Monomers containing substrate or inhibitor residues for copper amine oxidases and their hydrophilic beaded resins designed for enzyme interaction studies

Five styrenic monomers, four with aminoalkyl residues typical of copper containing amine oxidase substrates and one with a 2,6-dialkoxybenzylamine residue which mimics previously prepared selective substrate-like benzylamine oxidase inhibitors, have been synthesized and transformed into radical homopolymers, copolymers with N,N-dimethylacrylamide (DMAA), and hydrophilic beaded resins, designed for enzyme interaction studies aimed in finding new materials for highly biospecific chromatographic separations. The five monomers have given beaded resins of 125-500 μm swellable in water with a volume increase of 1200-1500%. The four aminoalkyl monomers have given water soluble copolymers some of which are good substrates of benzylamine oxidase (BAO), diamine oxidase (DAO) and lysyl oxidase (LO), up to 9.7 times better than elastin for LO.     

Regioselective Insertion of o‐Carborynes into the α‐CH Bond of Tertiary Amines: Synthesis of α‐Carboranylated Amines

o‐Carboryne can undergo α‐C? H bond insertion with tertiary amines, thus affording α‐carboranylated amines in very good regioselectivity and isolated yields. In this process, the nucleophilic addition of tertiary amines to the multiple bond of o‐carboryne generates a zwitterionic intermediate. An intramolecular proton transfer, followed by a nucleophilic attack leads to the formation of the final product. Thus, regioselectivity is highly dependent upon the acidity of α‐C? H proton of tertiary amines. This approach serves as an efficient methodology for the preparation of a series of 1‐aminoalkyl‐o‐carboranes.     

A NEW APPLICATION OF INORGANIC CLUSTER,CARBORANES FOR MEDICINAL DRUG DESIGN AND MOLECULAR CONSTRUCTION

The inorganic cage compounds, dicarba-closo-dodecaboranes (carboranes), are chemical building blocks of remarkable thermal and chemical stability, with spherical geometry and exceptional hydrophobic character. We have focused on medicinal drug design using carboranes as a hydrophobic pharmacophore and have developed a potent estrogen agonist, BE120. We also have applied carboranes for structural chemistry, utilizing their specific three-dimensional character to obtain multilayer aromatic structures.     

Regioselective Insertion of o‐Carborynes into the α‐C?H Bond of Tertiary Amines: Synthesis of α‐Carboranylated Amines

o‐Carboryne can undergo α‐C H bond insertion with tertiary amines, thus affording α‐carboranylated amines in very good regioselectivity and isolated yields. In this process, the nucleophilic addition of tertiary amines to the multiple bond of o‐carboryne generates a zwitterionic intermediate. An intramolecular proton transfer, followed by a nucleophilic attack leads to the formation of the final product. Thus, regioselectivity is highly dependent upon the acidity of α‐C H proton of tertiary amines. This approach serves as an efficient methodology for the preparation of a series of 1‐aminoalkyl‐o‐carboranes.     

Recent Progress in the Chemistry of Supercarboranes

The chemistry of boron clusters has been dominated by icosahedral carboranes for over half a century. Only in recent years has significant progress been made in the chemistry of supercarboranes (carboranes with more than 12 vertices). A number of CAd (carbon‐atoms‐adjacent) 13‐ and 14‐vertex carboranes, and CAp (carbon‐atoms‐apart) 13‐vertex carboranes as well as their corresponding 14‐ and 15‐vertex metallacarboranes have been successfully prepared and structurally characterized. This breakthrough relied on the use of CAd nido‐carborane dianions as starting materials. These supercarboranes can undergo single‐electron reduction to give stable supercarborane radical monoanions with [2n+3] framework electrons, and electrophilic substitution reaction to afford hexasubstituted supercarboranes. They can react with nucleophiles to offer monocarba‐closo‐dodecaborate monoanions from cage‐carbon extrusion reactions. Their unique chemical properties make the chemistry of supercarboranes distinct from that of their 12‐vertex analogues. These studies open up new possibilities for the development of polyhedral clusters of extraordinary size. This focus review offers an overview of recent advances in this growing research field.     

Aminoalkyl radicals: direct observation and reactivity toward oxygen, 2,2,6,6-tetramethylpiperidine-N-oxyl, and methyl acrylate

The reactivity of 11 aminoalkyl radicals toward different additives [oxygen, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), and methyl acrylate (MA)] has been investigated through laser flash photolysis and quantum mechanical calculations. The transient absorption spectra of the radicals were recorded: good agreement was found with the spectra calculated by using quantum mechanical calculations. All the interaction rate constants were measured. A large range of values are obtained: (0.04-3) x 10(9) M(-1) s(-1) for O2, (0.002-5) x 10(8) M(-1) s(-1) for TEMPO, and (<0.004-2) x 10(7) M(-1) s(-1) for MA. Generation of the decarboxylated aminoalkyl radical derived from N-phenylglycine was unambiguously demonstrated. It was clearly found that both the addition to oxygen and the recombination with TEMPO were strongly governed by the reaction exothermicity. On the other hand, both polar and enthalpy factors have a large influence on the rate constants of the addition reaction to the acrylate unit, which were ranging over at least 4 orders of magnitude. This paper provides a set of new data to characterize the structure/reactivity relationships of aminoalkyl radicals.     

Carboranes as a Tool to Tune Phosphorescence

Phosphorescent transition‐metal complexes (PTMCs) have attracted great interest because of their excellent properties which may lead to promising applications in optoelectronics. In recent years, carboranes have been demonstrated to be a novel and effective tool to tune phosphorescence of PTMCs. This Concept article deals with the advances of carborane‐functionalized PTMCs for potential optical applications. The discussions are focused on the design strategies and synthetic procedures leading to carborane‐functionalized PTMCs, the influence of carboranes on the optical properties of PTMCs, and the promising optical applications of this interesting class of phosphorescent materials.     

Photoarylation of Iodocarboranes with Unactivated (Hetero)Arenes: Facile Synthesis of 1,2‐[(Hetero)Aryl]n‐o‐Carboranes (n=1,2) and o‐Carborane‐Fused Cyclics

Photoarylation of iodocarboranes with unactivated arenes/heteroarenes at room temperature has been achieved, for the first time, thus leading to the facile synthesis of a large variety of cage carbon mono(hetero)arylated and di(hetero)arylated o‐carboranes. This work represents a clean, efficient, transition‐metal‐free, and cheap synthesis of functionalized carboranes, which has significant advantages over the known methods.     

实时直接分析高分辨质谱技术研究碳硼烷类化合物

该文运用高分辨质谱技术对实时直接分析(Direct analysis in real time,DART)离子化条件下碳硼烷化合物的质谱行为进行了研究,对碳硼烷化合物DART高分辨质谱中所得到的同位素峰簇进行了表征与归属.研究结果表明,选取的碳硼烷化合物在DART负离子条件下均能得到较好的质谱信号,这可能与硼笼结构的"...     

Novel approach to aminocarboranes by mild amidation of selected iodo-carboranes

A mild protocol for the palladium-catalyzed Buchwald-Hartwig amidation of icosahedral carboranes is described. Employing 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (1) as a ligand and K(3)PO(4) as a base, benzamide, trifluoroacetamide, acetamide, and formamide were coupled to a series of mono- and di-iodo carboranes furnishing the respective carborane derivatives in good to excellent yields. Subsequent base-mediated saponification of the trifluoroacetamide derivatives was shown to provide the free aminocarboranes. The structures of N-(1,7-dicarba-closo-dodecaboran-9-yl)benzamide (8a), N-(1,7-dicarba-closo-dodecaboran-9-yl)trifluoroacetamide (8b), N-(1,12-dicarba-closo-dodecaboran-2-yl)benzamide (10a), N-(1,2-dicarba-closo-dodecaboran-9-yl)benzamide (12a), N-(1,2-dicarba-closo-dodecaboran-9-yl)acetamide (12c), N-(1,2-dicarba-closo-dodecaboran-9-yl)formamide (12d), N-(1,2-dicarba-closo-dodecaboran-3-yl)benzamide (13a), N,N'-(1,7-dicarba-closo-dodecaboran-9,10-diyl)dibenzamide (15a), and N,N'-(1,7-dicarba-closo-dodecaboran-9,10-diyl)bis(trifluoroacetamide) (15b) have been established through X-ray single-crystal diffraction studies.     

4-N,N-Dimethylamino-4'-Isopropylbenzophenone as polymerization photoinitiator. Effect of solvent and photoinitiator concentration on its photoreactivity and on the polymerization process

Several kinetics aspects of the methyl methacrylate (MMA) polymerization using 4-dimethylamino-4'-isopropylbenzophenone (PI) as photoinitiator have been studied. The order of the polymerization reaction with respect to monomer and initiator concentrations have been investigated, as well as the polymerization behavior under well-stirred and unstirred conditions; values of initiation quantum yield (?_i) and k_p/k_t^1/2 have also been determined. It has been found that the nature of the polymerization-initiating radicals depends on the type of solvent and the photoinitiator concentration ([PI]). In cyclohexane solution and at low [PI] (< 5 x 10^-5M), the cyclohexyl radical is practically the only polymerization initiating radical, while at higher [PI] both radicals, cyclohexyl and the aminoalkyl derived from PI, participate in the initiation step, increasing the participation of the later as the [PI] increases. When benzene is used as solvent both phenyl and aminoalkyl radicals participate in the initiation step at any [PI] employed. Efficiencies of the radicals derived from solvent and photoinitiator have been determined.     

Competition between Halogen,Hydrogen and Dihydrogen Bonding in Brominated Carboranes

Halogen bonds are a subset of noncovalent interactions with rapidly expanding applications in materials and medicinal chemistry. While halogen bonding is well known in organic compounds, it is new in the field of boron cluster chemistry. We have synthesized and crystallized carboranes containing Br atoms in two different positions, namely, bound to C‐ and B‐vertices. The Br atoms bound to the C‐vertices have been found to form halogen bonds in the crystal structures. In contrast, Br atoms bound to B‐vertices formed hydrogen bonds. Quantum chemical calculations have revealed that halogen bonding in carboranes can be much stronger than in organic architectures. These findings open new possibilities for applications of carboranes, both in materials and medicinal chemistry.     

General Access to Aminobenzyl‐o‐carboranes as a New Class of Carborane Derivatives: Entry to Enantiopure Carborane–Amine Combinations

The convenient synthesis of original aminobenzyl‐o‐carboranes, which represent a new class of nitrogenated carborane derivatives, is described. These novel compounds have been efficiently prepared starting from commercially available aromatic aldehydes and monosubstituted o‐carboranes via carboranyl alcohols and chlorides as intermediates. The key step of this methodology is a selective nucleophilic amination under mild conditions that allows the formation of the expected amines while limiting the partial deboronation of the carborane cluster. This general strategy has been applied to the preparation of a wide variety of aminobenzyl‐o‐carboranes. The extension of this pathway to the synthesis of enantiopure carborane–amine combinations is also described.     

DFT study on the second‐order nonlinear optical property of 12‐vertex close‐carborane derivatives

Density functional theory (DFT) BHandHLYP method based on the 6‐31G(d) level was employed to optimize the structures of 12‐vertex substituted carboranes. The finite field (FF) method was adopted to study their second‐order nonlinear optical coefficients. Moreover, the electron spectra of systems were analyzed. The results show carboranes with alkali‐metal substituted have considerably large first hyperpolarizability (β_tot) values which is 2–3 order of magnitude larger than that of unsubstituted carborane (14.5 a.u). For halogen and organic group substituted systems, however, the β_tot values are only enhanced by one order of magnitude. The β values of carboranes obviously enhance after alkali‐metal substitution. This study may evoke the possibility to explore a new thriving area, i.e., alkali‐metal substituted carboranes for NLO application. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Synthesis of small carboranylsilane dendrons as scaffolds for multiple functionalizations

Small carbosilane dendrons in which a closo-carborane is located at the focal point have been prepared by a sequence of steps involving hydrosilylation and reduction reactions. These compounds are used as scaffolds for peripheral functionalization with styrene, chlorovinylstyrene, or suitable carboranes, while keeping the C(cluster)-Si (C(c)-Si) bond. Modification of the core by reduction of the carborane with Mg/BrCH2CH2Br was also achieved.     

碳硼烷结构规则的量子化学计算

本文对一系列封闭型C_nB_5-n(n=0～5)和C_nB_6-n(n=0～6)碳硼烷骨架及巢型C₄B_5-n(n=0～5)碳硼烷骨架进行了EHMO量子化学计算,根据计算结果讨论了碳硼烷的结构规则.     

Novel methodologies for the synthesis of functionalized lipophilic carboranes

Novel synthetic protocols for the synthesis of lipophilic carboranes were developed utilizing two C? C bond forming reactions, namely Baylis–Hillman and enynedioate cycloaddition reactions. Some of these carboranes were converted into further functionalized carboranes via nucleophilic allylic isomerization. Copyright © 2009 John Wiley & Sons, Ltd.     

Structures and Syntheses of Carboranes

Following a discussion of bonding, the structures of the known carboranes of the clovo type and of the incompletely condensed types are described; the recently discovered carboranes with high carbon contents, such as tetracarbahexaborane (“boracarbane”) are also discussed. The preparation of carboranes from polyboranes and the possibility of obtaining organo carboranes from organoboranes are then described. Some rearrangements which take place within the carborane skeleton are also mentioned.     

Some aspects of the chemical behavior of icosahedral carboranes

Abatract  Important features of the chemical behavior of icosahedral carboranes are considered. The ways of introducing functional groups at the carbon and boron atoms of carboranes by conventional methods of organic chemistry and methods applicable only to carboranes are discussed. The latter methods include transformations of dicarbadodecaborate(14) dianions. Examples of the enantiomeric resolution of optically active carboranes, whose chirality is associated with the molecular asymmetry, are given. The diversity of chemical transformations of carboranes is exemplified by intramolecular nucleophilic rearrangements, cross-coupling reactions, and the formation of chelate metallacycles. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 801–822, April, 2008.     

Nucleophilic Attack of α‐Aminoalkyl Radicals on Carbon?Nitrogen Triple Bonds to Construct α‐Amino Nitriles: An Experimental and Computational Study

A new reactivity pattern of α‐aminoalkyl radicals, involving nucleophilic attack on C?N triple bonds under thermal conditions, has been developed to construct α‐amino nitriles. In contrast to previous C? H functionalization of tertiary amines involving α‐aminoalkyl radicals, this methodology does not require the use of photocatalytic conditions or a transition‐metal catalyst. Inexpensive and nontoxic phenylacetonitrile was chosen as cyano source for this α‐aminonitrile forming reaction. A plausible mechanism is proposed based upon experimental and computational results. An α‐aminoalkyl radical intermediate and benzoyl cyanide have been shown to be key intermediates in this green and mild radical process. Nucleophilic attack of the α‐aminoalkyl radical on the C?N bond of PhCOCN followed by an elimination step forms the desired α‐aminonitrile and an acyl radical.