Synthesis and Antibacterial Activity Studies of the Conjugates of Curcumin with closo-Dodecaborate and Cobalt Bis(Dicarbollide) Boron Clusters

A series of novel conjugates of cobalt bis(dicarbollide) and closo-dodecaborate with curcumin were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition. These conjugates were tested for antibacterial activity. It was shown that all derivatives are active when exposed to Bacillus cereus ATCC 10702 and are not active against Gram-negative microorganisms and Candida albicans at the maximum studied concentration of 1000 mg/L. The conjugate of alkynyl-curcumin with azide synthesized from the tetrahydropyran derivative of cobalt bis(dicarbollide) exhibited activity against Gram-positive microorganisms: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and the clinical isolate MRSA 17, that surpassed curcumin by 2–4 times.     

Synthesis of cobalt bis(dicarbollide) conjugates with natural chlorins by the Sonogashira reaction

Novel boron-containing conjugates based on the alkynylated cobalt bis(dicarbollide) anion and chlorin e ₆ and purpurinimide p-iodophenyl derivatives were synthesized by the Sonogashira reaction. These conjugates can accumulate in the cancer cell cytoplasm and can be considered as potential candidates for using in boron neutron capture therapy of tumors.     

A novel approach to the synthesis of amino acids based on cobalt bis(dicarbollide)

A novel approach to the synthesis of boron-containing amino acids based on ring opening of cyclic oxonium derivatives of polyhedral boron hydrides under the action of the terminal functional groups of natural amino acids was proposed. This approach was successfully implemented for the synthesis of cobalt bis(dicarbollide) — tyrosine conjugate.     

New boron-containing 2′-deoxyadenosines

Conjugates of polyhedral boron hydrides with deoxyadenosine were synthesized by the opening of cyclic oxonium derivatives of closo-dodecaborate and cobalt bis(1,2-dicarbollide) with 2′-deoxyadenosine derivatives containing a nucleophilic group in the substituent at C(8). Biological studies of the derivatives obtained for cytotoxicity revealed that the derivatives based on closo-dodecaborate did not exhibit cytotoxicity. The conjugates obtained can be used in further biological trials as potential agents for boron neutron capture therapy of cancer.     

Novel types of boronated chlorin e6 conjugates via ‘click chemistry’

Conjugates of chlorin e₆ with closo‐dodecaborate and cobalt bis(dicarbollide) anions were synthesized for the first time in high yields using the advanced ‘click’ methodology. In vitro study on A549 human lung adenocarcinoma cells revealed that the synthesized boronated conjugates are able to penetrate and accumulate in cancer cells, but their intracellular concentration is not sufficient for effective photodynamic and boron neutron capture therapy of cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis and cytotoxicity of novel cholesterol–cobalt bis(dicarbollide) conjugates

The novel conjugates of cholesterol with cobalt – bis(dicarbollide) were synthesized by the ring-opening reactions of the cyclic oxonium derivatives of [3,3′-Co(C₂B₉H₁₁)₂]^– with the OH group of cholesterol 2-hydroxyethyl ether. The compounds obtained were tested for toxicity to glioblastoma U-87 MG cells and human embryo fibroblasts FECH-15 cells     

Synthesis, structures, and conductivities of salts (BEDT-TTF)[9,9′(12′)-I2-3,3′-Co(1,2-C2B9H10)2] and (TTF)[9,9′,12,12′-I4-3,3′-Co(1,2-C2B9H9)2]

The radical cation salts of tetrathiafulvalene (TTF) and bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) with iodo derivatives of cobalt bis(dicarbollide), (TTF)[9,9′,12,12′-I₄-3,3′-Co(1,2-C₂B₉H₉)₂] and (BEDT-TTF)[9,9′(12′)-I₂-3,3′-Co(1,2-C₂B₉H₁₀)₂], respectively, were synthesized and their crystal structures were determined. The introduction of iodine atoms into the lower rim of the dicarbollide ligands, unlike the substitution at the upper rim, leads to insignificant changes in the crystal structure and the conductivity of the radical cation salts compared to the analogous salts based on unsubstituted cobalt bis(dicarbollide).     

Capillary electrophoresis of boron cluster compounds in aqueous and nonaqueous solvents

The electrophoretic properties of boron cluster compounds were determined in water, methanol and ACN as solvents of the BGE and discussed based on the principles of ion migration. Two types of boron cluster compounds were investigated. One type consisted of derivatives of the nido-7,8-dicarbaundecaborate cluster, the other types are derivatized cobalt bis(dicarbollide) ions (COSANs) whose central cobalt atom is sandwiched by two 7,8-dicarbaundecaborate clusters. The BGE in all solvents was acetate/acetic acid buffer with pH 4.75 in water, 9.7 in methanol and 22.3 in ACN, respectively, at different ionic strength between 5 and 30 mM. The dependence of the mobility on ionic strength could not be explained by the theory of Debye, Hückel and Onsager, but good agreement was found upon considering an ion size parameter. Limiting mobilities were derived by curve fitting, and by the aid of the solvent viscosities the hydrodynamic radii of the analyte anions were calculated. They are between 0.25 and 0.48 nm, and were nearly independent of the solvent. Electrophoresis of the analytes in a BGE consisting of 6 mM perchloric acid in ACN allows the conclusion that the present boron cluster compounds behave as stronger acids than perchloric acid.     

Synthesis of cobalt and nickel 6,6′-diphenylbis(dicarbollides)

Russian Chemical Bulletin - 6,6′-Diphenyl derivatives of cobalt and nickel bis(dicarbollide) were synthesized starting from nido-carborane by the insertion—deboronation—insertion...     

Bis(dicarbollide) Complexes of Transition Metals as a Platform for Molecular Switches. Study of Complexation of 8,8′-Bis(methylsulfanyl) Derivatives of Cobalt and Iron Bis(dicarbollides)

Complexation of the 8,8′-bis(methylsulfanyl) derivatives of cobalt and iron bis(dicarbollides) [8,8′-(MeS)₂-3,3′-M(1,2-C₂B₉H₁₀)₂]⁻ (M = Co, Fe) with copper, silver, palladium and rhodium leads to the formation of the corresponding chelate complexes, which is accompanied by a transition from the transoid to the cisoid conformation of the bis(dicarbollide) complex. This transition is reversible and can be used in design of coordination-driven molecular switches based on transition metal bis(dicarbollide) complexes. The solid-state structures of {(Ph₃P)ClPd[8,8′- (MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂-κ²-S,S′]} and {(COD)Rh[8,8′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂-κ²-S,S′]} were determined by single crystal X-ray diffraction.     

Electrochemistry of Cobalta Bis(dicarbollide) Ions Substituted at Carbon Atoms with Hydrophilic Alkylhydroxy and Carboxy Groups

In this study we explore the effect on the electrochemical signals in aqueous buffers of the presence of hydrophilic alkylhydroxy and carboxy groups on the carbon atoms of cobalta bis(dicarbollide) ions. The oxygen-containing exo-skeletal substituents of cobalta bis(dicarbollide) ions belong to the perspective building blocks that are considered for bioconjugation. Carbon substitution provides wider versatility and applicability in terms of the flexibility of possible chemical pathways. However, until recently, the electrochemistry of compounds substituted only on boron atoms could be studied, due to the unavailability of carbon-substituted congeners. In the present study, electrochemistry in aqueous phosphate buffers is considered along with the dependence of electrochemical response on pH and concentration. The compounds used show electrochemical signals around −1.3 and +1.1 V of similar or slightly higher intensities than in the parent cobalta bis(dicarbollide) ion. The signals at positive electrochemical potential correspond to irreversible oxidation of the boron cage (the C2B9 building block) and at negative potential correspond to the reversible redox process of (CoIII/CoII) at the central atom. Although the first signal is typically sharp and its potential can be altered by a number of substituents, the second signal is complex and is composed of three overlapping peaks. This signal shows sigmoidal character at higher concentrations and may be used as a diagnostic tool for aggregation in solution. Surprisingly enough, the observed effects of the site of substitution (boron or carbon) and between individual groups on the electrochemical response were insignificant. Therefore, the substitutions would preserve promising properties of the parent cage for redox labelling, but would not allow for the further tuning of signal position in the electrochemical window.     

Synthesis,cytotoxicity and antiviral activity studies of the conjugates of cobalt bis(1,2-dicarbollide)(-I) with 5-ethynyl-2′-deoxyuridine and its cyclic derivatives

A series of novel conjugates of cobalt bis(1,2-dicarbollide)(-I) with 5-ethynyl-2′-deoxyuridine and its cyclic derivatives were synthesized. Conjugates with 5-ethynyl-2-deoxyuridine were prepared by the direct Sonogashira coupling of a series of cobalt bis(1,2-dicarbollide)(-I) terminal alkynes and 5-iodo-2′-deoxyuridine. Their furo[2,3-d]pyrimidin-2(3H)-one isomers were obtained either by intermolecular cyclization of the above conjugates or by Sonogashira coupling using Pd/C as a catalyst. Action of ammonia on these furo[2,3-d]pyrimidin-2(3H)-one conjugates resulted in pyrrolo[2,3-d]pyrimidin-2(3H)-one conjugates. Most of the designed compounds have shown low cytotoxicity in several cell lines. Some 5-ethynyl-2-deoxyuridine and furo[2,3-d]pyrimidin-2(3H)-one conjugates have also presented antiviral activity.     

Unfairly forgotten member of the iodocarborane family: synthesis and structural characterization of 8-iodo-1,2-dicarba-closo-dodecaborane, its precursors, and derivatives

8-Iodo-1,2-dicarba-closo-dodecaborane (7) was prepared in three steps starting from decaborane-14 with 20% overall yield. In the presence of nucleophiles, compound 7 undergoes selective removal of the boron vertex in the position para to the iodine substituent to form the anionic nido-carborane 1-iodo-7,8-dicarba-nido-undecaborate. Capping of the corresponding dicarbollide dianion with BI(3) led to formation of the new carborane, 3,10-diiodo-1,2-dicarba-closo-dodecaborane (15). The same dicarbollide dianion reacts with cobalt and nickel acetylacetonates in anhydrous tetrahydrofuran to form the corresponding bis(dicarbollide) complexes with excellent yields. All compounds were characterized by multinuclear NMR and high-resolution mass spectroscopy. Structures of 2-iododecaborane (2), 8-iodo-1,2-dicarba-closo-dodecaborane (7), 1-ethoxycarbonyl-8-iodo-1,2-dicarba-closo-dodecaborane (10), cesium 1-iodo-7,8-dicarba-nido-undecaborate (13), 3,10-diiodo-1,2-dicarba-closo-dodecaborane (15), and cesium 3,3'-commo-(10-iodo-1,2-dicarba-3-cobalta-closo-dodecaborane)-(10'-iodo-1',2'-dicarba-3'-cobalta-closo-dodecaborane) (16) were established by X-ray analysis of single crystals.     

Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides

A series of boron-containing lipids were prepared by reactions of cyclic oxonium derivatives of polyhedron boranes and metallacarboranes (closo-dodecaborate anion, cobalt and iron bis(dicarbollides)) with amine and carboxylic acids which are derived from cholesterol. Stable liposomal formulations, on the basis of synthesized boron-containing lipids, hydrogenated soybean l -α-phosphatidylcholine and (HSPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) as excipients, were prepared and then characterized by dynamic light scattering (DLS) that revealed the formation of particles to be smaller than 200 nm in diameter. The resulting liposomal formulations showed moderate to excellent loading and entrapment efficiency, thus justifying the design of the compounds to fit in the lipid bilayer and ensuring ease of in vivo use for future application. The liposomal formulations based on cobalt and iron bis(dicarbollide)-based lipids were found to be nontoxic against both human breast normal epithelial cells MCF-10A and human breast cancer cells MCF-7.     

The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.     

Optical spectra of anionic boron cluster compounds and their utilization for photometric detection

The article presents first collection of UV-vis absorption spectra of purely synthetic boron cluster compounds. Single-cage compounds have at least 11 cluster atoms; cobaltadicarboranes consists of 2 substituted 11-vertex bis(dicarbollide) clusters sandwiching the central cobalt atom. Spectrum of any of 18 investigated compounds has absorption maximum between 200 and 210 nm; its molar extinction coefficient is of the order of 10(3)-10(4)L/molcm. Second maximum exists in a spectrum of a single-cage compound if its exo-skeletal substituent absorbs UV-light above 200 nm. Spectra of cobaltadicarbaboranes both bridged and unbridged have pronounced second maxima between 270 and 300 nm. Their molar extinction coefficients range from 10(4) to 10(5)L/molcm. First light absorption minimum is close to 254 nm in spectra with two and more absorption maxima. Several correlations are derived between structure of investigated compounds and their UV-vis absorption spectra.     

New boron-containing bacteriochlorin <Emphasis Type="Italic">p</Emphasis> cycloimide conjugate

A conjugate of the bacteriochlorophyll a derivative with the cobalt bis(dicarbollide) anion [3,3′-Co(1,2-C₂B₉H₁₁)₂]⁻ was synthesized.     

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.     

Theoretical study of nonlinear optical properties of cobalt bis (dicarbollide) derivatives: the effect of substituents

In the present work, molecular first-order hyperpolarizability (\(\beta _{\mathrm{tot}}\)) and dipole moment (d) are obtained at B3LYP/6–31G(d,p) level of theory by coupled perturbed Hartree–Fock method within the static approach. The investigated molecules are a series of substituted cobalt bis (dicarbollide) derivatives: Hydrogens bonded to the two carbon atoms are replaced by acceptor and donor electron substituents. Correlations between the Hammett electronic parameters of the substituents and the molecular properties are tested. Among them, the named push–pull compounds produced the largest calculated values of \(\beta _{\mathrm{tot}}\) and d. The UV–Vis spectra are reported for all studied compounds.     

Strontium and cesium extraction into hydrocarbons using alkyl cobalt dicarbollide and polyethylene glycols

The extraction of strontium and cesium ions from high ionic strength acid, base, and salt solutions into an organic extractant consisting of alkyl cobalt dicarbollide and polyethylene glycol (PEG) in diethylbenzene was investigated. Adding hexaethylene glycol or PEG-400 improved the strontium extraction ≥100-fold, while cesium extraction was decreased at high PEG concentrations. The extractions are rapid and selective, even in the presence of molar concentrations of sodium ion, suggesting that alkyl cobalt dicarbollide extractants are useful for the treatment of alkaline nuclear wastes. A method for the synthesis of tetra-n-hexyl(cobalt dicarbollide) is described.