfonic acid group functionalized ionic liquids (SAILs) with a different number of catalytic groups and lipophilicity were synthesized and characterized by FT-IR, NMR, and MS analyses. Their catalytic activities were studied in a model esterification of oleic acid with ethanol; heating in a microwave reactor was also used. The experimental results indicated that SAIL, with the lipophilic alkyl chain, performed the best due to its increased solubility in the reaction mixture. Microwave heating was found to be more effective than conventional heating. Recycling experiments show that these novel SAILs can be reused without significant loss of the catalytic activity.

Cobalt Bis-Dicarbollide Enhances Antibiotics Action towards Staphylococcus epidermidis Planktonic Growth Due to Cell Envelopes Disruption.

The emergence of antibiotic resistance in opportunistic pathogens represents a huge problem, the solution for which may be a treatment with a combination of multiple antimicrobial agents. Sodium salt of cobalt bis-dicarbollide (COSAN.Na) is one of the very stable, low-toxic, amphiphilic boron-rich sandwich complex heteroboranes. This compound has a wide range of potential applications in the biological sciences due to its antitumor, anti-HIV-1, antimicrobial and antibiofilm activity. Our study confirmed the ability of COSAN.Na (in the concentration range 0.2-2.48 µg/mL) to enhance tetracycline, erythromycin, and vancomycin action towards Staphylococcus epidermidis planktonic growth with an additive or synergistic effect (e.g., the combination of 1.24 µg/mL COSAN.Na and 6.5 µg/mL TET). The effective inhibitory concentration of antibiotics was reduced up to tenfold most efficiently in the case of tetracycline (from 65 to 6.5 µg/mL). In addition, strong effect of COSAN.Na on disruption of the cell envelopes was determined using propidium iodide uptake measurement and further confirmed by transmission electron microscopy. The combination of amphiphilic COSAN.Na with antibiotics can therefore be considered a promising way to overcome antibiotic resistance in Gram-positive cocci.

Inhibitors of CA IX Enzyme Based on Polyhedral Boron Compounds.

This review describes recent progress in the design and development of inhibitors of human carbonic anhydrase IX (CA IX) based on space-filling carborane and cobalt bis(dicarbollide) clusters. CA IX enzyme is known to play a crucial role in cancer cell proliferation and metastases. The new class of potent and selective CA IX inhibitors combines the structural motif of a bulky inorganic cluster with an alkylsulfamido or alkylsulfonamido anchor group for Zn2+ ion in the enzyme active site. Detailed structure-activity relationship (SAR) studies of a large series containing 50 compounds uncovered structural features of the cluster-containing inhibitors that are important for efficient and selective inhibition of CA IX activity. Preclinical evaluation of selected compounds revealed low toxicity, favorable pharmacokinetics and ability to reduce tumor growth. Cluster-containing inhibitors of CA IX can thus be considered as promising candidates for drug development and/or for combination therapy in boron neutron capture therapy (BNCT).

Determination of acidity constants, ionic mobilities, and hydrodynamic radii of carborane-based inhibitors of carbonic anhydrases by capillary electrophoresis.

Capillary electrophoresis (CE) has been applied for determination of the thermodynamic acidity constants (pKa ) of the sulfamidoalkyl and sulfonamidoalkyl groups, the actual and limiting ionic mobilities and hydrodynamic radii of important compounds, eight carborane-based inhibitors of carbonic anhydrases, which are potential new anticancer drugs. Two types of carboranes were investigated, (i) icosahedral cobalt bis(dicarbollide)(1-) ion with sulfamidoalkyl moieties, and (ii) 7,8-nido-dicarbaundecaborate with sulfonamidoalkyl side chains. First, the mixed acidity constants, pKamix , of the sulfamidoalkyl and sulfonamidoalkyl groups of the above carboranes and their actual ionic mobilities were determined by nonlinear regression analysis of the pH dependences of their effective electrophoretic mobility measured by capillary electrophoresis in the pH range 8.00-12.25, at constant ionic strength (25 mM), and constant temperature (25°C). Second, the pKamix were recalculated to the thermodynamic pKa s using the Debye-Hückel theory. The sulfamidoalkyl and sulfonamidoalkyl groups were found to be very weakly acidic with the pKa s in the range 10.78-11.45 depending on the type of carborane cluster and on the position and length of the alkyl chain on the carborane scaffold. These pKa s were in a good agreement with the pKa s (10.67-11.27) obtained by new program AnglerFish (freeware at https://echmet.natur.cuni.cz), which provides thermodynamic pKa s and limiting ionic mobilities directly from the raw CE data. The absolute values of the limiting ionic mobilities of univalent and divalent carborane anions were in the range 18.3-27.8 TU (Tiselius unit, 1 × 10-9 m2 /Vs), and 36.4-45.9 TU, respectively. The Stokes hydrodynamic radii of univalent and divalent carborane anions varied in the range 0.34-0.52 and 0.42-0.52 nm, respectively.

Class II biocompatible E-Shell 300 3D printing material causes severe developmental toxicity in Danio rerio embryos and reduced cell proliferation in vitro - implications for 3D printed microfluidics.

Additive manufacturing is a new technology that represents a highly promising, cheap, and efficient solution for the production of various tools in the biomedicine field. In our study, the toxicity of the commercially available E-Shell 300 series photopolymer, which is used in the manufacture of hearing aids and other implants and which could be potentially exploited in microfluidic device fabrication, was tested using in vivo and in vitro biological models. We examined B14 cell proliferation in direct contact with the three-dimensional (3D)-printed material as well as in water extracts to evaluate in vitro cytotoxicity. Similarly, in vivo tests were performed using an OECD-standardized fish embryo acute toxicity (FET) test on Danio rerio embryos in direct contact with the material and in extracts as well. Despite E-Shell 300 3D-printed material being declared as class-IIa biocompatible, in the case of direct contact with both biological models, the results demonstrated a considerable negative impact on cell proliferation and severe developmental toxicity. In this study, up to 84% reduced cell proliferation in vitro and 79% mortality of in vivo models were observed. In contrast, a negligible toxic influence of E-Shell 300 water extracts was present. Four different post-processing treatments to reduce the toxicity were also tested. We observed that post-printing treatment of 3D-printed material in 96% ethanol can reduce embryonic mortality in the FET test by 71% and also completely eliminate negative effects on cell proliferation. We analyzed leachates from the polymeric structures by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, and we discovered the presence of surfactant residues. In summary, our results indicate the importance of biocompatibility testing of the 3D printing photopolymer material in direct contact with the given biological model. On the other hand, the possibility of eliminating toxic effects by an appropriate post-processing strategy opens the door for broader applications of E-Shell 300 photopolymers in the development of complex microfluidic devices for various biological applications.

Sulfonamido carboranes as highly selective inhibitors of cancer-specific carbonic anhydrase IX.

Carbonic anhydrase IX (CA IX) is a transmembrane enzyme overexpressed in hypoxic tumors, where it plays an important role in tumor progression. Specific CA IX inhibitors potentially could serve as anti-cancer drugs. We designed a series of sulfonamide inhibitors containing carborane clusters based on prior structural knowledge of carborane binding into the enzyme active site. Two types of carborane clusters, 12-vertex dicarba-closo-dodecaborane and 11-vertex 7,8-dicarba-nido-undecaborate (dicarbollide), were connected to a sulfonamide moiety via aliphatic linkers of varying lengths (1-4 carbon atoms; n = 1-4). In vitro testing of CA inhibitory potencies revealed that the optimal linker length for selective inhibition of CA IX was n = 3. A 1-sulfamidopropyl-1,2-dicarba-closo-dodecaborane (3) emerged as the strongest CA IX inhibitor from this series, with a Ki value of 0.5 nM and roughly 1230-fold selectivity towards CA IX over CA II. X-ray studies of 3 yielded structural insights into their binding modes within the CA IX active site. Compound 3 exhibited moderate cytotoxicity against cancer cell lines and primary cell lines in 2D cultures. Cytotoxicity towards multicellular spheroids was also observed. Moreover, 3 significantly lowered the amount of CA IX on the cell surface both in 2D cultures and spheroids and facilitated penetration of doxorubicin. Although 3 had only a moderate effect on tumor size in mice, we observed favorable ADME properties and pharmacokinetics in mice, and preferential presence in brain over serum.

Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX.

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis(dicarbollide)(1-) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives display subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids, and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.

Capturing a dynamically interacting inhibitor by paramagnetic NMR spectroscopy.

Transient and fuzzy intermolecular interactions are fundamental to many biological processes. Despite their importance, they are notoriously challenging to characterize. Effects induced by paramagnetic ligands in the NMR spectra of interacting biomolecules provide an opportunity to amplify subtle manifestations of weak intermolecular interactions observed for diamagnetic ligands. Here, we present an approach to characterizing dynamic interactions between a partially flexible dimeric protein, HIV-1 protease, and a metallacarborane-based ligand, a system for which data obtained by standard NMR approaches do not enable detailed structural interpretation. We show that for the case where the experimental data are significantly averaged to values close to zero the standard fitting of pseudocontact shifts cannot provide reliable structural information. We based our approach on generating a large ensemble of full atomic models, for which the experimental data can be predicted, ensemble averaged and finally compared to the experiment. We demonstrate that a combination of paramagnetic NMR experiments, quantum chemical calculations, and molecular dynamics simulations offers a route towards structural characterization of dynamic protein-ligand complexes.

The synthesis and structural characterization of polycyclic derivatives of cobalt bis(dicarbollide)(1(-)).

The cobalt bis(dicarbollide) anion [(1,2-C2B9H11)2-3,3'-Co](-) (1(-)) is an increasingly important building block for the design of new biologically active compounds. Here we report the reactions of lithiated 1(-) with N-(ω-bromoalkyl)phthalimides Br-(CH2)n-N(CO)2NC6H4 (where n = 1 to 3) that give a number of new compounds substituted at dicarbollide carbon atom positions. For n = 2 and 3, substitution of the cobalt bis(dicarbollide) anion is accompanied by cyclocondensation of the organic moieties to give polycyclic ring structures attached to the cage. Predominant products correspond to oxazolo[2,3-a]isoindol-5(9bH)-1,2,3-dihydro-9b-yl)-(1-cobalt(III) bis(1,2-dicarbollide)(1(-)) (2(-)) and 1-(2H-[1,3]-oxazino[2,3-a]isoindol-6(10bH)-1,3,4-dihydro-10b-yl)-(1-cobalt(III) bis(1,2-dicarbollide)(1(-)) (4(-)) ions with isoindolone functions containing either five- or six-membered lateral oxazine rings. Additionally, products (tetrahydro-2-benzo[4,5]furan-1(3H)-1-[3,3]-yl-)-1,1'-µ-cobalt(III) bis(1,2-dicarbollide)(1(-)) (3(-)) and (2-(azetidin-yl-carbonyl)benzoyl-)-1-cobalt(III) bis(1,2-dicarbollide)(1(-)) (5(-)) were isolated, which display unusual cyclic structures featuring a bicyclic benzofuranone ring attached in a bridging manner by a quarternary carbon to two skeletal carbon atoms and a ketobenzoic acid amide substituent with a side azetidine ring. However, in the case of n = 1, only the anticipated methylene amine derivative [(1-NH2CH2-1,2-C2B9H11)(1',2'-C2B9H11)2-3,3'-Co](-) (6(-)) was isolated in low yield after cleavage of the phthalimide intermediate species. The molecular structures of all isolated cyclic products 2(-) to 5(-) were confirmed by single-crystal X-ray diffraction studies, and the structure of cobalt bis(dicarbollide)-1-CH2NH2 6(-) was delineated using density functional theory applied at BP86/AE1 level in combination with NMR spectroscopy. Thus, the synthetic method described herein presents a facile route to new cobalt bis(dicarbollide) derivatives substituted by polycyclic structural motifs with potential biological activity.

Luminescent hydrogel particles prepared by self-assembly of ß-cyclodextrin polymer and octahedral molybdenum cluster complexes.

A series of luminescent octahedral molybdenum cluster complexes were obtained by treating Na2[Mo6I8(OMe)6] with icosahedral closo-dicarbaborane C-carboxylic acids in refluxing tetrahydrofuran. The study of the photophysical properties of Na2[Mo6I8(1-OOC-1,2-closo-C2B10H11)6] (1), Na2[Mo6I8(1-OOC-1,7-closo-C2B10H11)6] (2), and Na2[Mo6I8(1-OOC-1,12-closo-C2B10H11)6] (3) in acetonitrile revealed a red luminescence with high quantum yields up to 0.93 for 2, an efficient quenching of the luminescence by oxygen, and high quantum yields of singlet oxygen formation of approximately 0.7. Self-assembly between compound 2 and ß-cyclodextrin polymer led to monodisperse hydrogel particles with a diameter of approximately 200 nm and unchanged luminescence spectra and kinetics features over 14 days. In contrast, bare cluster complex 2 in water formed aggregates and hydrolyzed over the time as indicated by a progressive red shift of the luminescence maxima. The invariance of key photophysical parameters of the hydrogel particles coupled with a high oxygen sensitivity of the luminescence are attractive features for long-term biological experiments involving optical oxygen probing. In addition, this hydrogel is a singlet oxygen sensitizer in water with promising properties for photodynamic therapy.

Carborane-based carbonic anhydrase inhibitors: insight into CAII/CAIX specificity from a high-resolution crystal structure, modeling, and quantum chemical calculations.

Carborane-based compounds are promising lead structures for development of inhibitors of carbonic anhydrases (CAs). Here, we report structural and computational analysis applicable to structure-based design of carborane compounds with selectivity toward the cancer-specific CAIX isoenzyme. We determined the crystal structure of CAII in complex with 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane at 1.0 Å resolution and used this structure to model the 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane interactions with CAIX. A virtual glycine scan revealed the contributions of individual residues to the energy of binding of 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane to CAII and CAIX, respectively.

Synthesis, characterisation and some chemistry of C- and B-substituted carboxylic acids of cobalt bis(dicarbollide).

Low temperature reactions of lithiated cobalt bis(1,2-dicarbollide)(1-) (1⁻) in DME with carbon dioxide leads to the substitution of 1⁻ at the C-atoms by carboxy function(s). This results in a good yield formation of monosubstituted and disubstituted products of formulations [(1-HOOC-1,2-C2B9H10)(1',2'-C2B9H11)-3,3'-Co)](-) (2⁻) and [(HOOC)2-(1,2-C2B9H10)2-3,3'-Co](-) (3a,b⁻), respectively. Indeed, the latter compound is in fact a mixture of two diastereoisomers, denoted here as 1,1'-anti (3a⁻) and 1,2'-syn-isomer (3b⁻), from which only the former major species (3a⁻) could be isolated in pure form. Considerations about stereochemistry of these species are supported by geometry optimizations and calculations of (11)B NMR shifts at the GIAO-DFT level. In addition, three monocarboxylic acids with three different linear spacers between the carboxy groups and the cage are reported. The first one of the formula [(1-HOOC-CH2-1,2-C2B9H10)(1',2'-C2B9H11)-3,3'-Co](-) (5⁻) results in a lithiation followed by reaction with BrCH2COOEt and hydrolysis of the respective ethyl ester (4⁻). Another one with ethylene chain [(1-HOOC-(CH2)2-1,2-C2B9H10)(1',2'-C2B9H11)-3,3'-Co](-) (6⁻) was prepared by the oxidation of a hydroxypropyl derivative of the ion 1⁻. The sole representative of B-substituted species of the formulation [8-(HOOC-CH2-O-1,2-C2B9H10)(1',2'-C2B9H11)-3,3'-Co](-) (7⁻) is prepared by alkylation of the known 8-hydroxy derivatives of the ion 1⁻ by BrCH2COOEt and alkaline hydrolysis. A synthetic route to active nitrofenyl esters (8⁻, 9⁻ and 10⁻) is described here based on the respective acids 5⁻ to 7⁻. As verified, the nitrophenyl esters provide easy access to the formation of amidic bonds between the boron cage and organic primary amino functions. Examples of compounds containing butylamide or benzylamide [(1-RNHOC-(CH2)n-1,2-C2B9H10)(1',2'-C2B9H11)-3,3'-Co](-) (n = 1,2; R = Bu 11a,b⁻, R = Bn: 12a,b⁻) end group are described. Also the possibility of inter-connecting two clusters of the anion 1⁻ via the amidic bond is shown in derivative (13⁻). These methods are applicable in the synthesis of a variety of functional molecules, particularly those applicable in drug design, surface modifications, and material science.

Carborane-based carbonic anhydrase inhibitors.

CA inhibitors: Human carbonic anhydrases (CAs) are diagnostic and therapeutic targets. Various carborane cages are shown to act as active-site-directed inhibitors, and substitution with a sulfamide group and other substituents leads to compounds with high selectivity towards the cancer-specific isozyme IX. Crystal structures of the carboranes in the active site provide information that can be applied to the structure-based design of specific inhibitors.

Direct and facile synthesis of carbon substituted alkylhydroxy derivatives of cobalt bis(1,2-dicarbollide), versatile building blocks for synthetic purposes.

Reactions of lithiated cobalt bis(1,2-dicarbollide)(1(-)) anion (1(-)) in presence of paraformaldehyde, ethylene oxide or trimethylene oxide led to the substitution of 1(-) at the C-atoms resulting in the high yield formation of monosubstituted alkylhydroxy derivatives [(1-HO(CH(2))(n)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(III)](-) (n = 1-3) isolated as caesium salts (Cs2, Cs3, Cs4) along with disubstituted products of general formulation [(HO(CH(2))(n)-1,2-C(2)B(9)H(10))(2)-3,3'-Co(III)](-) (n = 1-3) (Cs5, Cs6 and Cs7). Disubstituted compounds are in fact a mixture of diastereoisomers denoted as 1,1'-anti(rac-), 1,2'-syn- and in case of Cs6 and Cs7 also 1,2-vicinal-isomer, from which only the anti-isomer could be isolated in pure form in case of shorter chain compounds Cs5 and Cs6. All these alkylhydroxy derivatives can serve as versatile precursors for the generation of a variety of functional molecules. Thus, reaction of Me(3)NH4 with NaH and one equivalent of POCl(3) provided after hydrolysis the phosphorylated [(1-(HO)(2)P(O)OC(3)H(6)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(III)](-) derivative, isolated in the form of trimethylammonium salt, Me(3)NH8 as the main product whereas reaction with half of the equivalent produces a high yield of phosphoric acid diester (Me(3)NH)(2)9 comprising in its structure two cages connected via propyl spacers to the central part. The calcium salt Ca(10)(2) of bridged ion [µ-(HOP(O)(OC(3)H(6))(2))-(1,2-C(2)B(9)H(10))(2)-3,3'-Co(III)](-) resulted from reaction of Me(3)NH7 with NaH and one equivalent of POCl(3) followed by hydrolysis and addition of CaCl(2). All new compounds were characterized by multinuclear NMR spectroscopy and mass spectrometry and the structure of Me(3)NH3 and that of the respective salts of the pure anti-stereoisomer of dialkylhydroxy derivatives Cs5 and Me(3)NH6 were established by X-ray crystallography.

Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes.

HIV protease (HIV PR) is a primary target for anti-HIV drug design. We have previously identified and characterized substituted metallacarboranes as a new class of HIV protease inhibitors. In a structure-guided drug design effort, we connected the two cobalt bis(dicarbollide) clusters with a linker to substituted ammonium group and obtained a set of compounds based on a lead formula [H(2)N-(8-(C(2)H(4)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co)(2)]Na. We explored inhibition properties of these compounds with various substitutions, determined the HIV PR:inhibitor crystal structure, and computationally explored the conformational space of the linker. Our results prove the capacity of linker-substituted dual-cage cobalt bis(dicarbollides) as lead compounds for design of more potent inhibitors of HIV PR.

Toward the synthesis of high boron content polyanionic multicluster macromolecules.

Reported are further consequences of the dioxane ring opening in [3,3'-Co(8-(CH(2)CH(2)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))], [1], with 12-vertex carborane mono- and dianions. The removal of one BH vertex from the 1,2-closo-C(2)B(9)H(12) part of the double-cluster monoanions of type [1''-X-2''-R-closo-1'',2''-C(2)B(10)H(11)](-), [2](-) (where X = [3,3'-Co(8-(CH(2)CH(2)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))](-) and R = H, [2](-); CH(3), [8](-) and C(6)H(5), [9](-)), via heating with ethanolic KOH or CsF led to the isolation of a series of orange dianions having the general formula [7''-X-8''-R-7'',8''-nido -C(2)B(9)H(11)](2-) (R = H, [11](2-); CH(3), [12](2-); and C(6)H(5), [13](2-)). The same procedure applied to the dianionic triple-cluster compound [1'',2''-X(2)-1'',2''-closo-C(2)B(10)H(10)](2-), [5](2-), yielded the trianionic species [7'',8''-X(2)-7'',8''-nido -C(2)B(9)H(10)](3-), [14](3-). Boron degradation of the related 1,7-carborane anion [1''-X-1'',7''-closo-C(2)B(10)H(11)](-), [3](-), was achieved upon heating with CsF in ethylene glycol to generate the [7''-X-7'',9''-nido-C(2)B(9)H(11)](2-), [15](2-), dianion. However, the degradation of the corresponding [1'',7''-X(2)-1'',7''-closo-C(2)B(10)H(10)](2-), [6](2-), dianion under the same conditions led only to the cleavage of the ether chain with no possible isolation of the expected [7'',9''-X(2)-7'',9''-nido-C(2)B(9)H(10)](3-) trianion. The study has been complemented by experimental procedures leading to the still not fully reported starting monoanionic compounds [2](-), [3](-), [8](-) and [9](-) and to the starting dianions [5](2-) and [6](2-). The anions containing the eleven-vertex moiety can be isolated as either Cs(+) or [N(CH(3))(4)](+) salts and can be converted into other salts via metathesis with suitable countercations. The structures of all compounds isolated in this study have been suggested on the basis of NMR and mass spectrometry methods. The disarticulation of complex (11)B NMR spectra has been successfully achieved in this work and has been proven to be a powerful tool for the characterization of multicluster boron-containing molecules.

Boron(8) substituted nitrilium and ammonium derivatives, versatile cobalt bis(1,2-dicarbollide) building blocks for synthetic purposes.

The reaction of the cobalt bis(dicarbollide)(1-)() ion in the presence of t-butylbromide, acting as a potent Lewis acid activator, leads to the clean substitution of by the N-atom of acetonitrile (or benzonitrile), thus resulting in the smooth formation of [(8-RCN)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](0) (R = CH(3) or C(6)H(5)) ( and ). These compounds can serve as versatile precursors for the generation of a variety of other synthetically useful functional groups. The nitrogen atom of the nitrile C[triple bond, length as m-dash]N- bond in and is prone to the facile addition of nucleophiles. Thus, alkaline hydrolysis of and in aqueous alcohols furnishes high yields of the corresponding B(8)-N-alkylamides [(8-RC(O)=NH)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](-), where R = CH(3) or C(6)H(5) ( and ). The reactions with butyl and diethyl amine result in the high-yield formation of 8-alkylamidine derivatives [(8-(3)R(2)RNH-(1)RC[double bond, length as m-dash]N)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](0), where (1)R = CH(3), (2)R = H, (3)R = C(4)H(9), (), (1)R = C(6)H(5), (2)R = (3)R = C(2)H(5) () or (1)R = C(6)H(5), (2)R = (3)R = C(2)H(5) (). Hydrazinolysis of provides a high yield of the zwitterionic [(8-H(3)N)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](0) (), whereas reduction of the nitrile group in and using BH(3).SMe(2) affords the respective alkylammonium derivatives [(8-RH(2)N)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](0), where R = -C(2)H(5) () or -CH(2)C(6)H(5) () in moderate yields. Compound can also be prepared by alkylation of along with dibenzylderivative (). A further example of alkylation is the ring cleavage of the 3-hydroxypropanesulfonic acid gamma-sultone producing a compound with alkyl ammonium sulfonic acid substitution [(8-O(3)SC(3)H(6)NH(2))-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](-) () All new compounds were characterized by multinuclear NMR spectroscopy and mass spectrometry and the structures of compounds , , and were established by X-ray crystallography.