Clinically there is a need for local anesthetics with a greater specificity of action on target cells and longer duration. We have synthesized a series of local anesthetic derivatives we call boronicaines in which the aromatic phenyl ring of lidocaine was replaced with ortho-, meta-, C,C'-dimethyl meta- and para-carborane clusters. The boronicaine derivatives were tested for their analgesic activity and compared with lidocaine using standard procedures in mice following a plantar injection. The compounds differed in their analgesic activity in the following order: ortho-carborane = C,C'-dimethyl meta-carborane > para-carborane > lidocaine > meta-carborane derivative. Both ortho-boronicaine and C,C'-dimethyl meta-boronicaine had longer durations of analgesia than lidocaine. Differences in analgesic efficacies are rationalized by variations in chemical structure and protein binding characteristics.
The palladium-catalyzed Buchwald-Hartwig amination of B-iodocarborane by various azoles and amines is described for the first time. The reactions of 2-iodo-p-carborane with indole, imidazole, benzimidazole, or carbazole in the system Pd(dba) 2 -BINAP-Bu t ONa in dioxane at 100 °C gave 2-pcarboranyl derivatives of these azoles in high yields together with 2-hydroxy-p-carborane as a side product. The reactions of 2-iodo-p-carborane with aromatic amines in the same system gave the amination products in 60-70% yields and also were accompanied by the formation of hydroxy derivatives (up to 30% yields). In a special investigation it was shown that the base Bu t ONa was responsible for its formation. The principle possibility of the amination of 2-iodo-p-carborane by morpholine (with 30% yield) as an example of aliphatic amination was shown. The structures of N- (1,12-dicarba-closo-dodecaboran-2-yl) 4), and 2-hydroxy-1,12-dicarba-closo-dodecaborane (5) have been established by X-ray diffraction studies.
Thermal decomposition of four tertiary N‐(2‐methylpropyl)‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐N‐oxyl (SG1)‐based alkoxyamines (SG1‐C(Me)2‐C(O)‐OR, R = Me, tBu, Et, H) has been studied at different experimental conditions using 1H and 31P NMR spectroscopies. This experiment represents the initiating step of methyl methacrylate polymerization. It has been shown that H‐transfer reaction occurs during the decomposition of three alkoxyamines in highly degassed solution, whereas no products of H‐transfer are detected during decomposition of SG1‐MAMA alkoxyamine. The value of the rate constant of H‐transfer for alkoxyamines 1 (SG1‐C(Me)2‐C(O)‐OMe) and 2 (SG1‐C(Me)2‐C(O)‐OtBu) has been estimated as 1.7 × 103 M−1s−1. The high influence of oxygen on decomposition mechanism is found. In particular, in poorly degassed solutions, nearly quantitative formation of oxidation product has been observed, whereas at residual pressure of 10−5 mbar, the main products originate from H‐atom transfer reaction. The acidity of the reaction medium affects the decomposition mechanism suppressing the H‐atom transfer. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
The palladium-catalyzed amidation of B-iodocarboranes by various amides is described for the first time. The reactions of 2-iodo-1,12-dicarba-closo-dodecaborane (2-iodo-p-carborane) with acetamide, 2-pyrrolidinone, caprolactam, p-methylbenzamide, and 2-phenylacetamide using the system Pd(dba)2/BINAP/NaH (dba = dibenzylideneacetone; BINAP = rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) in dioxane at 100 °C gave 2-p-carboranyl derivatives of these amides in good to high yields. Similar reactions of 9-iodo-1,7-dicarba-closo-dodecaborane (9-iodo-m-carborane) with corresponding amides afforded 9-m-carboranyl derivatives in good to high yields. The structures of N-(1,12-dicarba-closo-dodecaboran-2-yl)pyrrolidin-2-one (5), N-(1,7-dicarba-closo-dodecaboran-9-yl)acetamide (6), and N-(1,7-dicarba-closo-dodecaboran-9-yl)-2-phenylacetamide (7) have been established by X-ray diffraction studies.
Site Directed Spin Labeling (SDSL) combined with EPR spectroscopy is a very powerful approach to investigate structural transitions in proteins in particular flexible or even disordered ones. Conventional spin labels are based on nitroxide derivatives leading to classical 3-line spectra whose spectral shapes are indicative of the environment of the labels and thus constitute good reporters of structural modifications. However, the similarity of these spectral shapes precludes probing two regions of a protein or two partner proteins simultaneously. To overcome the limitation due to the weak diversity of nitroxide label EPR spectral shapes, we designed a new spin label based on a β-phosphorylated nitroxide giving 6-line spectra. This paper describes the synthesis of this new spin label, its grafting at four different positions of a model disordered protein able to undergo an induced α-helical folding and its characterization by EPR spectroscopy. For comparative purposes, a classical nitroxide has been grafted at the same positions of the model protein. The ability of the new label to report on structural transitions was evaluated by analyzing the spectral shape modifications induced either by the presence of a secondary structure stabilizer (trifluoroethanol) or by the presence of a partner protein. Taken together the results demonstrate that the new phosphorylated label gives a very distinguishable signature which is able to report from subtle to larger structural transitions, as efficiently as the classical spin label. As a complementary approach, molecular dynamics (MD) calculations were performed to gain further insights into the binding process between the labeled NTAIL and PXD. MD calculations revealed that the new label does not disturb the interaction between the two partner proteins and reinforced the conclusion on its ability to probe different local environments in a protein. Taken together this study represents an important step forward in the extension of the panoply of SDSL-EPR approaches.
A novel route for synthesis of B‐mercaptocarboranes is described. The reaction proceeds through Pd‐catalyzed iodine exchange with the sulfur nucleophile TIPS–SH in mono‐ and diiodinated ortho‐, meta‐, and para‐carboranes. Self‐assembled monolayers of selected B‐mercaptocarboranes on a gold surface were analyzed by X‐ray photoelectron spectroscopy and their water contact angles were assessed.
For the first time, the palladium-catalyzed etheration of 2-iodo-p-carborane with phenolates and alkoxides has been demonstrated. The reactions of 2-iodo-1,12-dicarba-closo-dodecaborane (2-iodop-carborane) with sodium salts of phenol, p-cresol, Rand β-naphthol, 3-methyl-4-chlorophenol, and 3,4-dimethylphenol using the Pd(dba) 2 /BINAP (dba = dibenzylideneacetone; BINAP = rac-2,2 0 -bis-(diphenylphosphino)-1,1 0 -binaphthyl) system in dioxane at 90 °C afforded the corresponding 2p-carboranyl aryl ethers in good to high yields. 2-Methoxy-p-carborane and 2-ethoxy-p-carborane have also been obtained in good yield. The structures of 2-(4-methylphenoxy)-p-carborane and 2-methoxyp-carborane have been established by X-ray diffraction studies.
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