The Zwitterion [8,8′-μ-CH₂O(CH₃)-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁰ as a Versatile Building Block To Introduce Cobalt Bis(Dicarbollide) Ion into Organic Molecules

The synthesis of a new bridged [8,8′-μ-CH₂O­(CH₃)-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁰ derivative (<b>2</b>), arising from the acid-catalyzed reaction of cobalt bis­(1,2-dicarbollide)(1−) ion with formaldehyde, is reported. The proposed reaction path is supported by the isolation of side products including two zwitterionic compounds, the known bridged [8,8′-μ-(CH₃O)-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁰ derivative (<b>3</b>), the new zwitterion [(8-(CH₃)₂O-1,2-C₂B₉H₁₀)-(1′,2′-C₂B₉H₁₁)-3,3′-Co]⁰ (<b>4</b>), and two anionic compoundsthe known [(8,8′-Cl₂-1,2-C₂B₉H₁₀)₂-3,3′-Co]⁻ and the newly characterized dimethoxy derivative [(8,8′-(CH₃O)₂-1,2-C₂B₉H₁₀)₂-3,3′-Co]⁻ of the cobalt bis­(dicarbollide) ion. Compound <b>2</b> serves as a versatile building block for the construction of zwitterionic derivatives, as exemplified by the synthesis of a series of compounds of general formulation [(8-X-CH₂-1,2-C₂B₉H₁₀)­(8′-CH₃O-1′,2′-C₂B₉H₁₀)-3,3′-Co]⁰ (<b>6</b>). Compounds of type <b>6</b> bear organic end groups (X = NC₅H₅ (<b>6a</b>), C₆H₁₃NH₂ (<b>6b</b>), 2-HOC₂H₄NH₂ (<b>6c</b>), (C₆H₅)₃P (<b>6d</b>)) adjacent to the cluster via a methylene spacer. The reactions with alcoholates or phenolates, demonstrated by the isolation of a derivative with X = 1-O­(4-<i>t</i>-Bu-C₆H₄) (<b>7</b>^–<b></b>) in low yield, seem less advantageous due to the competing demethylation of the oxonium bridge in <b>2</b>, which results in the preferential formation of the anion [8,8′-μ-CH₃O-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁻ (<b>8</b>^<b>–</b>). A similar side reaction was found to occur in the synthesis of a tetrasubstituted <i>tert</i>-butyl-calix­[4]­arene (<b>9</b>^<b>–</b>), where one calixarene OH site was methylated producing the metallacarborane ion <b>8</b>^<b>–</b> instead of the bridge opening. The molecular structures of <b>6a</b>,<b>c</b>–<b>e, 8</b>^<b>–</b>, and <b>9</b>^<b>–</b> were determined by single-crystal X-ray diffraction analyses, and all compounds were characterized by high-resolution NMR (¹H, ¹³C, and ¹¹B) and mass spectrometry

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]⁻ (<b>1</b>^<b>–</b>) is an increasingly important building block for the design of new biologically active compounds. Here we report the reactions of lithiated <b>1</b>^<b>–</b> with <i>N</i>-(ω-bromoalkyl)­phthalimides Br-(CH₂)_<i>n</i>-N­(CO)₂NC₆H₄ (where <i>n</i> = 1 to 3) that give a number of new compounds substituted at dicarbollide carbon atom positions. For <i>n</i> = 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-<i>a</i>]­isoindol-5­(9b<i>H</i>)-1,2,3-dihydro-9<i>b-</i>yl)-(1-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>2</b>^<b>–</b>) and 1-(2<i>H</i>-[1,3]-oxazino­[2,3-<i>a</i>]­isoindol-6­(10b<i>H</i>)-1,3,4-dihydro-10<i>b</i>-yl)-(1-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>4</b>^<b>–</b>) ions with isoindolone functions containing either five- or six-membered lateral oxazine rings. Additionally, products (tetrahydro-2-benzo­[4,5]­furan-1­(3<i>H</i>)-1-[3,3]-yl-)-1,1′-μ-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>3</b>^<b>–</b>) and (2-(azetidin-yl-carbonyl)­benzoyl-)-1-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>5</b>^<b>–</b>) 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 <i>n</i> = 1, only the anticipated methylene amine derivative [(1-NH₂CH₂-1,2-C₂B₉H₁₁)­(1′,2′-C₂B₉H₁₁)₂-3,3′-Co]⁻ (<b>6</b>^<b>–</b>) was isolated in low yield after cleavage of the phthalimide intermediate species. The molecular structures of all isolated cyclic products <b>2</b>^<b>–</b> to <b>5</b>^<b>–</b> were confirmed by single-crystal X-ray diffraction studies, and the structure of cobalt bis­(dicarbollide)-1-CH₂NH₂ <b>6</b>^<b>–</b> 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

The Zwitterion [8,8′-μ-CH₂O(CH₃)-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁰ as a Versatile Building Block To Introduce Cobalt Bis(Dicarbollide) Ion into Organic Molecules

The synthesis of a new bridged [8,8′-μ-CH₂O­(CH₃)-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁰ derivative (<b>2</b>), arising from the acid-catalyzed reaction of cobalt bis­(1,2-dicarbollide)(1−) ion with formaldehyde, is reported. The proposed reaction path is supported by the isolation of side products including two zwitterionic compounds, the known bridged [8,8′-μ-(CH₃O)-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁰ derivative (<b>3</b>), the new zwitterion [(8-(CH₃)₂O-1,2-C₂B₉H₁₀)-(1′,2′-C₂B₉H₁₁)-3,3′-Co]⁰ (<b>4</b>), and two anionic compoundsthe known [(8,8′-Cl₂-1,2-C₂B₉H₁₀)₂-3,3′-Co]⁻ and the newly characterized dimethoxy derivative [(8,8′-(CH₃O)₂-1,2-C₂B₉H₁₀)₂-3,3′-Co]⁻ of the cobalt bis­(dicarbollide) ion. Compound <b>2</b> serves as a versatile building block for the construction of zwitterionic derivatives, as exemplified by the synthesis of a series of compounds of general formulation [(8-X-CH₂-1,2-C₂B₉H₁₀)­(8′-CH₃O-1′,2′-C₂B₉H₁₀)-3,3′-Co]⁰ (<b>6</b>). Compounds of type <b>6</b> bear organic end groups (X = NC₅H₅ (<b>6a</b>), C₆H₁₃NH₂ (<b>6b</b>), 2-HOC₂H₄NH₂ (<b>6c</b>), (C₆H₅)₃P (<b>6d</b>)) adjacent to the cluster via a methylene spacer. The reactions with alcoholates or phenolates, demonstrated by the isolation of a derivative with X = 1-O­(4-<i>t</i>-Bu-C₆H₄) (<b>7</b>^–<b></b>) in low yield, seem less advantageous due to the competing demethylation of the oxonium bridge in <b>2</b>, which results in the preferential formation of the anion [8,8′-μ-CH₃O-(1,2-C₂B₉H₁₀)₂-3,3′-Co]⁻ (<b>8</b>^<b>–</b>). A similar side reaction was found to occur in the synthesis of a tetrasubstituted <i>tert</i>-butyl-calix­[4]­arene (<b>9</b>^<b>–</b>), where one calixarene OH site was methylated producing the metallacarborane ion <b>8</b>^<b>–</b> instead of the bridge opening. The molecular structures of <b>6a</b>,<b>c</b>–<b>e, 8</b>^<b>–</b>, and <b>9</b>^<b>–</b> were determined by single-crystal X-ray diffraction analyses, and all compounds were characterized by high-resolution NMR (¹H, ¹³C, and ¹¹B) and mass spectrometry

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]⁻ (<b>1</b>^<b>–</b>) is an increasingly important building block for the design of new biologically active compounds. Here we report the reactions of lithiated <b>1</b>^<b>–</b> with <i>N</i>-(ω-bromoalkyl)­phthalimides Br-(CH₂)_<i>n</i>-N­(CO)₂NC₆H₄ (where <i>n</i> = 1 to 3) that give a number of new compounds substituted at dicarbollide carbon atom positions. For <i>n</i> = 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-<i>a</i>]­isoindol-5­(9b<i>H</i>)-1,2,3-dihydro-9<i>b-</i>yl)-(1-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>2</b>^<b>–</b>) and 1-(2<i>H</i>-[1,3]-oxazino­[2,3-<i>a</i>]­isoindol-6­(10b<i>H</i>)-1,3,4-dihydro-10<i>b</i>-yl)-(1-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>4</b>^<b>–</b>) ions with isoindolone functions containing either five- or six-membered lateral oxazine rings. Additionally, products (tetrahydro-2-benzo­[4,5]­furan-1­(3<i>H</i>)-1-[3,3]-yl-)-1,1′-μ-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>3</b>^<b>–</b>) and (2-(azetidin-yl-carbonyl)­benzoyl-)-1-cobalt­(III) bis­(1,2-dicarbollide)­(1^–) (<b>5</b>^<b>–</b>) 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 <i>n</i> = 1, only the anticipated methylene amine derivative [(1-NH₂CH₂-1,2-C₂B₉H₁₁)­(1′,2′-C₂B₉H₁₁)₂-3,3′-Co]⁻ (<b>6</b>^<b>–</b>) was isolated in low yield after cleavage of the phthalimide intermediate species. The molecular structures of all isolated cyclic products <b>2</b>^<b>–</b> to <b>5</b>^<b>–</b> were confirmed by single-crystal X-ray diffraction studies, and the structure of cobalt bis­(dicarbollide)-1-CH₂NH₂ <b>6</b>^<b>–</b> 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

Three Isomers of Aryl-Substituted Twelve-Vertex Ferratricarbollides

A series of the first types of monoaryl-substituted 12-vertex ferratricarbollide complexes of general constitution [1-(CpFe)-<i>closo</i>-ArC₃B₈H₁₀] (where Ar = C₆H₅, 1′-C₁₀H₇, 2′-C₁₀H₇) with three different aryl substituents and arrangements of cluster carbon vertexes were isolated from high-temperature reactions between 8-Ar-<i>nido</i>-7,8,9-C₃B₈H₁₁ compounds and [CpFe­(CO)₂]₂. The Fe complexation is accompanied by extensive rearrangement of the cluster carbon atoms over the 12-vertex cage

Inorganic Polyhedral Metallacarborane Inhibitors of HIV Protease: A New Approach to Overcoming Antiviral Resistance

HIV protease (PR) is a prime target for rational anti-HIV drug design. We have previously identified icosahedral metallacarboranes as a novel class of nonpeptidic protease inhibitors. Now we show that substituted metallacarboranes are potent and specific competitive inhibitors of drug-resistant HIV PRs prepared either by site-directed mutagenesis or cloned from HIV-positive patients. Molecular modeling explains the inhibition profile of metallacarboranes by their unconventional binding mode