Search

Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.

A simple synthetic way to obtain a decachloro derivative of cobalt bis(dicarbollide) has been found. The reaction of cesium salt of cobalt bis(dicarbollide) anion with aluminum chloride in chloroform under reflux conditions results in Cs[3,3′-Co(4,7,8,9,12-Cl5-1,2-C2B9H6)2] of high purity and good yield.

Herein, we report the unique solid-state excimer emission of three types of acridine-tethered o-carboranes with variable degrees of methylation at the o-carborane unit. They all showed columnar packing structures based on dimer formation, and two types of π-overlapping motifs were alternately stacked. From the photoluminescence (PL) measurements on the crystalline samples, it was found that three types of luminescence bands can simultaneously appear: monomer emission, excimer emission from the moderately π-stacked intra-dimer unit, and excimer emission from the widely π-stacked inter-dimer unit. Consequently, the PL colors were drastically changed by the steric effect of the methyl groups, with a strong correlation found between the π-overlapping and excimer character. In addition, variable-temperature PL measurements revealed that these PL species should be in thermal equilibrium at room temperature, with the intensity ratios sensitive toward temperature changes.

The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. We, therefore, focus on the incorporation of metabolically stable, sterically demanding and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, we present the first carborane-containing dual COX-2/5-LO inhibitors derived from RWJ-63556. The replacement of the fluorophenyl moiety by meta- or para-carborane resulted in five carborane-containing derivatives 3, 6, 9, 13 and 17 that show high inhibitory activities toward COX-2 and 5-LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta-carborane derivative 3 shows higher anticancer activity compared to RWJ-63556 based on accumulation of lipid droplets in the cells due to blockage of the COX-2 and 5-LO pathways, indicating a promising approach for the design of potent dual COX-2/5-LO inhibitors.

Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that show no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibit lower anticancer activity compared to the related di-tert-butylphenols. Inter-estingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell pro-liferation more potently than its carbon-based R-830 counterpart. Considering all the ad-vantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.

We report that the carborane-based metal-organic framework (MOF) mCB-MOF-1 can achieve high adsorptive selectivity for CO2:N2 mixtures. This hydrophobic MOF presenting open metal sites shows high CO2 adsorption capacity and remarkable selectivity values that are maintained even under extremely humid conditions. The comparison of mCB-MOF-1' with MOF-74(Ni) demonstrates the superior performance of the former under challenging moisture operation conditions., The work has been supported by the European Union (ERC-2016-CoG 724681-S-CAGE), MINECO PID2019-106832RB-100, and PID2020-117177GB-I00 grants, CEX2019-000919-M, funded by MCIN/AEI/10.13039/501100011033, the Generalitat Valenciana (PROMETEO program), and the Generalitat de Catalunya (2017/SGR/1720). L.G. acknowledges the China Scholarship Council (CSC) for his Ph.D. grant (201808310071). E.A.-G thanks MICINN for a Juan de la Cierva Formación fellowship (FJC2019-039015-I) and for a Margarita Salas Requalification Programme (MS21-035). This study forms part of the Advanced Materials program and was supported by MCIN with funding from European Union NextGenerationEU (PRTR-C17.I1) and by Generalitat Valenciana (project MAF/2022/31)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

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)

The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new closo- and nido-carborane-containing folic acid bis-amides containing 18–20 boron atoms per molecule. Folic acid derivatives containing nido-carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.0 µg B/106 cells in the case of U87 MG human glioblastoma cells). The results obtained demonstrate the high potential of folic acid–nido-carborane conjugates as boron delivery agents to tumour cells for application in BNCT.

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.

It is still challenging to realize a dual-emission system, in which two luminescent bands simultaneously appear by photoexcitation, in solid with organic dyes due to the difficulty in regulation of electronic properties in the excited state and concentration quenching. o-Carborane is known to be a versatile platform for constructing solid-state emitters since the sphere boron cluster is favorable for suppressing intermolecular interactions and subsequently concentration quenching. Here, we show solid-state dual-emissive o-carborane derivatives. We prepared 4 types of o-carborane derivatives and found dual-emission behaviors both in solution and solid states. By regulating the rotation at the o-carborane unit with the intramolecular C[cage]H⋅⋅⋅O interaction, the dual-emission intensity ratios were changed. Finally, it was demonstrated that the overall photoluminescence spectra can be estimated using the binding energy of intramolecular interactions.

A large number of 2D/2D and 3D/3D aromatic fusions that keep their aromaticity in the fused compounds have been synthesized. In addition, we have previously proven the electronic relationship between the 3D aromaticity of boron hydrides and the 2D aromaticity of PAHs. Here we report the possible existence of 3D/2D aromatic fusions that retain the whole aromaticity of the two units. Our conclusion is that such a 3D/2D aromatic combination is not possible due to the ineffective overlap between the π-MOs of the planar species and the n + 1 molecular orbitals in the aromatic cage that deter an effective electronic delocalization between the two fused units. We have also proven the necessary conditions for 3D/3D fusions to take place, and how aromaticity of each unit is decreased in 2D/2D and 3D/3D fusions., This work has been supported by the Ministerio de Ciencia e Innovación of Spain (Projects PID2020-113711GB-I00 (M.S.), PID2019-106830GB-I00 (J.P.), PID2019-106832RB-100 (C.V. and F.T.) and MDM-2017-0767 (J.P.)) and the Generalitat de Catalunya (projects 2017SGR39 (M.S.), 2017SGR1720 (C.V. and F.T.) and 2017SGR348 (J.P.)). Excellent service by the Supercomputer center of the Consorci de Serveis Universitaris de Catalunya (CSUC) is gratefully acknowledged., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Ferrocene and its derivatives have been extensively used as an internal reference in electrochemical processes. Yet, they possess limitations such as solvent restrictions that require chemical modifications. In this regard, we have studied the use of metallacarboranes [3,3'-M(1,2-C2B9H11)2]- (M = Co, Fe) as general internal reference systems and have proven their suitability by thoroughly investigating their electrochemical properties in both aqueous and organic electrolytes without any derivatization., This work was funded by the Spanish Ministry of Science, through the ‘‘Severo Ochoa’’ Programme for Centres of Excellence in R&D (CEX2019-000917-S) as well as the Ministerio de Economia y Competitividad (PID2019-106832RB-I00), (PID2020- 116728RB-I00, CTQ2015-71955-RED ELECTROBIONET) and Generalitat de Catalunya (2017SGR1720) are appreciated. J. A. M. Xavier acknowledges DOC-FAM programme under the Marie Sklodowska-Curie grant agreement no. 754397 and is enrolled in the PhD programme in UAB. Support from the Community of Madrid (TRANSNANOAVANSENS S2018/NMT-4349), is acknowledged., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Modern computational protocols based on the density functional theory (DFT) infer that polyhedral closo ten-vertex carboranes are key starting stationary states in obtaining ten-vertex cationic carboranes. The rearrangement of the bicapped square polyhedra into decaborane-like shapes with open hexagons in boat conformations is caused by attacks of N-heterocyclic carbenes (NHCs) on the closo motifs. Single-point computations on the stationary points found during computational examinations of the reaction pathways have clearly shown that taking the “experimental” NHCs into account requires the use of dispersion correction. Further examination has revealed that for the purposes of the description of reaction pathways in their entirety, i.e., together with all transition states and intermediates, a simplified model of NHCs is sufficient. Many of such transition states resemble in their shapes those that dictate Z-rearrangement among various isomers of closo ten-vertex carboranes. Computational results are in very good agreement with the experimental findings obtained earlier.

Polyhedral boron clusters and their applications have been subject to research in many fields such as medicine, materials science, catalytic applications, energy studies, etc. These molecules owe their popularity to their exceptional 3D stable structures, as well as their various sought-after properties in many applications. This doctoral thesis was prepared within the focus of a computational investigation of different polyhedral borane and carborane clusters by using DFT methods. The results of our studies were reported in two main chapters (Chapters 3 and 4). In the first part (Chapter 3), theoretical evaluation of relative stabilities and electronic structure for [BnXn] 2− clusters were provided. The structural and electronic characteristics of [BnXn] 2− clusters were examined by comparison with the [B12X12] 2− counterparts with a focus on the substituent effects (X = H, F, Cl, Br, CN, BO, OH, NH2). The effects of the substituents were discussed in relation to their mesomeric (±M) and inductive (±I) effects. The results showed that the icosahedral barrier can be reduced through substitution by destabilizing the [B12X12] 2− cluster with symmetry-reducing ligands or ligands with +M effects rather than stabilizing the larger clusters. In the second part (Chapter 4), the investigation of the photophysical properties of carborane-containing luminescent systems was presented. The o-CB-Anth system is known to exhibit a dual-emission property by radiating in the visible region from two low energy conformations with local excited (LE) and hybridized local and charge transfer (HLCT) characters, however, it shows a very low emission quantum yield in solution state similar to many other CB-luminescent systems. In this section, the excited-state potential energy surface (PES) of o-CB-Anth and o-CB-Pent were investigated in detail and the effect of a low-lying CT on the low quantum yield was discussed. Çokyüzlü bor kümeleri ve uygulamaları tıp, malzeme bilimi, katalitik uygulamalar, enerji çalışmaları vb. Birçok alanda araştıma konusu olmuştur. Bu moleküller, popülerliklerini kararlı 3 boyutlu yapılarının yanında sahip oldukları, ve birçok uyglama alanında aranan özelliklerine borçludur. Bu doktora tezi, farklı çokyüzlü boran ve karboran kümelerinin yoğunluk fonksiyonu theorisi metotları kullanılarak hesaplamalı olarak incelenmesi odağında hazırlanmıştır. Çalışmalarımızın sonuçları iki ana bölümde rapor edilmiştir (Chapter 3 ve 4). Birinci bölümde, [BnXn] 2− kümelerinin bağıl kararlılıklarının ve elektronik yapılarının teorik bir değerlendirmesi verilmektedir. [BnXn] 2− kümelerinin yapısal ve elektronik karakterleri, [B12X12] 2− molekülleri ile karşılaştırılarak, sübstitüent etkileri (X = H, F, Cl, Br, CN, BO, OH, NH2) incelendi. Bu etkiler, substitüentlerin mezomerik (±M) ve endüktif (±I) etkileriyle ilişkilendirilerek tartışıldı. Sonuçlar, ikosahedral bariyerin, daha büyük kümeleri stabilize etmek yerine simetriyi azaltan ligandlar veya +M etkileri olan ligandlarla [B12X12] 2− kümesini kararsızlaştırarak azaltılabileceğini göstermektedir. İkinci bölüm, karboran kümeleri ve bunların ışık yayan sistemler üzerindeki etkileri çerçevesinde yaptığımız çalışmayı kapsamaktadır. o-CB-antrasin sisteminin, yerel uyarılmış (LE) ve hibritleştirilmiş yerel ve yük transferi (HLCT) karakterlerine sahip iki düşük enerjili konformasyondan görünür bölgede ışıma yaparak çift emisyon özelliği gösterdiği bilinmektedir, ancak diğer birçok CB bazlı ışık yayan sistemde de görüldüğü gibi çözücü içerisinde çok düşük emisyon kuantum verimine sahiptir. Bu bölümde, o-CB-Anth ve o-CB-Pent sistemlerinin uyarılmış durum potansiyel enerji yüzeyi (PES) detaylı olarak incelenmiş ve düşük seviyeli bir yük transfer (CT) durumunun kuantum verimi üzerindeki etkisi tartışılmıştır.

Luminescent lanthanide metal-organic frameworks (Ln-MOFs) have been shown to exhibit relevant optical properties of interest for practical applications, though their implementation still remains a challenge. To be suitable for practical applications, Ln-MOFs must be not only water stable but also printable, easy to prepare, and produced in high yields. Herein, we design and synthesize a series of m CB-Eu y Tb 1-y (y = 0-1) MOFs using a highly hydrophobic ligand mCBL1: 1,7-di(4-carboxyphenyl)-1,7-dicarba-closo-dodecaborane. The new materials are stable in water and at high temperature. Tunable emission from green to red, energy transfer (ET) from Tb3+ to Eu3+, and time-dependent emission of the series of mixed-metal m CB-Eu y Tb 1-y MOFs are reported. An outstanding increase in the quantum yield (QY) of 239% of mCB-Eu (20.5%) in the mixed mCB-Eu0.1Tb0.9 (69.2%) is achieved, along with an increased and tunable lifetime luminescence (from about 0.5 to 10 000 μs), all of these promoted by a highly effective ET process. The observed time-dependent emission (and color), in addition to the high QY, provides a simple method for designing high-security anticounterfeiting materials. We report a convenient method to prepare mixed-metal Eu/Tb coordination polymers (CPs) that are printable from water inks for potential applications, among which anticounterfeiting and bar-coding have been selected as a proof-of-concept., This work was financially supported by the MINECO (PID2019-106832RB-I00), MICINN through the Severo Ochoa Program for Centers of Excellence for the FUNFUTURE (CEX2019-000917-S, MDM-2017-0767, and SEV-2017-0706 projects), grant RTI2018-098027-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe and the Generalitat de Catalunya (2017/SGR/1720 and SGR2017-1289). Z.L. is enrolled in the UAB Ph.D. program and acknowledges the China Scholarship Council (CSC) for his Ph.D. grant (201808310071)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

In this study of GdxFe3-xO4 compound core silane shell nanoparticles method is represented. Samples were analyzed with SEM, EDA and FTIR spectroscopy. Further attaching of carborane compounds is discussed. Products can be used in biomedical applications for MRI imaging and drug delivery for NCT, so can be considered as potential theranostic agents for cancer treatment. © 2022 Institute of Physics Publishing. All rights reserved. This study was funded by the Ministry of Education and Science of the Republic of Kazakhstan (grant No AP08051954).

This dissertation is dedicated to the development of donor-stabilized silylium ions and their application in catalytic organic transformations. The first part of this dissertation focuses on the synthesis and characterization of different donor-stabilized bis(silylium) ions. The silylium salts were synthesized by the Corey hydride transfer procedure using trityl cation with weakly coordinating counteranions. The formation of bis(silylium) ions by two-fold hydride abstraction from bis(hydrosilanes) was dependent on the structure of the precursor backbone. The primary reaction outcome was the formation of bissilylhydronium ions with varying stability based on the nature of the flexible and rigid linker, respectively. At this stage, it was possible to obtain the first molecular structure of a bissilylhydronium ion with unsymmetric silyl substitution. The formation of the 3-center-2-electron (3c2e) SiHSi bond was overcome by manipulating the distance between the two Lewis acidic sites. We eventually succeeded in isolating three bis(silylium) ions in form of their carborate salts, one of which was characterized by X-ray diffraction analysis. DFT calculations shed light on the viability of two-fold hydride abstraction from precursors with a flexible linker. In a follow-up project, we investigated the formation of frustrated Lewis pairs (FLPs) or frustrated radical pairs (FRPs) by the reaction of a bis(silylium) ion with several bulky phosphanes. In the case of FRP formation, we envisaged to indirectly detect the previously undetected silyl radical in the form of the respective disilane. However, this attempt was unsuccessful. The second part of this dissertation deals with silylium-ion-promoted catalytic transformations. The high reactivity of silylium ions was demonstrated in the ring-opening hydrosilylation of unactivated cyclopropanes. DFT calculations revealed an activation mode of the cyclopropane ring in which the proximal bond is polarized by a silylium ion, resulting in ring-opening facilitated by the γ-silicon effect. The formed carbenium ion underwent either a Wagner–Meerwein rearrangement or direct hydride transfer from a hydrosilane, leading to regioisomeric hydrosilylated products. In a follow-up project, a silylium-ion-mediated isomerization of unactivated cyclopropyl to the corresponding allyl groups was disclosed. Within this study, an unusual intramolecular arene-stabilized silylium ion was isolated and characterized. Moreover, this reactive intermediate was capable of cleaving the Si–Si bond in hexamethyldisilane. Based on this finding, a catalytic disilylation of both cyclopropanes and α-olefins was realized. Next, we established a method for the silicon electrophile-mediated hydrosilylation of ketenes to arrive at synthetically useful aldehyde-derived β,β-di- and β-monoaryl-substituted silyl enol ethers. The observed O-silylation of ketenes with silylium ions contradicted an earlier report on C-silylation of ketenes. Both silylium ion/hydrosilane and B(C6F5)3/hydrosilane combinations were surveyed for the catalytic hydrosilylation, with the latter proceeding with higher efficiency., Die vorliegende Dissertation widmet sich der Entwicklung donorstabilisierter Silyliumionen und ihrer Anwendung in katalytischen Prozessen. Der erste Teil dieser Dissertation konzentriert sich auf die Synthese und Charakterisierung verschiedener donorstabilisierter Bis(silylium)ionen. Die Silyliumionen wurden durch Corey-Hydridtransfer unter Verwendung des Tritylkations mit schwach koordinierenden Gegenanionen dargestellt. Die Bildung von Bis(silylium)ionen durch zweifache Hydridabstraktion von Bis(hydrosilanen) war abhängig von der Struktur der Vorläuferrückgrate. Der primär beobachtete Reaktionsausgang war die Bildung von Bissilylhydroniumionen mit unterschiedlicher Stabilität, je nach Art der flexiblen bzw. starren Verknüpfungseinheit. Zu diesem Zeitpunkt war es möglich, die erste Molekülstruktur eines Bissilylhydroniumions mit unsymmetrischer Silylsubstitution zu erhalten. Die Bildung der 3-Zentren-2-Elektronen (3c2e) SiHSi-Bindung wurde durch gezielte Veränderung des Abstandes der beiden Lewis-sauren Positionen überwunden. Letztlich gelang es, drei Bis(silylium)ionen in Form ihrer Carboratsalze zu isolieren, von denen eines röntgenographisch charakterisiert wurde. DFT-Berechnungen gaben Aufschluss über die Durchführbarkeit einer zweifachen Hydridabstraktion aus Vorläufern mit einem flexiblen Linker. In einem Folgeprojekt untersuchten wir die Bildung von frustrierten Lewis-Paaren (FLPs) oder frustrierten Radikalpaaren (FRPs) durch die Reaktion eines Bis(silylium)ions mit verschiedenen sperrigen Phosphanen. Im Falle der FRP-Bildung wollten wir indirekt das bisher nicht nachgewiesene Silylradikal in Form des entsprechenden Disilans nachweisen. Dieser Versuch war jedoch erfolglos. Der zweite Teil dieser Dissertation befasst sich mit silyliumionvermittelten katalytischen Umsetzungen. Die hohe Reaktivität von Silyliumionen wurde durch die ringöffnende Hydrosilylierung nichtaktivierter Cyclopropane demonstriert. DFT-Berechnungen ergaben einen Aktivierungsmodus des Cyclopropanrings, bei dem die proximale Bindung durch ein Silyliumion polarisiert wird, was zu einer durch den γ-Siliciumeffekt begünstigten Ringöffnung führte. Das gebildete Carbeniumion durchlief entweder eine Wagner–Meerwein-Umlagerung oder erfuhr eine direkte Hydridübertragung durch ein Hydrosilan, was zu regioisomeren hydrosilylierten Produkten führte. In einem Folgeprojekt wurde eine silyliumionvermittelte Isomerisierung von nichtaktivierten Cyclopropyl- zu den entsprechenden Allylgruppen offengelegt. Im Rahmen dieser Studie wurde ein ungewöhnliches intramolekulares arenstabilisiertes Silyliumion isoliert und charakterisiert. Außerdem war dieses reaktive Zwischenprodukt in der Lage, die Si–Si-Bindung in Hexamethyldisilan zu spalten. Basierend auf dieser Erkenntnis wurde eine katalytische Disilylierung sowohl von Cyclopropanen als auch von α-Olefinen realisiert. Als nächstes etablierten wir eine Methode für die siliciumelectrophilvermittelte Hydrosilylierung von Ketenen, um zu synthetisch nützlichen, von Aldehyden abgeleiteten β,β-di- und β-monoarylsubstituierten Silylenolethern zu gelangen. Die beobachtete O-Silylierung von Ketenen mit Silyliumionen widersprach einem früheren Bericht über die C-Silylierung von Ketenen. Für die katalytische Hydrosilylierung wurden sowohl Silyliumion/Hydrosilan- als auch B(C6F5)3/Hydrosilan-Kombinationen untersucht, wobei letztere mit höherer Effizienz abliefen.

This study shows tuning of sensitivity in thermochromic luminescence from triphenylamine‐substituted o‐carboranes by regulating rotation barriers with a substituent effect. A series of o‐carborane dyads with various numbers of methyl substituents were prepared, and their optical properties were compared. Initially, significant dual‐emission properties consistent of the locally excited (LE) state and the induced charge transfer (ICT) state were observed from the solid samples of all dyads. In particular, diverse responses were obtained by cooling from the dyads. The pristine and mono‐substituted dyads presented thermally independent emission during temperature changes, whereas the detected thermochromic luminescence with drastic color change from red to blue originated from the alteration of intensity ratios between LE and CT emission bands. From mechanistic studies (experimental and theoretical), it was clearly shown that the difference in the rotation barrier of the o‐carborane unit caused by the substituent effect should play a key role in variable sensitivity in luminescent chromic behaviors in temperature change.

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.

The time‐dependent emission enhancement (TDEE) phenomena of the 1‐(o‐carboran‐1‐yl)ethynylpyrene dyad were reported. It was found that the emission intensity from the dyad increased in tetrahydrofuran (THF), acetone and dichloromethane with increasing incubation time. From the mechanistic studies, it was suggested that agglomeration of the dyad gradually proceeded in these media, followed by expression of excimer luminescence. Additionally, it was shown that the rates of TDEE of the dyad were sensitively accelerated in the presence of a trace amount of water. Based on this fact, a detection system for water contents in acetone was constructed. Before and after incubation for 96 h at room temperature, time courses of changes in optical properties were monitored. Finally, water contents in acetone can be estimated by the degrees of TDEE and emission color changes in the range from 0.1 wt % to 2.0 wt % and from 2.0 wt % to 20 wt %, respectively.

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.

In a previous study we synthesized a series of bis‐o‐carborane‐modified acenes and revealed various unique luminescence properties, such as highly efficient solid‐state emission and luminochromism. Here we report further enhancement of the luminescence efficiencies of bis‐o‐carborane‐modified acenes by thermally induced structural rearrangement from ortho‐ to meta‐carborane. We found that the thermal rearrangement of the anthracene derivative 1 occurred close to the melting point and gave luminescent products. From a detailed investigation of the product obtained from 1, the transformation of the molecular structure was proven by X‐ray crystallography. In addition, the analytical data indicated that rearrangement caused by heating at 300 °C occurred at only one of the two o‐carborane units. In accord with the results of theoretical investigations of the transition states of 1 by quantum chemical calculations, we propose that the thermal rearrangement could proceed because of a low activation energy in the first rearrangement step due to the presence of the anthracene. On the basis of optical measurements, enhancements of not only luminescence efficiencies but also aggregation‐induced emission were observed. Furthermore, we have demonstrated that this strategy for enhancing emission properties is applicable ot the corresponding tetracene derivative, resulting in a deep‐red luminescent dye.

Keivan Sadrerafi, Emilia O Mason, Mark W Lee Jr Department of Chemistry, University of Missouri, Columbia, MO, USA Purpose: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl)-7-(4′-(trans-3″-(3‴-pyridyl)acrylamido)butyl)-1,7-dicarbadodecaborane (hm-MC4-PPEA), was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt). Nampt has been shown to be upregulated in most cancers and is a promising target for the treatment of many different types of cancers, including breast cancers. Patients and methods: To increase the selectivity of hm-MC4-PPEA toward cancer cells, three prodrugs were synthesized with different hydrolyzable linkers: ester, carbonate, and carbamate. Using click chemistry a fluorophore was attached to these prodrugs to act as a model for our conjugation strategy and to serve as an aid for prodrug stability studies. The stabilities of these drug conjugates were tested in phosphate-buffered saline (PBS) at normothermia (37°C) using three different pH levels, 5.5, 7.5, and 9.5, as well as in horse serum at physiological pH. The stability of each was monitored using reversed-phase HPLC equipped with both diode array and fluorescence detection. The inhibitory activity of hm-MC4-PPEA was also measured using a commercially available colorimetric assay. The biological activities of the drug conjugates as well as those of the free drug (hm-MC4-PPEA), were evaluated using the MTT assay against the human breast cancer cell lines T47D and MCF7, as well as the noncancerous, transformed, Nampt-dependent human breast epithelium cell line 184A1.Results: hm-MC4-PPEA showed to be a potent inhibitor of recombinant Nampt activity, exhibiting an IC50 concentration of 6.8 nM. The prodrugs showed great stability towards hydrolytic degradation under neutral, mildly acidic and mildly basic conditions. The carbamate prodrug also showed to be stable in rat serum. However, the carbonate and the ester prodrug release at various rates in serum presumably owing to the presence of several different classes of esterase. The biological activities of the drug conjugates correlate with the stability of their cleavable linkers observed in serum.Conclusion: The targeted and selective delivery of potent Nampt inhibitors to cancer cells is a potentially new route for the treatment of many cancers. These prodrugs linked to small cancer-associated peptides may be optimum for their use as targetable Nampt inhibitors. Keywords: carboranes, Nampt, cancer, prodrugs, cleavable linker

Bis‐carborane‐substituted benzo[1, 2‐b:4, 5‐b′]dithiophenes (DCB‐R, where R = H, tBu) were synthesized and characterized. Their three‐dimensional conformations were tuned by introducing the tert‐butyl substituent at the para‐positions of the phenyl rings. Both molecules showed emission enhancement behavior, especially in the solid state. The emission quantum efficiencies were over 0.90 in the crystalline state. Moreover, it was shown that the efficiency of DCB‐tBu was over 0.70 in the amorphous state. From structural analyses and mechanistic investigations, it was proposed that the tert‐butyl substituents play a critical role in the formation of the trans‐conformation followed by suppression of aggregation‐caused quenching because of the o‐carborane units located at each plane of the benzodithiophene ring.

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.

This work deals with carborane and metallacarborane clusters, in terms of their fundamental chemistry and complexation with cyclodextrins, and in the context of emerging pharmacophores applicable in medicinal chemistry. Arguably, the most important part of this work is the preparation of cobalt bis(dicarbollide) sulfamide derivatives. The sulfamido group is attached to the metallacarborane carbon vertex by an alkyl chain that may be modified in its length. This was accomplished by, firstly, the abstraction of the acidic hydrogen, located on the {CH}-vertex from the metallacarborane, by reaction with lithium base, followed by, secondly, reaction with electrophilic agents (PFA, oxirane and oxetane), which leads to a cascade of reactions to give the desired sulfamide derivatives. These compounds were then tested by collaborators in other institutes for in vitro and in vivo activity towards Carbonic Anhydrase IX (CA IX), which is an enzyme associated with tumour growth. In vivo tests on mice have shown that these types of substances are able to effectively reduce tumour size by 30%. The synthetic research continued with the preparation of sulfonamide compounds of the isomers of the carborane series. The reactions began exclusively with propylhydroxy carborane starting materials, which provide optimum...

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.

Grubbs-catalyzed ring-opening metathesis polymerization (ROMP) of carborane- and phosphonate-containing monomers has been used for the generation of hybrid block copolymers. Molecular weights with Mn of 50,000 g/mol were readily obtained with polydispersity index values, Đ, between 1.03&ndash, 1.08. Reaction of the phospha ester and carborane substituted oxanorbornene block copolymer with trimethylsilyl bromide led to a new polymer with phosphonic acid functionalities. In application studies, the phospha-carborane functionalized block polymer was tested as heat resistance material. Thermal stability was investigated by thermal gravimetric analysis (TGA) and microscale combustion calorimetry (MCC) analysis. Thermal treatment and ceramic yield under air were directly correlated to the carborane content of the block copolymer. However, phosphorus content in the polymer was more crucial for the char residues when heated under nitrogen atmosphere. The peak heat release rate (PHRR) increased as the number of phosphonate functionalities increased. However, corresponding phosphonic acid derivatives featured a lower heat release rate and total heat release. Moreover, the phosphonic acid functionalities of the block copolymer offer efficient chelating capabilities for iron nanoparticles, which is of interest for applications in biomedicine in the future. The complexation with iron oxide nanoparticles was studied by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP&ndash, MS).

Grubbs-catalyzed ring-opening metathesis polymerization (ROMP) of carborane- and phosphonate-containing monomers has been used for the generation of hybrid block copolymers. Molecular weights with Mn of 50,000 g/mol were readily obtained with polydispersity index values, Đ, between 1.03–1.08. Reaction of the phospha ester and carborane substituted oxanorbornene block copolymer with trimethylsilyl bromide led to a new polymer with phosphonic acid functionalities. In application studies, the phospha-carborane functionalized block polymer was tested as heat resistance material. Thermal stability was investigated by thermal gravimetric analysis (TGA) and microscale combustion calorimetry (MCC) analysis. Thermal treatment and ceramic yield under air were directly correlated to the carborane content of the block copolymer. However, phosphorus content in the polymer was more crucial for the char residues when heated under nitrogen atmosphere. The peak heat release rate (PHRR) increased as the number of phosphonate functionalities increased. However, corresponding phosphonic acid derivatives featured a lower heat release rate and total heat release. Moreover, the phosphonic acid functionalities of the block copolymer offer efficient chelating capabilities for iron nanoparticles, which is of interest for applications in biomedicine in the future. The complexation with iron oxide nanoparticles was studied by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP–MS).

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.

In this work we present a computational analysis of a new family of magnetic Co(II) single-ion complexes with large magnetic anisotropy based on icosahedral and octahedral carborane ligands. In particular, we extend our previous computational work [Alcoba et al. Inorg. Chem. 57, 7763 (2018)] on mononuclear Co(II) complexes with 1,2-(HS)2-1,2-C2B10H10 and 9,12-(HS)2-1,2-C2B10H10 icosahedral o-carborane ligands to a larger set of complexes where the Co(II) ion is doubly chelated by those ligands and by other two positional isomers belonging to the 1,2-dicarba-closo-dodecaborane family. We also describe Co(II) complexes with octahedral ligands derived from 1,2- dicarba-closo-hexaborane and study the effects of replacing a thiol group by a hydroxy one in both polyhedral geometries, as well as the influence of the position of the carbon atoms. Analyzing the results for a total of 20 complexes, our results show that carborane-based Co(II) single-ion compounds present a distorted tetrahedral geometry, high spin ground states, and high values for the magnetic anisotropy parameters. We point out which of these would be suitable candidates to be synthesized and used as molecular magnets., Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas