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Multi-disciplinary approaches to problem solving are needed given the increasing complexity of fundamental scientific questions. This dissertation undertakes a holistic approach to research and tackles challenges spanning the biology, chemistry, and materials interface. The central theme for most projects involves applying inorganic and main group chemistry to develop new bioconjugation strategies or polymerization methodologies to access novel materials. Chapter One describes efforts in understanding the effects of trehalose polymers towards protein stabilization. The stabilization capability of polymers made from a set of styrenyl-based trehalose monomer regioisomers were studied. Polymers of each trehalose monomer regioisomer and one polymer which contained all three isomers combined were synthesized. All polymer regioisomers stabilized insulin to a similar degree towards agitation and heat stress.Chapter Two details the initial discovery that icosahedral boron-rich cluster compounds of the type B12(OR12)—where “R” can be any alkyl or aryl group— could be utilized as strong one-electron photooxidants thereby initiating the polymerization of olefins. The perfunctionalized clusters are able to initiate polymerization of a range of styrene substrates under blue LED irradiation. Also demonstrated, is the visible light initiated, metal free cationic polymerization of isobutylene into poly(isobutylene).Chapter Three introduces a new class of carborane-based chain-transfer agents (CTA’s) to be used in reversible addition-fragmentation chain-transfer (RAFT) polymerization. The carborane-based CTA’s mediate the controlled polymerization of monomers such as styrene, N-isopropylacrylamide, and methyl acrylate to produce monodisperse carborane terminated polymers. The carborane-based scaffold, appended on the polymer chain end, serves as a general 1H NMR spectroscopic handle used to elucidate polymer molecular weight. Binding of carborane into the hydrophobic cavity of β-cyclodextrin was demonstrated by isothermal titration calorimetry thereby validating its potential use as an affinity label. The carborane RAFT agents also act as Raman active probes.Chapter Four explores the reactivity of gold(III) organometallic complexes in the context of bioconjugation chemistry. The gold(III) organometallic complexes mediated the conjugation of small molecule substrates which included heterocycles, an anti-cancer drug, biotin, and low molecular weight PEG to cysteine residues on biomolecules. The bioconjugation reactions proceeded rapidly, with high efficiency, and in a broad pH range.

Carboranes are boron-carbon clusters with important applications in fields of materials, catalysis, pharmaceuticals, etc. However, the non-covalent interactions that could determine the solid-state structures and properties of such boron clusters have been rarely investigated. Herein, inspired by the coordinate bond in metallacarborane or ferrocene, the boron cluster-based non-covalent interaction (denoted as cage-···cage- interaction) between two nido-carborane clusters was successfully realized by using a pyridinium-based molecular barrier. The X-ray diffraction studies uncover that the cage-···cage- interaction has a contacting dis-tance of 5.4-7.0 Å from centroid to centroid in the systems reported here. Theoretical calculations validate the formation of the non-covalent interaction and disclose its repulsive bonding nature that is overcome thanks to the positively charged pyridinium-based framework. Interestingly, such bulk crystalline materials containing the cage-···cage- interaction show relevant properties such as full-color absorption in the visible light range and important photothermal effect, which are absent for the control com-pound without carboranes. This study may offer fundamental insights into the boron cluster-based non-covalent interactions and open a new research avenue to rationally design boron cluster-based materials This work has been supported by the Ministerio de Economía y Competitividad (MINECO) of Spain (Projects CTQ2017-85341-P, PID2019-106830GB-I00, PID2020-113711GB-I00, and MDM-2017-0767) and the Generalitat de Catalunya (projects 2017SGR39 and 2017SGR348). Excellent service by the Supercomputer center of the Consorci de Serveis Universitaris de Catalunya (CSUC) is gratefully acknowledged. The authors also gratefully acknowledge the financial support from NSFC (21820102004, 21531004, and 91961104)

ABSTRACT OF THE DISSERTATIONNeutral and Anionic Carboranes as Electronically and Sterically Diverse Phosphine SubstituentsbyChristopher Alexander LugoDoctor of Philosophy, Graduate Program in ChemistryUniversity of California, Riverside, June 2017Dr. Vincent Lavallo, ChairpersonThe chemistry of carboranes has expanded greatly since their discovery in the 1960’s. Displaying 3D aromaticity, superior thermal and chemical stability, and facile tunability, these molecules have seen a wide range of applications but little has been said for their potential as transition metal catalysts. We sought to remedy this rift by 1) constructing a library of ligands that integrate carboranes into phosphines as R-group substituents, 2) ligating the ligands to an array of transition metal centers, and 3) surveying the reactivity of the isolated metal complexes. By substituting the inherently bulky ortho-carborane with a terphenyl moiety at the C-2 position, and a phosphine at the C-1 position, a massive ligand was created. The donor and steric properties were analyzed via a rhodium carbonyl complex. A nido version of the above terphenyl carboranyl phosphine was also synthesized and its behavior with iridium was investigated. Through preparation of phosphines of the anionic 12 and 10-vertex carboranes, rhodium carbonyl complexes were synthesized to quantitatively assess their donor properties. Through utilization of a carboranylphosphino iron complex, the ability to cyclically trimerize methylacrylate has been demonstrated through the isolation a phosphonium enolate species. Amongst the vast library of monoanionic carboranyl phosphines there are none containing a dianionic phosphine. Using PCl3 as a launch pad, a variety of monoanionic and dianionic ligands were systematically prepared with ranging electronic and steric profiles.

The preparation of a molecule with two alkyl‐tethered silylium‐ion sites from the corresponding bis(hydrosilanes) by two‐fold hydride abstraction is reported. The length of the conformationally flexible alkyl bridge is crucial as otherwise the hydride abstraction stops at the stage of a cyclic bissilylated hydronium ion. With an ethylene tether, the open form of the hydronium‐ion intermediate is energetically accessible and engages in another hydride abstraction. The resulting bis(silylium) ion has been NMR spectroscopically and structurally characterized. Related systems based on rigid naphthalen‐n,m‐diyl platforms can only be converted into the dications when the positively charged silylium‐ion units are remote from each other (1,8 versus 1,5 and 2,6)., Supercharged: A single silylium ion is hard to handle but what about two of these superelectrophiles in one molecule in close proximity? Depending on the distance between these Lewis acidic sites, such a previously elusive bidentate Lewis acid can be accessible, characterized, and stored at room temperature.

o ‐Carborane, a cluster compound containing boron and adjacent carbon atoms, displays intriguing luminescent properties. Recently, compounds containing o ‐carborane units were found to show suppressed aggregation‐induced quenching and intense solid‐state emission; they also show potential for the development of stimuli‐responsive luminochromic materials. In this Minireview, we introduce three kinds of fundamental photochemical properties: aggregation‐induced emission, twisted intramolecular charge transfer in crystals, and environment‐sensitive excimer formation in solids. Based on these properties, several types of luminochromism, such as thermos‐, vapo‐, and mechanochromism, have been discovered. Based mainly on results from recent studies, we illustrate these mechanisms as well as unique luminescent behaviors of o ‐carborane derivatives.

Raman spectroscopic measurements and theoretical calculation revealed that the Raman bands corresponding to the B–H stretching vibrations of two types of simple icosahedral boron clusters, ortho-carborane 3 and closo-dodecaborate 4 appeared at approximately 2450–2700 cm−1, and did not overlap with those of cellular components. Although ortho-carborane 3 possesses a possible property as a Raman probe, it was difficult to measure Raman imaging in the cell due to its poor water solubility. In fact, ortho-carborane derivative 6, which internally has an alkyne moiety, exhibited very weak Raman signals of the CC stretching and the B–H stretching vibrations were barely detected at a 400 ppm boron concentration in HeLa cells. In contrast, closo-dodecaborate derivatives such as BSH (5) were found to be a potential Raman imaging probe cluster for target molecules in the cell. BSH-conjugated cholesterol 7 (BSH-Chol) was synthesized and used in Raman imaging in cells. Raman imaging and spectral analysis revealed that BSH-based Raman tags provide a versatile platform for quantitative Raman imaging.

Bu çalışmada B6-nCnHn (n=0-6) serilerinin yapısal ve enerji özellikleri yoğunluk fonksiyonel teorisi kullanılarak araştırıldı. Adyabatik iyonizasyon potansiyeli (AIP), doğrudan iyonizasyon potansiyeli (VIP), adyabatik elektron ilgisi (AEA), doğrudan elektron ilgisi (VEA), doğrudan ayrılma enerjisi (VDE), HOMO-LUMO enerji aralığı (Eg) ve bağlanma enerjisi B3LYP/6-311++G** teori seviyesinde incelendi ve en kararlı izomerler tartışıldı. Yük dağılımı ve çekirdekten bağımsız kimyasal kayma analizleri de gerçekleştirildi. B2C4H4 and C6H6 serileri IP, EA ve Eg hesaplamaları sonucunda en kararlı seriler olarak bulunmuştur. Benzen tipi yapı BC5H5 (n=5) serisi için en kararlı isomer olarak bulunmuştur ve bu yapı benzen kadar aromatik olabilir., In this study, the structural and energetic properties of B6-nCnHn (n=0-6) series were investigated using Density Functional Theory (DFT) approach. Adiabatic ionization potential (AIP), vertical ionization potential (VIP), adiabatic electron affinity (AEA), vertical electron affinity (VEA), vertical detachment energy (VDE), HOMO-LUMO energy gap (Eg) and binding energy (Eb) have been investigated at the B3LYP/6-311++G** level of theory and discussed for the most stable isomers. Charge distribution and nucleus independent chemical shift (NICS) analysis were also performed. B2C4H4 and C6H6 series are the most stable among considered series by calculating ionization potentials (IPs), electron affinities (EAs) and Eg. The benzene-like structure is found to be the most stable isomer for n=5 (BC5H5), and it can be as aromatic as benzene.

A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine N-nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Further nucleophilic substitution of their remaining chlorine atoms with propargylamine in DMF led to morpholine- and diethylamine-functionalized monopropargylamine cage complexes, the molecules of which contain the single terminal C≡C bond. Their “click” 1,3-cycloaddition reactions in toluene with ortho-carborane-(1)-methylazide catalyzed by copper(II) acetate gave spacer-containing di- and tritopic iron(II) carboranoclatrochelates formed by a covalent linking between their different polyhedral(cage) fragments. The obtained complexes were characterized using elemental analysis, MALDI-TOF mass, UV-Vis, 1H, 1H{11B}, 11B, 11B{1H}, 19F{1H} and 13C{1H}-NMR spectra, and by a single crystal synchrotron X-ray diffraction experiment for the diethylamine-functionalized iron(II) carboranoclathrochelate. Its encapsulated iron(II) ion is situated almost in the center of the FeN6-coordination polyhedron possessing a geometry intermediate between a trigonal prism and a trigonal antiprism with a distortion angle φ of approximately 28°. Conformation of this hybrid molecule is strongly affected by its intramolecular dihydrogen bonding: a flexibility of the carborane-terminated ribbed substituent allowed the formation of numerous C–H…H–B intramolecular interactions. The H(C) atom of this carborane core also forms the intermolecular C–H…F–B interaction with an adjacent carboranoclathrochelate molecule. The N–H…N intermolecular interaction between the diethylamine group of one hybrid molecule and the heterocyclic five-membered 1H-[1,2,3]-triazolyl fragment of the second molecule of this type caused formation of H-bonded carboranoclathrochelate dimers in the X-rayed crystal.

Using the chelating C,C′‐bis(silylenyl)‐ortho‐dicarborane ligand, 1,2‐(RSi)2‐1,2‐C2B10H10 [R=PhC(NtBu)2], leads to the monoatomic zero‐valent Ge complex (“germylone”) 3. The redox non‐innocent character of the carborane scaffold has a drastic influence on the reactivity of 3 towards reductants and oxidants. Reduction of 3 with one molar equivalent of potassium naphthalenide (KC10H8) causes facile oxidation of Ge0 to GeI along with a two‐electron reduction of the C2B10 cluster core and subsequent GeI‐GeI coupling to form the dianionic bis(silylene)‐supported Ge2 complex 4. In contrast, oxidation of 3 with one molar equivalent of [Cp2Fe][B{C6H3(CF3)2}4] as a one‐electron oxidant furnishes the dicationic bis(silylene)‐supported Ge2 complex 5. The Ge0 atom in 3 acts as donor towards GeCl2 to form the trinuclear mixed‐valent Ge0→GeII←Ge0 complex 6, from which dechlorination with KC10H8 affords the neutral Ge2 complex 7 as a diradical species., The bis(silylenyl) ortho‐dicarborane‐supported zero‐valent Ge complex (germylone) 1 undergoes facile dimerization with Ge−Ge bond formation upon one‐electron oxidation and reduction to furnish the bis(silylene)‐supported dicationic and dianionic [GeI–GeI] complexes 2 and 3, respectively. A neutral complex 4 bearing a Ge2 2+ dumbbell embedded in a shell of two radical‐anionic di(silylenyl)dicarborane ligands could be synthesized.

Bis(carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 (n = 0, 1) were prepared by the reactions of the corresponding carboranyl acyl chlorides with ethylenediamine. Crystal molecular structure of 1,1′-μ-(CH2NH(O)C-1,2-C2B10H11)2 was determined by single crystal X-ray diffraction. Treatment of bis(carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 with ammonium or cesium fluoride results in partial deboronation of the ortho-carborane cages to the nido-carborane ones with formation of [7,7′(8′)-μ-(CH2NH(O)C(CH2)n-7,8-C2B9H11)2]2−. The attempted reaction of [7,7′(8′)-μ-(CH2NH(O)CCH2-7,8-C2B9H11)2]2− with GdCl3 in 1,2-dimethoxy- ethane did not give the expected metallacarborane. The stability of different conformations of Gd-containing metallacarboranes has been estimated by quantum-chemical calculations using [3,3-μ-DME-3,3′-Gd(1,2-C2B9H11)2]− as a model. It was found that in the most stable conformation the CH groups of the dicarbollide ligands are in anti,anti-orientation with respect to the DME ligand, while any rotation of the dicarbollide ligand reduces the stability of the system. This makes it possible to rationalize the design of carborane ligands for the synthesis of gadolinium metallacarboranes on their base.

Boron Neutron Capture Therapy (BNCT) is a binary therapy that promises to be suitable in treating many non-curable cancers. To that, the discovery of new boron compounds able to accumulate selectively in the tumour tissue is still required. Hypoxia, a deficiency of oxygen in tumor tissue, is a great challenge in the conventional treatment of cancer, because hypoxic areas are resistant to conventional anticancer treatments. 2-Nitroimidazole derivatives are known to be hypoxia markers due to their enrichment by bioreduction in hypoxic cells. In the present work, 2-nitroimidazole was chosen as the starting point for the synthesis of a new boron-containing compound based on a 1,3,5-triazine skeleton. Two o-carborane moieties were inserted to achieve a high ratio of boron on the molecular weight, exploiting a short PEG spacer to enhance the polarity of the compound and outdistance the active part from the core. The compound showed no toxicity on normal human primary fibroblasts, while it showed noteworthy toxicity in multiple myeloma cells together with a consistent intracellular boron accumulation.

The effect of substituting o‐carborane into the most sterically hindered positions of phenanthrene and benzo(k)tetraphene is reported. Synthesised via a Bull–Hutchings–Quayle benzannulation, the crystal structures of these non‐linear acenes exhibited the highest aromatic deformation parameters observed for any reported carborane compound to date, and among the largest carboranyl C−C bond length of all organo‐substituted o‐carboranes. Photoluminescence studies of these compounds demonstrated efficient intramolecular charge‐transfer, leading to aggregation induced emission properties. Additionally, an unusual low‐energy excimer was observed for the phenanthryl compound. These are two new members of the family of carborane‐functionalised non‐linear acenes, notable for their peculiar structures and multi‐luminescent properties., o ‐Carborane‐functionalised phenanthrene and benzo(k)tetraphene are reported in this work; two highly sterically hindered structures, with the latter displaying the largest aromatic deformation parameters of any organo‐substituted o‐carborane compound, and amongst the longest carboranyl C−C bond. Functionalisation of these polycyclic aromatic hydrocarbons induces stimuli‐responsive luminescence properties, including aggregation‐induced emission.

A set of mesomorphic materials in which the o-carborane cluster is covalently bonded to a cholesteryl benzoate moiety (mesogen group) through a suitably designed linker is described. The olefin cross-metathesis between appropriately functionalized styrenyl-o-carborane derivatives and a terminal alkenyl cholesteryl benzoate mesogen (all type I terminal olefins) leads to the desired trans-regioisomer, which is the best-suited configuration to obtain mesomorphic properties in the final materials. The introduction of different substituents (R = H (M2), Me (M3), or Ph (M4)) to one of the carbon atoms of the o-carborane cluster (Ccluster) enables the tailoring of liquid crystalline properties. Compounds M2 and M3 show the chiral nematic (N*) phase, whereas M4 do not show liquid crystal behavior. Weaker intermolecular interactions in the solid M3 with respect to those in M2 may allow the liquid crystallinity in M3 to be expressed as enantiotropic behavior, whereas breaking the stronger intermolecular interaction in the solid state of M2 leads directly to the isotropic state, resulting in monotropic behavior. Remarkably, M3 also displays the blue phase, which was observed neither in the chiral nematic precursor nor in the styrenyl-cholesterol model (M5) without an o-carborane cluster, which suggests that the presence of the cluster plays a role in stabilizing this highly twisted chiral phase. In the carborane-containing mesogens (M2 and M3), the o-carborane cluster can be incorporated without destroying the helical organization of the mesophase., This research was funded by MICINN grants (PID2019-106832RB-100 and CEX2019-000917-S) and Generalitat de Catalunya (2017/SGR/1720).

The new synthesized PdII complex cis-[(bipy)Pd(CBT)2] (bipy = 2,2'-bipyridyl; CBT = m-carborane-1-thiolate anion), which is a potential BNCT (boron neutron capture therapy) agent and of structure elucidated by single-crystal X-ray work, has been studied by infrared (IR) and ultraviolet-visible light (UV-vis) spectra and its properties compared with those of the previously reported and also the structurally characterized analogue trans-[(py)2Pd(CBT)2]. This trans species, prepared via a direct method, was previously isolated from a pyridine solution, consequent to the occurring releasing of the external Pd(CBT)2 moieties of the porphyrazine macrocycle [{Pd(CBT)2}4LZn]·xH2O (L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato anion), which is an active photosensitizer in photodynamic therapy (PDT) and a potential bimodal PDT/BNCT agent. The UV-vis spectral behavior of both cis and trans species in CHCl3 solution and in the gas phase has been examined in detail by density functional theory (DFT) and time-dependent density functional theory (TDDFT) studies devoted to explain their distinct behavior observed in the region of 400-500 nm, as determined by the presence in the cis structure of a vicinal arrangement of the two CBT groups, an ensemble of results closely similar to those observed for the macrocycles [{Pd(CBT)2}4LM]·xH2O (M = MgII(H2O), ZnII, PdII). It has also been experimentally proved the tendency of the cis isomer in CHCl3/pyridine solution to be changed to the respective trans analogue, with conversion occurring in two steps, as interpreted by detailed DFT studies.

The aryltellurenyl cation [2‐(tBuNCH)C6H4Te]+, a Lewis super acid, and the weakly coordinating carborane anion [CB11H12]−, an extremely weak Brønsted acid (pK a=131.0 in MeCN), form an isolable ion pair complex [2‐(tBuNCH)C6H4Te][CB11H12], in which the Brønsted acidity (pK a 7.4 in MeCN) of the formally hydridic B−H bonds is dramatically increased by more than 120 orders of magnitude. The electrophilic activation of B−H bonds in the carborane moiety gives rise to a proton transfer from boron to nitrogen at slightly elevated temperatures, as rationalized by the isolation of a mixture of the zwitterionic isomers 12‐ and 7‐[2‐(tBuN{H}CH)C6H4Te(CB11H11)] in ratios ranging from 62 : 38 to 80 : 20., B−H bond activation: The Lewis superacidic aryltellurenyl cation [2‐(tBuNCH)C6H4Te]+ increases the Brønsted acidity of the weakly coordinating carborane anion (CB11H12)− by more than 120 orders of magnitude. Upon heating, the formal B−H bond is converted into an acidic N−H bond, while a Te−B bond is formed. A mechanism for the electrophilic substitution is proposed.

This study aims at merging the therapeutic effects associated to the inhibition of Carbonic Anhydrase IX (CAIX), an essential enzyme overexpressed by cancer cells including mesothelioma and breast cancer, with those ones brought by the application of Boron Neutron Capture Therapy (BNCT). This task was pursued by designing a sulfonamido-functionalised-carborane (CA-SF) that acts simultaneously as CAIX inhibitor and boron delivery agent. The CAIX expression, measured by Western blot analysis, resulted high in both mesothelioma and breast tumours. This finding was exploited for the delivery of a therapeutic dose of boron (> 20 μg/g) to the cancer cells. The synergic cytotoxic effects operated by the enzymatic inhibition and neutron irradiation was evaluated in vitro on ZL34, AB22 and MCF7 cancer cells. Next, an in vivo model was prepared by subcutaneous injection of AB22 cells in Balb/c mice and CA-SF was administered as inclusion complex with a β-cyclodextrin oligomer. After irradiation with thermal neutrons tumour growth was evaluated for 25 days by MRI. The obtained results appear very promising as the tumour growth was definitively markedly lower in comparison to controls and the CAIX inhibitor alone. This approach appears promising and it call consideration for the design of new therapeutic routes to cure patients affected by this disease.

Boronated molecular systems can be applied to boron neutron capture therapy (BNCT). Among these systems, carborane-containing phthalocyanines (Pcs) are the most promising BNCT agents. Herein we report the new zinc (II) complex of the hexacationic Pc 6, which has been obtained as iodide salt through quaternization of the neutral precursor with methyl iodide. Compound 6 was synthesized over a sequence of four steps. The complex, and its precursors as well, were characterized by a combination of spectroscopic techniques, and their structures assessed by 1 H, 13 C, 11 B, and two-dimensional NMR spectroscopy experiments. Together with a marked tendency to aggregate, 6 showed appreciable solubility in water. Singlet oxygen quantum yield (ΦΔ ) of 0.38, and fluorescence quantum yield (ΦF ) of 0.13 were obtained for 6 in a DMF solution. The complex proved to be very effective in enriching UMR-106 cells with 10 B, showing very good performance even in case of very low concentrations exposure, i. e. 1 ppm, that moreover resulted in a mild cytotoxic effect. Such a feature can be related to the polycationic nature of the complex, and hence to the well-known propensity of positively charged species to enter the cellular membrane or to adhere to its external surface.

5-Lipoxygenase converts arachidonic acid into leukotrienes, which are involved in inflammation and angiogenesis. The introduction of carboranes can improve the pharmacokinetic behavior of metabolically less stable pharmaceutics. Herein we report the syntheses of several carborane-based inhibitors of the 5-lipoxygenase pathway. The isosteric replacement of phenyl rings by carboranes leads to improved cytotoxicity toward several melanoma and colon cancer cell lines. For the colon cancer cell line HCT116, the co-inhibition of heat shock protein 90 was observed.

The direct C–H functionalization methodology has first been applied to perform transition metal-free C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyllithium. This atom- and step-economical approach, based on one-pot reactions of nucleophilic substitution of hydrogen (SNH) in non-aromatic azaheterocycles, affords novel imidazolyl-modified carboranes of two types (N-oxides and their deoxygenative analogues), which are particularly of interest in the design of advanced materials.

A small library of carborane-BODIPY/aza-BODIPY dyads were efficiently synthesized by means of a novel convergent synthetic approach, the key step of which is a Pd-catalyzed Heck coupling reaction. The structural characterization and photoluminescence properties of the newly synthesized dyads were evaluated. The presence of the carborane did not significantly alter the photophysical patterns of the BODIPY or aza-BODIPY in the final fluorophores, but it produced a decrease of the emission fluorescent quantum yields that was in the range from 1.4 % for aza-BODIPY to 48 % for BODIPY-dyads. The carborane-BODIPY dyads were successfully incorporated into cells, especially compounds 2, 4 and 13, demonstrating their cytoplasmic localization. The fluorescent and biocompatibility properties make these compounds good candidates for in vitro cell tracking.

The synthesis of a highly twisted chrysene derivative incorporating two electron deficient o‐carboranyl groups is reported. The molecule exhibits a complex, excitation‐dependent photoluminescence, including aggregation‐induced emission (AIE) with good quantum efficiency and an exceptionally long singlet excited state lifetime. Through a combination of detailed optical studies and theoretical calculations, the excited state species are identified, including an unusual excimer induced by the presence of o‐carborane. This is the first time that o‐carborane has been shown to induce excimer formation ab initio, as well as the first observation of excimer emission by a chrysene‐based small molecule in solution. Bis‐o‐carboranyl chrysene is thus an initial member of a new family of o‐carboranyl phenacenes exhibiting a novel architecture for highly‐efficient multi‐luminescent fluorophores.

The methyl sulfide derivatives of cobalt bis(dicarbollide) [8,8'-(MeS)2-3,3'-Co(1,2-C2B9H10)2]-, [4,4'-(MeS)2-3,3'-Co(1,2-C2B9H10)2]- and [4,7'-(MeS)2-3,3'-Co(1,2-C2B9H10)2]- were synthesized by the reaction of CoCl2 with [10-MeS-7,8-C2B9H11]- and [9-MeS-7,8-C2B9H11]-, respectively, in strong alkaline aqueous media. The 4,4'-(rac)- and 4,7'-(meso)-isomers were separated by column chromatography on silica as the tetrabutylammonium salts. The structures of (Bu4N)[8,8'-(MeS)2-3,3'-Co(1,2-C2B9H10)2], (Bu4N)[4,4'-(MeS)2-3,3'-Co(1,2-C2B9H10)2] and (Bu4N)[4,7'-(MeS)2-3,3'-Co(1,2-C2B9H10)2] were determined by single crystal X-ray diffraction. In the solid state, the rotation of the two dicarbollide ligands with respect to each other is hampered due to formation of intramolecular CHcarb ***S(Me) hydrogen bonds between the ligands, that results in stabilization of definite rotamers - transoid- in the case of 8,8'-isomer, and gauche- in the case of 4,4'- and 4,7'-isomers. These data are in a good agreement with results of the quantum chemical calculations.

The synthesis of two biscarboranyl (bc) magnesium reagents is described. Treatment of 1,1'-bis(o-carborane) (H2-bc) or 8,8',9,9',10,10',12,12'-octamethyl-1,1'-bis(o-carborane) (H2-Mebc) with Mg(n-Bu)2 in 1,2-dimethoxyethane (DME) affords (bc)Mg(DME)2 (1a-b) as crystalline solids. The magnesium compounds, which have been characterized by NMR spectroscopy and single crystal X-ray crystallography in the case of 1a, serve as competent Grignard-type reagents to generate bc-containing species of tin from Me2SnCl2 (2a-b). The type of substitution of the bis(o-carboranyl) ligand framework is found to strongly effect the electronic character of the tin center, as judged by 119Sn NMR spectroscopy. The disclosed compounds, which are stable solids under an atmosphere of dry nitrogen gas at room temperature, provide a new class of bc-transfer reagents.

Metallacarboranes with the shape of the Greek letter θ, such as [Co(C2B9H11)2]−, were tested, for the first time, as efficient photoredox catalysts in the oxidation of aromatic and aliphatic alcohols in water. Their efficiency is linked to their high solubility in water, their high oxidizing power (Co4+/3+), and their absence of fluorescence on excitation, among others. In most of the studied examples, using a catalyst load of 0.4 mol % gave high yields of 90–95 % with selectivity greater than 99 %. By reducing the catalyst load to 0.01 mol %, quantitative conversion of reactants to products was achieved, in some cases with greater than 99 % yield, high catalyst efficiency reaching a turnover number of 10 000, and a higher yield with a 45 times lower concentration of catalyst. The metallacarboranes can be recovered easily by precipitation on addition of [NMe4]Cl. A pathway for the photoredox‐catalyzed oxidation of alcohols is proposed., This research has been financed by MINECO (CTQ2016‐75150‐R and CTQ2015‐66143‐P) and Generalitat de Catalunya (2017 SGR 1720). “Severo Ochoa” Program for Centers of Excellence in R&D 234 (SEV‐2015‐0496) is appreciated. We gladly thank the CESCA, the Supercomputing Center of Catalonia, for providing us with access to their computers. Z.K. is grateful for the general support of the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie grant agreement MSCA‐IF‐2016‐751587.

About 95 % of people diagnosed with glioblastoma die within five years. Glioblastoma is the most aggressive central nervous system tumour. It is necessary to make progress in the glioblastoma treatment so that advanced chemotherapy drugs or radiation therapy or, ideally, two‐in‐one hybrid systems should be implemented. Tyrosine kinase receptors–inhibitors and boron neutron capture therapy (BNCT), together, could provide a therapeutic strategy. In this work, sunitinib decorated‐carborane hybrids were prepared and biologically evaluated identifying excellent antitumoral‐ and BNCT‐agents. One of the selected hybrids was studied against glioma‐cells and found to be 4 times more cytotoxic than sunitinib and 1.7 times more effective than 10B‐boronophenylalanine fructose complex when the cells were irradiated with neutrons., This work was supported in part by grant by FCE‐ANII (FCE_3_2018_1_148288). M.C., P.C., and H.C. are Sistema Nacional de Investigadores‐Agencia Nacional de Investigación e Innovación (ANII) researchers. M.C. thanks CSIC‐Universidad de la República (UdelaR) (Grupo I+D, CSIC‐421) for his scholarships. M.C. thanks funding from ANII for his doctoral‐scholarship (POS_NAC_2015_1_110068).

We have examined the insertion of carbenes carrying leaving groups into the [nido-B11H13]2&minus, dianion to form the [closo-1-CB11H12]&minus, anion. The best procedure uses CF3SiMe3 and LiCl as the source of CF2. It is simple, convenient and scalable and proceeds with 70&ndash, 90% yield. Density functional calculations have been used to develop a mechanistic proposal that accounts for the different behavior of CF2, requiring only one equivalent of base for successful conversion of Na[nido-B11H14]&minus, to [closo-1-CB11H12]&minus, and CCl2 and CBr2, which require more.

Off-cycle processes in catalytic reactions can dramatically influence the outcome of the chemical transformation and affect its yield, selectivity, rate, and product distribution. While the generation of off-cycle intermediates can complicate reaction coordinate analyses or hamper catalytic efficiency, the generation of such species may also open new routes to unique chemical products. Recently, we reported the Pd-mediated functionalization of carboranes with a range of O-, N-, and C-based nucleophiles. By utilizing a Pd-based catalytic system supported by a biaryl phosphine ligand developed by Buchwald and co-workers, we discovered an off-cycle isomerization process (“cage-walking”) that generates four regioisomeric products from a single halogenated boron cluster isomer. Here we describe how several off-cycle processes affect the regioisomer yield and distribution during Pd-catalyzed tandem cage-walking/cross-coupling. In particular, tuning the transmetallation step in the catalytic cycle allowed us to incorporate the cage-walking process into Pd-catalyzed cross-coupling of sterically unencumbered substrates, including cyanide. This work demonstrates the feasibility of using tandem cage-walking/cross-coupling as a unique low-temperature method for producing regioisomers of mono-substituted carboranes.

Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic drug target for the treatment of cancer. Carboranes, an icosahedral arrangement of eleven boron atoms plus one carbon atom with unique pharmacological properties such low toxicity, isosterism with phenyl ring and stability to hydrolysis. On the other hand, carboranes are known to increase the interaction of ligand with non-polar region of the protein provides an excellent platform to explore these carboranes towards designing and development of novel, potent and target specific drug candidates with further enhanced binding affinities. Despite of their many potential applications, molecular modeling studies of carborane-substituted ligands with macromolecules have been rarely reported. Previously, we have demonstrated the promising high binding affinity of Withaferin-A (WA) for IDO. In this present study, we investigated the effect of carborane substitutions on WA compound towards developing novel analogs for target specific IDO inhibition with better potency. Interesting docked poses and molecular interactions for the carborane substituted WA ligands were elucidated. Based on our In-silico studies, carborane substituted at various position of WA has shown enhanced binding affinity towards IDO, worth of considering for further studies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common way of treating inflammatory disorders. Their widespread use helped reveal their other modes of action as pharmaceuticals, such as a profound effect on various cancers. Celecoxib has proven to be a very prominent member of this group with cytostatic activities. On the other hand, the highly dynamic field of drug design is constantly searching for new ways of modifying known structures to obtain more powerful and less harmful drugs. A very interesting development is the implementation of carboranes in pharmacologically active structures, mostly as phenyl mimetics. Herein we report the synthesis of three carborane-containing derivatives of the COX-2-selective NSAID celecoxib. The new compounds proved to have promising cytostatic potential against various melanoma and colorectal adenocarcinoma cell lines. Inhibited proliferation accompanied by caspase-independent apoptotic cell death was found to be the main cause of decreased cell viability upon treatment with the most efficient celecoxib analogue, 3 b (4-[5-(1,7-dicarba-closo-dodecaboranyl)-3-trifluoromethyl-1H-pyrazol-1-yl]-1-methylsulfonylbenzene).

Boron has been employed in materials science as a marker for imaging specific structures by electron energy loss spectroscopy (EELS) or secondary ion mass spectrometry (SIMS). It has a strong potential in biological analyses as well; however, the specific coupling of a sufficient number of boron atoms to a biological structure has proven challenging. Herein, we synthesize tags containing closo-1,2-dicarbadodecaborane, coupled to soluble peptides, which were integrated in specific proteins by click chemistry in mammalian cells and were also coupled to nanobodies for use in immunocytochemistry experiments. The tags were fully functional in biological samples, as demonstrated by nanoSIMS imaging of cell cultures. The boron signal revealed the protein of interest, while other SIMS channels were used for imaging different positive ions, such as the cellular metal ions. This allows, for the first time, the simultaneous imaging of such ions with a protein of interest and will enable new biological applications in the SIMS field. peerReviewed

This work encompasses a comprehensive study of host···guest interactions between cyclic trimer metal‐carborane [Au3(1,2‐C2B10H10)3]3−, and several guest species as cations (H+, Li+, Be2+, Hg2+), anions (F−, H−, Cl−, Br−, I−, HCC−), and neutral molecules (H2, CO2, I2, HCCH, N2). A computational study has been carried out in order to evaluate energetic profiles and determine the contribution for attractive or repulsive interactions between guest and host. Several cases call our attention as a function of the energy minima. For instance, all above cations form stable minima as guest complexes with the three gold atoms of the host. Unexpectedly, pyramidal H− or F− species are obtained as energy minima, while other anions give completely repulsive interactions. Finally, the CO2 molecule is also trapped inside the trinuclear ring., J. M. O-E. is grateful to the program “Salvador de Madariaga” of the Spanish Ministerio de Educación, Cultura y Deporte (PRX17/00488). Financial support was provided by the Spanish Ministerio de Economía y Competitividad (CTQ2015-64579-C3-1-P).