Preparation of dendritic carboranyl glycoconjugates as potential anticancer therapeutics.

A series of carborane-appended glycoconjugates containing three and six glucose and galactose moieties have been synthesized via Cu(i)-catalyzed azide-alkyne [3 + 2] click cycloaddition reaction. The carboranyl glycoconjugates containing three glucose and galactose moieties were found to be partially water soluble whereas increasing the number to six made them completely water soluble. The evaluation of cytotoxicities and IC50 values of newly synthesized carboranyl glycoconjugates was carried out using two cancerous cell lines (MCF-7 breast cancer cells and A431 skin cancer cells) and one normal cell line (HaCaT skin epidermal cell line). All carboranyl glycoconjugates showed higher cytotoxicities towards cancerous cell lines than the normal cell line. Carboranyl glycoconjugates containing three glucose and galactose moieties (compounds 15 and 17) were found to be more cytotoxic than the glycoconjugates containing six glucose and galactose moieties (compounds 19 and 21). Moreover, administration of 100 µM concentrations of compounds 15 and 17 inhibited up to 83% of MCF-7 breast cancer cells and up to 79% A431 skin cancer cells. However, administration of similar concentrations of carboranyl glycoconjugates could inhibit only up to 35-45% of HaCaT normal epidermal cells. Thus, due to the higher cytotoxicities of dendritic carboranyl glycoconjugates towards cancer cells over healthy cells, they could potentially be useful for bimodal treatment of cancer such as chemotherapy agents and boron neutron capture therapy (BNCT) agents as well.

New classes of carborane-appended 5-thio-D-glucopyranose derivatives.

A series of carborane-appended 5-thio-D-glucopyranose (5-TDGP) derivatives containing one to two 5-TDGP moieties were synthesized via click cycloaddition reaction as well as following the traditional methods. Among the carboranyl-5-TDGP derivatives, the decapitated nido-carboranyl derivative 18 was found to be highly water-soluble and therefore its preliminary biodistribution study was conducted. A comparative biological evaluation of 18 versus its carboranyl-D-glucopyranose analog 19 with human hepatocellular carcinoma cells (SK-Hep1) indicated 5-TDGP to be a better boron carrier than normal D-glucopyranose. The carboranyl-5-TDGP 18 showed a nearly two fold increase in cellular boron accumulation than carboranyl-D-glucopyranose analog 19 over a period of 2 h. The accumulation of both 18 and 19 was found to occur in a temperature dependent manner. The higher accumulation of 18 suggested excellent promise for it to be a candidate for further evaluation as a future BNCT agent.

Enhanced π-conjugation and emission via icosahedral carboranes: synthetic and spectroscopic investigation.

The ability of ortho-, meta- and para-carboranes to enhance the emission intensity has been compared. For this purpose a series of carborane-appended 1,3,5-triphenylbenzene (TB) and 1,3,5- tris(biphenyl-4-yl)benzene (TBB) containing three ortho-, meta- and para-carborane clusters directly attached to the conjugated cores have been synthesized employing Suzuki, Heck, and trimerization reactions. The incorporation of the icosahedral carboranes was associated with a red shift in the UV absorption spectrum of up to 13 nm as well as enhancements of the emission intensities of up to 154%. The presence of ortho-carboranes showed the maximum red shift in the UV spectrum whereas the maximum enhancement of the emission intensity was observed in the presence of meta-carborane clusters. The order of π-conjugation extension is found to be ortho > meta ≈ para. A comparative thermal analysis indicated o-carborane-appended trimers to be the most thermally stable in the series. Proton NMR spectra of reported carborane-appended trimers indicated that ortho- and meta-carborane cages have benzenelike characteristics.

Carboranylpyrroles: a synthetic investigation.

The unusual reactivity of carborane mono- and dialdehydes with pyrroles in the presence of acid catalysts leads to the formation of a new class of carboranyl mono- and dipyrro derivatives.

"Click" synthesis and properties of carborane-appended large dendrimers.

Large dendrimers, noted G(n)-3(n+2)cage, containing 3(n+2) o-carborane cluster cages MeC(2)B(10)H(10) at their peripheries (n = number of generation noted G(n)) have been synthesized by Huisgen-type azide alkyne Cu(I)-catalyzed dipolar "click" cycloaddition reactions (CuAAC) between an o-carborane monomeric cluster containing an ethynyl group and arene-centered azido-terminated dendrimers G(n)-3(n+2)N(3) of generations 0, 1, and 2. Attempts to synthesize higher-generation dendrimers of this family yielded insoluble materials. The carborane dendrimers G(0)-9cage, G(1)-27cage, and G(2)-81cage have been characterized by (1)H, (13)C, (11)B NMR, elemental analysis, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy, and size exclusion chromatography (SEC) showing low polydispersities, dynamic light scattering (DLS) showing hydrodynamic diameters of 5.7 nm for the G(1)-27cage and the 12.9 nm for the G(2)-81cage. These dendrimers are extremely robust thermally, with 10% mass loss temperatures of 411 °C for the G(0)-9cage, 371 °C for the G(1)-27cage, and 392 °C for the G(2)-81cage. They all showed a strong absorption in the UV region peaking at 258 nm, whereas emission spectra of low intensities were observed between 280 and 480 nm.

Advances in the metallacarborane chemistry of f-block elements.

The role of carborane clusters in organometallic chemistry is diverse. A number of carborane cage systems such as C(2)B(4), C(2)B(9) and C(2)B(10) clusters have been extensively used for the synthesis of numerous metallacarboranes of s, p, d and f-block elements. An introduction to the chemistry of metallacarboranes is provided with an emphasis on the recent advances on the metallacarboranes of f-block elements.

Synthesis and properties of carborane-appended C(3)-symmetrical extended pi systems.

A series of C(3)-symmetric pi-conjugated compounds containing three to six o-carborane clusters have been synthesized by employing palladium-catalyzed Suzuki coupling reactions and palladium-catalyzed acetylation reactions, followed by silicon tetrachloride mediated trimerization reactions. Carborane-containing extended trimers were found to emit blue light. Incorporation of o-carborane clusters into extended pi-conjugated systems led to 22-70% enhancement of their relative fluorescence quantum yields. Decapitation of o-carborane clusters made these extended trimers water soluble, and their aqueous solutions were also found to be fluorescent, but with a reduced fluorescence intensity. The carborane-appended pi-conjugated compounds are found to be extremely thermally stable, and for some of these compounds only 10% mass loss occurred at temperatures close to 500 degrees C. The DSC thermograms of smaller C(cage)-appended trimers indicate the occurrence of solid-solid phase transitions.

Boron-enriched star-shaped molecule via cycloaddition reaction.

The facile synthesis of a thermally stable carborane appended symmetrical star-shaped molecule having six bulky o-carborane clusters on the periphery, thereby containing sixty boron atoms was accomplished via a cobalt-catalyzed [2+2+2] cycloaddition reaction.

Synthesis of a new class of carborane-containing star-shaped molecules via silicon tetrachloride promoted cyclotrimerization reactions.

Symmetrical star-shaped molecules with carborane clusters on the periphery have been synthesized in good yields via silicon tetrachloride mediated cyclotrimerization reactions of 9-benzyl derivatives of carboranes with acetyl group substitution on the benzene ring. Facile functionalization of these symmetrical core structures with 1-iodoheptane and trivinylchlorosilane produce compounds which could be used as liquid crystalline substances and precursors for synthesis of higher order carbosilane dendrons.

Serendipitously discovered diazomethane-mediated novel molecular rearrangements of norbornyl alpha-ketohemiketals.

[reaction: see text] Unprecedented molecular rearrangements during diazomethane-mediated reaction of norbornyl alpha-ketohemiketals leading to novel molecular entities are presented. A dramatic change in the reaction outcome was noted for five- and six-membered alpha-ketohemiketals: the former predominantly furnished rearranged bicyclic products involving migration of the gamma-alkoxy group, and the latter furnished the oxetane derivative as the major product. Interestingly, six-membered O-methyl-ketal yielded a product arising from the migration of the vicinal alkoxy group.

A rapid and stereoselective route to the trans-hydrindane ring system.

A short and stereoselective route to the trans-hydrindane derivative, a potential building block for the synthesis of steroidal and related molecules, was achieved by the operation of indium, tin, and ruthenium based reagents, starting from a tetrabromo norbornyl derivative.