Volume 87, Issue 2

Cancer is one of the leading causes of death; with it may different types, it kills thousands of people every day. Various types of treatment have been developed to treat and cure cancer. Nanotechnology has emerged as one of the most fruitful areas of science in cancer treatment and the nanomaterials are considered as a medical boon for the diagnosis, treatment and prevention of cancer. The major approaches of nanotechnology in tumor treatment include the development of nanoparticles with less or no tissue-resistance, their biocompatibility, ability as nanocarriers for drug delivery, and enhanced energy deposition in tissue with or without the external influence of microwave, light, magnet, etc. This review presents some of the recent developments in the use of nanoparticles as adjuncts to boron and gadolinium containing compounds in boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT) along with the latest developments in the area of boron nanotubes (BNTs), gadolinium oxide, boron nitride nanotubes (BNNTs) and the boron agent itself.

Reactions between the arachno -6,9-C 2 B 8 H 14 dicarbaborane and acyl chlorides, RCOCl, in the presence of amine bases in CH 2 Cl 2 , followed by acidification with conc. H 2 SO 4 at 0 °C, generate in high yields a series of neutral alkyl and aryl tricarbollides of structure 8-R- nido -7,8,9-C 3 B 8 H 11 (where R=alkyls and aryls). These skeletal alkylcarbonation (SAC) reactions are consistent with an aldol-type condensation between the RCO group and open-face dicarbaborane hydrogen atoms, which is associated with the insertion of the acyl chloride RC unit into the structure under elimination of three extra hydrogen atoms as H 2 O and HCl. The reactions thus result in an effective cross-coupling between R and the tricarbollide cage. High-temperature reactions between 8-Ar- nido -7,8,9-C 3 B 8 H 11 (where Ar=Ph, 1-C 10 H 7 , and 2-C 10 H 7 ) compounds and [CpFe(CO) 2 ] 2 produced the first types of monoaryl substituted twelve-vertex ferratricarbollide complexes of general constitution [1-(CpFe)- closo -ArC 3 B 8 H 10 ] with three different arrangements of cluster carbon vertexes. The Fe-complexation is accompanied by extensive rearrangement of the cluster carbon atoms over the twelve-vertex cage and the complexes isolated can be regarded as ferrocene analogues.

Diaryl-substituted carboranes, as a new class of HIF-1α inhibitors, were synthesized from the corresponding diaryl-substituted alkynes by decaborane coupling. The microwave-irradiated conditions with a combination of N,N -dimethylaniline and chlorobenzene were effective to obtain the diaryl-substituted carboranes in good to high yields. Among the compounds synthesized, compounds 1a and 1d showed significant inhibition of HIF-1 mediated transcriptional activity under hypoxia. Both compounds similarly suppressed hypoxia-induced HIF-1α accumulation in a concentration-dependent manner without affecting HIF-1α mRNA expression.

Boric acid, H 3 BO 3 , is a weak acid and at physiological pH is in the form of an uncharged small molecule. Behaving as a Lewis acid, it forms complexes with amino- and hydroxy acids, carbohydrates, nucleotides and vitamins through electron donor-acceptor interactions. These interactions are believed to be beneficial for human health. Synthetic bis- chelate complexes of boric acid with organic biomolecules are therefore considered for nutritional and/or pharmaceutical applications. The use of boric acid for BNCT has gained attention due to the short biological half-life, solubility, plasma circulation and the non-selective soft tissue accumulation properties of this simple molecule. Complexation of boric acid with sugars is of particular importance in understanding the role of boron as a carrier for nucleotides and carbohydrates. A potential and catalytic role of boric acid in peptide and nucleic acid synthesis and in the stabilization of sugar molecules by acting as a complexing agent have been demonstrated. Its possible role as a phosphorylation chaperone in a prebiotic world has been recently suggested. This contribution reviews the highlights in the physiologic, therapeutic and prebiotic significance of boric acid in the last decade.

Dicarba- closo -dodecaboranes(12) (C 2 B 10 H 12 , carbaboranes) are highly hydrophobic and stable icosahedral carbon-containing boron clusters. The cage framework of these clusters can be modified with a variety of substituents, both at the carbon and at the boron atoms. Substituted carbaboranes are of interest in medicine as boron neutron capture therapy (BNCT) agents or as pharmacophores. High and selective accumulation in tumour cells is an important requirement for a BNCT agent and is achieved by incorporating boron-rich, water-soluble carbaborane derivatives into breast tumour-selective modified neuropeptide Y, [F 7 , P 34 ]-NPY. Preliminary studies showed that the receptor binding affinity and signal transduction of the boron-modified peptides were very well retained. Use of carbaboranes as pharmacophores was shown by replacement of Bpa 32 (Bpa=benzoylphenylalanine) in the reduced-size NPY analogue [Pro 30 , Nle 31 , Bpa 32 , Leu 34 ]-NPY 28–36 by ortho -carbaboranyl propanoic acid. The inclusion of the carbaborane derivative resulted in a short NPY agonist with an interesting hY 2 R/hY 4 R preference. This might be a promising approach in the field of anti-obesity drug development.

Boron clusters have been employed successfully as constituents in bioactive substances. In this review, the perspectives of boron clusters for drug design and problems to be solved for a broader application are discussed, and a list of actions is given for overcoming the problems.

Diboron reagents can be activated both, from a metal or free-metal context, and consequently the addition of boryl units to unsaturated substrates proceeds sometimes with complementary selectivity. We highlight here the power of boron chemistry to functionalize molecules and provide new routes towards challenging compounds.

Thermolysis of an in situ generated intermediate [(Cp*Ta) 2 (BH 3 ) 2 Cl 2 ], 1 generated from the reaction of [Cp*TaCl 4 ], (Cp* = η 5 -C 5 Me 5 ) and [LiBH 4 ·thf], in presence of [Ru 3 (CO) 12 ] yielded pileo -[Cp*TaCl(μ-Cl)-B 2 H 4 Ru 3 (CO) 8 ], 2 having two electrons fewer than seven pairs required for the observed square pyramidal geometry. Cluster 2 is the first example of an unsaturated cluster comprising early and late transition metals in a square pyramid core. This reaction also yielded [(Cp*Ta) 2 (B 2 H 6 )(B 2 H 4 Cl 2 )], 3 as a by-product. In addition, the reaction of [Cp*MoCl 4 ] (Cp* = η 5 -C 5 Me 5 ) with [LiBH 4 .thf] in presence of excess [MeI] at mild condition led to the isolation of periodinated dimolybdatetraborane [(Cp*Mo) 2 B 4 H 3 I 5 ], 4 that hints a possible existence of [(Cp*Mo) 2 B 4 H 8 ]. After the isolation of periodinated 4 , we extended this chemistry towards the late transition metallaborane [(Cp*Rh) 3 B 4 H 4 ], 5 using [PtBr 2 ] as brominating source. Although all the attempts to isolate perbrominated rhodaborane failed, we have isolated partially brominated rhodaborane clusters [(Cp*Rh) 3 (BH)-(BBr) 3 ], 6 and [(Cp*Rh) 3 (BH) 3 (BBr)], 7 . All the compounds were characterized by IR and 1 H, 11 B and 13 C NMR spectroscopy in solution, and the solid-state structures of 2 , 4 and 6 were established by crystallographic analysis.

The nonenzymatic synthesis of nucleic acids, in particular, RNA, and the template-directed synthesis of artificial organic molecules, such as macrocycles, catenanes and rotaxanes, have both undergone significant development since the last half of the 20 th century. The intersection of these two fields affords insights into how template effects can lead to information copying and storage at the molecular level. Mechanistic examples of model template-directed RNA replication experiments as well as those for totally artificial organic template-directed syntheses will be discussed. The fact that templates typically bind to their reacted products more tightly than their unreacted substrates may be a mechanistic feature necessary to store information in the form of nucleic acids. Understanding the mechanisms of nonenzymatic RNA synthesis is not only essential for testing the RNA world hypothesis in the context of the origin of life on Earth and other planetary bodies, but may one day afford chemists the insights to construct their own artificial molecular replicators.