Neutron Capture Therapy Agents Research Articles

Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging

Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM−1 s−1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.

Recent Progress in Fabrication and Application of BN Nanostructures and BN-Based Nanohybrids.

Due to its unique physical, chemical, and mechanical properties, such as a low specific density, large specific surface area, excellent thermal stability, oxidation resistance, low friction, good dispersion stability, enhanced adsorbing capacity, large interlayer shear force, and wide bandgap, hexagonal boron nitride (h-BN) nanostructures are of great interest in many fields. These include, but are not limited to, (i) heterogeneous catalysts, (ii) promising nanocarriers for targeted drug delivery to tumor cells and nanoparticles containing therapeutic agents to fight bacterial and fungal infections, (iii) reinforcing phases in metal, ceramics, and polymer matrix composites, (iv) additives to liquid lubricants, (v) substrates for surface enhanced Raman spectroscopy, (vi) agents for boron neutron capture therapy, (vii) water purifiers, (viii) gas and biological sensors, and (ix) quantum dots, single photon emitters, and heterostructures for electronic, plasmonic, optical, optoelectronic, semiconductor, and magnetic devices. All of these areas are developing rapidly. Thus, the goal of this review is to analyze the critical mass of knowledge and the current state-of-the-art in the field of BN-based nanomaterial fabrication and application based on their amazing properties.

Evaluation of 3-Borono-l-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent.

Although 4-borono-l-phenylalanine (4-BPA) is currently the only marketed agent available for boron neutron capture therapy (BNCT), its low water solubility raises concerns. In this study, we synthesized 3-borono-l-phenylalanine (3-BPA), a positional isomer of 4-BPA, with improved water solubility. We further evaluated its physicochemical properties, tumor accumulation, and biodistribution. The water solubility of 3-BPA was 125 g/L, which is more than 100 times higher than that of 4-BPA. Due to the high water solubility, we prepared the administration solution of 3-BPA without a solubilizer sugar, which is inevitably added to 4-BPA preparation and has adverse effects. In in vitro and in vivo experiments, boron accumulation in cancers after administration was statistically equivalent in both sugar-complexed 3-BPA and 4-BPA. Furthermore, the biodistribution of 3-BPA was comparable with that of sugar-complexed 3-BPA. Since 3-BPA has high water solubility and tumor targetability equivalent to 4-BPA, 3-BPA can replace 4-BPA in future BNCT.

China’s radiopharmaceuticals on expressway: 2014–2021

AbstractThis review provides an essential overview on the progress of rapidly-developing China’s radiopharmaceuticals in recent years (2014–2021). Our discussion reflects on efforts to develop potential, preclinical, and in-clinical radiopharmaceuticals including the following areas: (1) brain imaging agents, (2) cardiovascular imaging agents, (3) infection and inflammation imaging agents, (4) tumor radiopharmaceuticals, and (5) boron delivery agents (a class of radiopharmaceutical prodrug) for neutron capture therapy. Especially, the progress in basic research, including new radiolabeling methodology, is highlighted from a standpoint of radiopharmaceutical chemistry. Meanwhile, we briefly reflect on the recent major events related to radiopharmaceuticals along with the distribution of major R&D forces (universities, institutions, facilities, and companies), clinical study status, and national regulatory supports. We conclude with a brief commentary on remaining limitations and emerging opportunities for China’s radiopharmaceuticals.

Potential Theranostic Boron Neutron Capture Therapy Agents as Multimodal Radiopharmaceuticals.

Boron neutron capture therapy (BNCT) has been extant for decades and continues to be practiced in many centers around the globe. Most of the active clinical trials utilize boronophenylalanine as the drug containing boron atoms. The important aspect that has been added to the BNCT practice is the use of an F-18 radiolabeled analog for ascertaining targeting and monitoring follow-up studies. The recent widespread application of therapeutic radiopharmaceuticals, especially peptides (somatostatin analogs), prostate-specific antigen-binding ligands, or immunomolecules, offers the ambit for invention of new tumor-specific BNCT agents, especially for BNCT-susceptible tumors, that is, locoregional cancers such as head and neck cancer. Such BNCT agents, when radiolabeled, can enable simultaneous imaging and/or therapeutic applications (depending on the radionuclide used) through multimodal approaches. Development of boron-rich moieties such as sodium borocaptate and neutral carboranes combined with tumor-targeting moieties can lead to a new horizon in BNCT. The review covers various aspects of drug design, tumor targeting, and possible future radiopharmaceutical development for multimodal theranostic application in humans.

Electrochemical Cage Activation of Carboranes.

Carboranes are boron–carbon molecular clusters that possess unique properties, such as their icosahedron geometry, high boron content, and delocalized three‐dimensional aromaticity. These features render carboranes valuable building blocks for applications in supramolecular design, nanomaterials, optoelectronics, organometallic coordination chemistry, and as boron neutron capture therapy (BNCT) agents. Despite tremendous progress in this field, stoichiometric chemical redox reagents are largely required for the oxidative activation of carborane cages. In this context, electrosyntheses represent an alternative strategy for more sustainable molecular syntheses. It is only in recent few years that considerable progress has been made in electrochemical cage functionalization of carboranes, which are summarized in this Minireview. We anticipate that electrocatalysis will serve as an increasingly powerful stimulus within the current renaissance of carborane electrochemistry.

Gadolinium Neutron Capture Therapy (GdNCT) Agents from Molecular to Nano: Current Status and Perspectives.

157Gd (natural abundance = 15.7%) has the highest thermal neutron capture cross section (σ) of 254,000 barns (1 barn = 10–28 m2) among stable (nonradioactive) isotopes in the periodic table. Another stable isotope, 155Gd (natural abundance = 14.8%), also has a high σ value of 60,700 barns. These σ values are higher than that of 10B (3840 barns, natural abundance = 19.9%), which is currently used as a neutron-absorbing isotope for boron neutron capture therapy agents. Energetic particles such as electrons and γ-rays emitted from Gd-isotopes after neutron beam absorption kill cancer cells by damaging DNAs inside cancer-cell nuclei without damaging normal cells if Gd-chemicals are positioned in cancer cells. To date, various Gd-chemicals such as commercial Gd-chelates used as magnetic resonance imaging contrast agents, modified Gd-chelates, nanocomposites containing Gd-chelates, fullerenes containing Gd, and solid-state Gd-nanoparticles have been investigated as gadolinium neutron capture therapy (GdNCT) agents. All GdNCT agents had exhibited cancer-cell killing effects, and the degree of the effects depended on the GdNCT agents used. This confirms that GdNCT is a promising cancer therapeutic technique. However, the commercial Gd-chelates were observed to be inadequate in clinical use because of their low accumulation in cancer cells due to their extracellular and noncancer targeting properties and rapid excretion. The other GdNCT agents exhibited higher accumulation in cancer cells, compared to Gd-chelates; consequently, they demonstrated higher cancer-cell killing effects. However, they still displayed limitations such as poor specificity to cancer cells. Therefore, continuous efforts should be made to synthesize GdNCT agents suitable in clinical applications. Herein, the principle of GdNCT, current status of GdNCT agents, and general design strategy for GdNCT agents in clinical use are discussed and reviewed.

Oligonucleotide aptamers as novel cell-specific delivery agents for boron neutron capture therapy

Oligonucleotide aptamers seem to be promising delivery vehicles addressing boron compounds to tumour cells for boron neutron capture therapy (BNCT). Here, we report the first example of using 2'-F-RNA aptamer specific to human glioblastoma cells as a delivery agent for boron clusters, which provides cell internalisation sufficient for the BNCT model.

Synthesis of naphthalimide derivatives of closo‑dodecaborate and nido‑carborane

Methodologies for the synthesis of the first 3-nitro-1,8-naphthalimides bearing the nido‑carborane and closo‑dodecaborate moieties are reported. Series of boron containing 3-nitro-1,8-naphthalimides were synthesized by the reaction of 3-nitro-1,8-naphthalic anhydride with ammonium derivatives of nido‑carborane and closo‑dodecaborate anions. The nucleophilic ring-breakdown reaction of cyclic oxonium derivatives of nido‑carborane with the tertiary dimethylamino group of mitonafide led to the novel boron-enriched mitonafides. The synthesized compounds are of interest as potential agents for boron neutron capture therapy for cancer.

Boron delivery agents for boron neutron capture therapy

<p indent=0mm>Boron neutron capture therapy (BNCT) is a binary method of radiotherapy, which is based on the nuclear reaction that occurs when boron-10 is irradiated with thermal neutron to yield high linear energy transfer α particles and recoiling lithium-7 nuclei. These particles with high energy and short range can kill cancer cells which absorbed ¹⁰B while little damage to normal tissues. BNCT has experienced nearly <sc>90 years</sc> of development since it was first proposed in 1936, which is one of the most effective methods for the treatment of malignant glioma. One of the key factors for the success of BNCT is to find boron delivery agents with high targeting and high affinity to tumors. Currently, although there are various of boron delivery agents, the best compound recognized for BNCT is still boronophenylalanine (BPA), for it has little side effect and no chemistry toxicity. BPA can penetrate the BBB and cell membrane, so it owns higher relative biological effectiveness. BPA is the most widely used BNCT drug in the world, which was officially approved in Japan last year, and the therapeutic effect on glioma is without question. In the past few decades, in order to improve the efficacy of BNCT, significant effort has been devoted to developing new boron delivery agents that possess better uptake and favorable pharmacokinetic characteristics for clinical use. This review focuses on differents kinds of boron delivery agents developed over the past years, which can be divided into three generations. At present, the first generation of boron delivery agents has been banned for lacking of targeting. The second generation of boron delivery agents is the most mature of the clinical application, but there are some problems need to be solved, such as limited boron loading and individual uptake varies greatly. The third generation of boron delivery agents contains various of agents—The boron-containing amino acids and peptides, the boron-containing compound conjugated with nucleosides, porphyrin derivatives, and different types of nanomaterials, was introduced in detail in this review. The boron loading and targeting of the third generation of boron delivery agents have greatly increased, but most of them are still in the experimental stage, and the safety and effectiveness need to be further verified. The advantages and disadvantages of the three generation boron delivery agents were analyzed and compared. Meanwhile the limitations of the various boron delivery agents were discussed and summarized. Additionally, the prospect and bottleneck of clinical arpplication of these boron delivery agents was critically analyzed from different view of research institutions, pharmaceutical enterprises and government policy. And the corresponding solutions were proposed: (1) Expand the application scope of BPA and BSH; develop new drugs and expand the application fields of BNCT technology; (2) enhance the cooperation of enterprises, university and research institutions, and promote the clinical approval and application of BPA and BSH; (3) multi disciplines jointly overcome technical barriers and establish a perfect evaluation system of safety and effectiveness for BNCT. In summary, with the official approval of the Japanese accelerator BNCT treatment system, the application prospects of BNCT technology will be broad all over the world. The comprehensive research of BNCT technology will be promoted by enhancing the intercrossing and coalescence between subjects relative with BNCT, and new ideas will be inspired, all of which will promote the clinical application of BNCT technology, and that benefit patients.

Gadolinium delivery agents for neutron capture therapy

<p indent=0mm>Neutron capture therapy (NCT) is a binary form of radiation therapy that combines neutron irradiation with a tumor targeting agent labeled with a stable isotope having a high thermal neutron capture cross section and yielding charged particle reaction products after neutron capture. At present, NCT has largely, but not exclusively, focused on the use of boron-10 as the target nuclide. Gadolinium neutron capture therapy (Gd-NCT) is an alternative and supplementary method of boron neutron capture therapy (BNCT). Gd-157, which has the largest cross-section (254000 barn) of thermal neutrons of all stable isotopes, is the most effective isotope in terms of neutron capture. The Gd neutron capture reaction, ¹⁵⁷Gd(n, γ)¹⁵⁸Gd, provokes complicated nuclear decay transitions that generate low linear energy transfer (LET) gamma photons and the emission of high LET conversion electrons and Auger electrons. Therefore, Gd is considered to be highly suitable for the absorption of thermal neutrons in the NCT reaction. Another advantage of Gd-NCT is Gd³⁺ has a longer retention time and can thus be tracked by means of magnetic resonance imaging (MRI) methods. Currently, Gd(III) based MRI contrast agents are most commonly used in clinical practice. However, due to lack of appropriate tumor-selective Gd agents, the Gd-NCT concept has not yet been clinically tested. For a successful neutron capture therapy, a target nuclide delivery system with high therapeutic efficiency and low adverse effects is crucial. Three major classes Gd delivery agents have been developed so far, small molecule chelates of Gd, nano- delivery agents, and Gd-B dual delivery agents. In the first trial of Gd-NCT, commercially available MRI contrast agents composed of Gd-chelating compounds were used as Gd delivery agents. However, due to the insufficient number of tumor cell nuclei incorporating Gd, efficacy of small molecule chelates of Gd as Gd-NCT delivery agents is generally low. In recent years, with the rapid development of nanotechnology, nanomaterials have been widely employed as carriers for cancer theranostics. A variety of Gd-based nanomaterials have been developed for pre-clinical trials of NCT. Majority of them are constructed by incorporating commercially available MRI contrast agents in biocompatible nanomaterials (liposomes, albumin, and micelles), or employing Gd based nanoparticles with their unique physiochemical properties. While nano-Gd delivery agents have proved to be a promising strategy in Gd-NCT, it is also possible to integrate of both Gd and B in one delivery agent. The design of many Gd-NCT agents to date has focused on combined BNCT and Gd-NCT agents in order to maximise cytotoxicity from the combined effects or to use the B component for NCT and the Gd component as a MRI imaging agent. This paper highlights the recent advances in Gd selective and efficient delivery methods and the preclinical outcome of Gd-NCT, both advantages and disadvantages of various Gd delivery agents were addressed. Finally, we offered our perspectives on the challenges and future development of Gd delivery agents for Gd-NCT.

Synthesis, characterization, and in vitro assessment of cytotoxicity for novel azaheterocyclic nido-carboranes – Candidates in agents for boron neutron capture therapy (BNCT) of cancer

A series of novel water-soluble azaheterocyclic derivatives of nido-carborane bearing quinoxaline, 2H-imidazole or 1,2,4-triazine moieties were first synthesized in 82–91% yields. The structures of these boron-enriched compounds were confirmed by the data of NMR, IR spectroscopy, and mass spectrometry. To access the toxicity level for these organoboron compounds, the cytotoxicity indexes (IC50) were determined using by the MTT test on both human glioblastoma cell A-172 (IC50 = 150–243 μM) and human embryonic lung cells (IC50 = 424–944 μM) lines. The obtained preliminary results from in vitro analysis enable the synthesized water-soluble azaheterocyclic carboranes to be considered as challenging candidates in the design of agents for boron-neutron capture therapy (BNCT) of malignant tumors.

Boron and Gadolinium Loaded Fe3O4 Nanocarriers for Potential Application in Neutron Capture Therapy.

In this article, a novel method of simultaneous carborane- and gadolinium-containing compounds as efficient agents for neutron capture therapy (NCT) delivery via magnetic nanocarriers is presented. The presence of both Gd and B increases the efficiency of NCT and using nanocarriers enhances selectivity. These factors make NCT not only efficient, but also safe. Superparamagnetic Fe3O4 nanoparticles were treated with silane and then the polyelectrolytic layer was formed for further immobilization of NCT agents. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), ultraviolet–visible (UV-Vis) and Mössbauer spectroscopies, dynamic light scattering (DLS), scanning electron microscopy (SEM), vibrating-sample magnetometry (VSM) were applied for the characterization of the chemical and element composition, structure, morphology and magnetic properties of nanocarriers. The cytotoxicity effect was evaluated on different cell lines: BxPC-3, PC-3 MCF-7, HepG2 and L929, human skin fibroblasts as normal cells. average size of nanoparticles is 110 nm; magnetization at 1T and coercivity is 43.1 emu/g and 8.1, respectively; the amount of B is 0.077 mg/g and the amount of Gd is 0.632 mg/g. Successful immobilization of NCT agents, their low cytotoxicity against normal cells and selective cytotoxicity against cancer cells as well as the superparamagnetic properties of nanocarriers were confirmed by analyses above.

Synthesis of carborane-containing carbonates via CO2 addition to epoxides

A new method for the synthesis of carborane-containing carbonates by the reaction of CO2 with the corresponding epoxides was developed. The reaction can be facilitated by an additional hydroxyl group in the catalyst. The crystal structure of 1-phenyl-2-(1,3-dioxolan-2-onylmethyl)-C2B10H10 was determined by single crystal X-ray diffraction. The carborane-containing carbonates can be considered as precursors for the synthesis of advanced heat- and impact-resistant polycarbonates and agents for boron neutron capture therapy.

Original boron cluster covalent with poly-zwitterionic BODIPYs for boron neutron capture therapy agent

Currently, boron neutron capture therapy（BNCT） is the most innovative and promising highly selective targeted radiotherapy for cancer. Therefore, this paper designed and synthesized two kinds of boron-polymers, wrapped in the same fluorophore -BODIPYs, as fluorescent targeting markers for rapid, accurate, real-time, and inexpensive detection of boron-containing drugs. The spherical polymer o-carborane (PBC) in different polar solvents, the ultraviolet maximum absorption wavelength is in the range of 530–545 nm. The maximum ultraviolet absorption wavelength of PBD is in the range of 440–520 nm. The fluorescence spectra of the two boron-polymer are very similar, and the maximum emission wavelength is concentrated in the range of 550–560 nm. In terms of cytotoxicity and in vitro cell imaging, the in vitro biological toxicity evaluation of the two boron-polymer reached the expected high level, especially the cytotoxic concentration of PBD reached 1.347 ± 0.033 μM, which was higher than the 2.829 ± 0.351 μM of PBC. By transmission electron microscopy, it was found that the two terminal zwitterions of BODIPY polymer tightly wrapped boron clusters to form small particle nanoclusters. The imaging of the two boron-polymers was tested in the Hera cell lines of low, medium, and high densities. The in vitro study results revealed high levels of accumulation in HeLa cells with higher cytotoxicity and boron uptake compared to L-boron-phenylalanine (BPA). In vivo imaging, large number of borane polymers were observed to accumulate in the subcutaneous tumor sites of mice over time, indicating that it has high selectivity and high aggregation.

Improvement of Water Solubility of Mercaptoundecahydrododecaborate (BSH)-Peptides by Conjugating with Ethylene Glycol Linker and Interaction with Cyclodextrin

We previously developed a conjugate consisting of 10B cluster BSH and tri-arginine peptide (BSH-3R). This could potentially be used as a boron agent for boron neutron capture therapy; however, it possesses poor water solubility and thus needs to be improved for use as medicine. In this study, we devised several means of improving the water solubility of BSH-3R. As one of them, we used cyclodextrin (CD), which was expected to improve the water solubility resulting from interaction of the BSH-3R with CD. We evaluated the solubility of BSH-3R in aqueous CD solution by using reverse-phase high-performance liquid chromatography. As we expected, the solubility of BSH-3R was increased in a manner dependent on the addition of β-CD and γ-CD in aqueous solution. Furthermore, we synthesized BSH conjugated to oligoarginine having various chain lengths (BSH-nR) and BSH-3R with ethylene glycol linkers introduced between BSH and 3R (BSH-nEg-3R). The water solubility of these BSH peptides was also evaluated and the results showed that the introduction of nEg to BSH-3R markedly improved the water solubility. Furthermore, we found that the water solubility of these peptides can be further improved by also applying CD.

Carboxyboranylamino ethanol: unprecedented discovery of boron agents for neutron capture therapy in cancer treatment.

Carboxyboranylamino ethanol (Me2N(BH2CO2H)CH2CH2OH, 1) was prepared in 75.0% yield by an amine-exchange reaction. Compound 1 shows lower cytotoxicity and higher anti-tumor efficacy in vitro towards the SCCVII cell line in comparison with 4-borono-L-phenylalanine (BPA) and methyl 2-hydroxyl-5-(1'-ortho-carbonylmethyl-1',2',3'-triazol-4'-yl)-benzonate (2). The bio-enhancement is interpreted using molecular docking calculations.

Ru(ii) and Ir(iii) phenanthroline-based photosensitisers bearingo-carborane: PDT agents with boron carriers for potential BNCT

Four novel transition metal-carborane photosensitisers were prepared by Sonogashira cross-coupling of 1-(4-ethynylbenzyl)-2-methyl-o-carborane (A-CB) with halogenated Ru(ii)- or Ir(iii)-phenanthroline complexes. The resulting boron-rich complexes with one (RuCB and IrCB) or two carborane cages (RuCB2 and IrCB2) were spectroscopically characterised, and their photophysical properties investigated. RuCB displayed the most attractive photophysical properties in solution (λem 635 nm, τT 2.53 μs, and φp 20.4%). Nanosecond time-resolved transient absorption studies were used to explore the 3MLCT nature of the triplet excited states, and the highest singlet oxygen quantum yields (ΦΔ) were obtained for the mono-carborane-phenanthroline complexes (RuCB: 52% and IrCB: 25%). None of the complexes produce dark toxicity in SKBR-3 cells after incubation under photodynamic therapy (PDT) conditions. Remarkably, mono-carboranes RuCB and IrCB were the best internalised by the SKBR-3 cells, demonstrating the first examples of tris-bidentate transition metal-carborane complexes acting as triplet photosensitisers for PDT with a high photoactivity; RuCB or IrCB killed ∼50% of SKBR-3 cells at 10 μM after irradiation. Therefore, the high-boron content and the photoactive properties of these photosensitisers make them potential candidates as dual anti-cancer agents for PDT and Boron Neutron Capture Therapy (BNCT).

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties.

Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, the closo-dodecaborate anion represents a high-boron-containing residue with remarkable chemical stability and low toxicity, and is suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5′-, 3′-, or both terminal positions of DNA, RNA, 2′-O-Me RNA, and 2′-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3′-end of all oligomers stabilized their complementary complexes, whereas analogous 5′-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2′-O-methyl and 2′-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized the DNA/DNA duplex but gave a strong stabilization of the duplex with an RNA target. According to circular dichroism spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from the B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

Recent Advances in Transition Metal-Catalyzed Selective B-H Functionalization of o-Carboranes

Abstract Carboranes are a class of carbon-boron molecular clusters, possessing extraordinary characteristics including three-dimensional aromaticity conjugated by σ-bonds, icosahedral geometry and inherent robustness. They are finding growing applications as valuable building blocks in boron neutron capture therapy agents, pharmacophores, nanomaterials, optoelectronic, organometallic/coordination chemistry and more. Therefore, the effective and controlled functionalization of carboranes has attracted enormous research interests, particularly in regio- and enantio-selective cage BH derivatization among ten chemically similar BH vertices of o-carboranes. Only in the recent few years, significant progress has been made in transition metal catalyzed vertex-specific BH functionalization. This review summarizes recent advances in this research realm.