Trimethylammonium Salts Research Articles

Cobaltabis(Dicarbollide) [o-COSAN]- for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model.

Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3'-Co(C2B9H11)2], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of 10B-enriched trimethylammonium salt of nido-[7,8-C210B9H12]-o-carborane, along with the cesium and sodium salts of [o-10COSAN] cobaltabis(dicarbollide) are reported here for the first time. Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[10B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Na[o-10COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-10COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Na[o-10COSAN] would be potentially useful to treat head and neck cancer with BNCT.

Synthesis, Electronic, and Antibacterial Properties of 3,7-Di(hetero)aryl-substituted Phenothiazinyl N-Propyl Trimethylammonium Salts.

In this study, a library of 3,7-di(hetero)aryl-substituted 10-(3-trimethylammoniumpropyl)10H-phenothiazine salts is prepared. These title compounds and their precursors are reversible redox systems with tunable potentials. The Hammett correlation gives a very good correlation of the first oxidation potentials with σp parameters. Furthermore, the title compounds and their precursors are blue to green-blue emissive. Screening of the salts reveals for some derivatives a distinct inhibition of several pathogenic bacterial strains (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Aconetobacter baumannii, and Klebsiella pneumoniae) in the lower micromolar range.

Allylation of C-, N-, and O-Nucleophiles via a Mechanochemically-Driven Tsuji-Trost Reaction Suitable for Late-Stage Modification of Bioactive Molecules.

We present the first solvent-free, mechanochemical protocol for a palladium-catalyzed Tsuji-Trost allylation. This approach features exceptionally low catalyst loadings (0.5 mol %), short reaction times (<90 min), and a simple setup, eliminating the need for air or moisture precautions, making the process highly efficient and environmentally benign. We introduce solid, nontoxic, and easy-to-handle allyl trimethylammonium salts as valuable alternative to volatile or hazardous reagents. Our approach enables the allylation of various O-, N-, and C-nucleophiles in yields up to 99 % even for structurally complex bioactive compounds, owing to its mild conditions and exceptional functional group tolerance.

Allylation of C-, N-, and O-Nucleophiles via a Mechanochemically-Driven Tsuji-Trost Reaction Suitable for Late-Stage Modification of Bioactive Molecules.

We present the first solvent-free, mechanochemical protocol for a palladium-catalyzed Tsuji-Trost allylation. This approach features exceptionally low catalyst loadings (0.5 mol %), short reaction times (<90 min), and a simple setup, eliminating the need for air or moisture precautions, making the process highly efficient and environmentally benign. We introduce solid, nontoxic, and easy-to-handle allyl trimethylammonium salts as valuable alternative to volatile or hazardous reagents. Our approach enables the allylation of various O-, N-, and C-nucleophiles in yields up to 99 % even for structurally complex bioactive compounds, owing to its mild conditions and exceptional functional group tolerance.

Trimethyl Ammonium‐Assisted Interfacial Modification for Efficient and Stable Wide‐Bandgap Perovskite Solar Cells

Wide‐bandgap (WBG) perovskite solar cells (PSCs) are acknowledged as promising candidates for tandem solar cells and building photovoltaics. It is well known that cesium‐based all‐inorganic halide WBG perovskites possess the comparable optoelectronic properties as the organic–inorganic counterparts, but exhibit superior thermal stability. Among them, CsPbIBr2 is considered a feasible material for tandem solar cells after balancing the bandgap and stability of the inorganic perovskite. However, CsPbIBr2 PSCs are often subjected to drastic interfacial charge recombination especially in carbon‐based device structure derived from the chemical bonding defects (i.e., uncoordinated Pb2+) naked on CsPbIBr2 soft lattice, which dramatically limits overall efficiency of CsPbIBr2 WBG PSCs. Herein, a trimethyl ammonium salt hexyltrimethylammonium bromide is presented for CsPbIBr2/carbon interfacial modification. Benefiting from the −N+(CH3)3 passivation effect and −C6H13 hydrophobic alkyl chain, the optimal device with highly smooth morphology and sufficient charge extraction exhibits a champion power conversion efficiency of 11.24% and improved long‐term stability with 99.7% and 79.7% efficiency retention under dry air atmosphere and continuous 85 °C thermal stress, indicating the valuable potential application of the lattice solidified CsPbIBr2 WBG PSCs.

Synthesis of Benzyl Thioethers by C−S Coupling of Benzylic Trimethylammonium Salts and Sulfonyl Chlorides

AbstractA facile and efficient method to synthesize thioethers from sulfonyl chlorides and benzylic trimethylammonium salts is presented. This protocol provides a simple and direct approach to realize the reductive coupling reaction of readily available sulfonyl chlorides with benzyl ammonium salts in the presence of triphenylphosphine along with base via C−N cleavage of benzyl ammonium salts. This reaction features mild conditions and good substrate compatibility to afford thioethers in moderate to good yields.

Suzuki–Miyaura Cross-Coupling of 2-Pyridyl Trimethylammonium Salts by N–C Activation Catalyzed by Air- and Moisture-Stable Pd–NHC Precatalysts: Application to the Discovery of Agrochemicals

We report the first Suzuki-Miyaura cross-coupling of 2-pyridyl ammonium salts by highly selective N-C activation catalyzed by air- and moisture-stable Pd(II)-NHC (NHC = N-heterocyclic carbene) precatalysts. The use of well-defined and highly reactive [Pd(IPr)(3-CF3-An)Cl2] (An = aniline) or [Pd(IPr)(cin)Cl] (cin = cinnamyl) Pd(II)-NHC catalysts permits an exceptionally broad scope of the cross-coupling to furnish valuable biaryl and heterobiarylpyridines that are ubiquitous in medicinal chemistry and agrochemistry research. The overall process leverages the Chichibabin C-H amination of pyridines with N-C activation to enable an attractive strategy to the 2-pyridyl problem. The utility of the method to the discovery of potent agrochemicals is presented. Considering the importance of 2-pyridines and the versatility of N-C activation methods, we envision that this new C-H/N-C activation strategy will find broad application.

Half-Sandwich Nickelacarboranes Derived from [7-(MeO(CH2)2S)-7,8-C2B9H11

New carboranyl thioethers 1-MeO(CH2)nS-1,2-C2B10H11 (n = 2, 3) were prepared by the alkylation of the trimethylammonium salt of 1-mercapto-ortho-carborane with 1-bromo- 2-methoxyethane and 1-bromo-3-methoxypropane, respectively. Their deboronation with cesium fluoride in ethanol gave the corresponding nido-carboranes Cs[7-MeO(CH2)nS-7,8-C2B9H11] (n = 2, 3). The reactions of Cs[7-MeO(CH2)2S-7,8-C2B9H11] with various nickel(II) phosphine complexes [(dppe)NiCl2] and [(R’R2P)2NiCl2] (R = R’ = Ph, Bu; R = Me, R’ = Ph; R = Ph, R’ = Me, Et) were studied and a series of nickelacarboranes 3,3-dppe-1-MeO(CH2)2S-closo-3,1,2-NiC2B9H10 and 3,3- (R’R2P)2-1-MeO(CH2)2S-closo-3,1,2-NiC2B9H10 (R = R’ = Bu; R = Me, R’ = Ph; R = Ph, R’ = Me, Et) was prepared. The molecular crystal structure of 3,3-dppe-1-MeO(CH2)2S-closo-3,1,2-NiC2B9H10 was determined by single-crystal X-ray diffraction.

A Practically Unified Electrochemical Strategy for Ni-Catalyzed Decarboxylative Cross-Coupling of Aryl Trimethylammonium Salts.

By merging electrocatalysis and nickel catalysis, a unified strategy has been successfully applied to achieve the decarboxylative cross-coupling of four types of α-oxocarboxylic acids and their derivatives with aryl trimethylammonium salts under mild conditions. Our strategy provides a practical way for preparing aryl ketones, amides, esters, or aldehydes.

Microfabricated Liquid Junction Capillary Electrophoresis-Mass Spectrometry Interface.

Coupling of capillary electrophoresis (CE) with mass spectrometry (MS) represents a powerful combination for performing rapid, efficient, and sensitive analysis of a variety of compounds. Here we describe a construction, operation, and application of a microfabricated liquid junction CE-MS interface. The interface is designed as a microfabricated unit with an integrated liquid junction and electrospray tip made from polyimide, which is positioned in a plastic connection block securing the separation CE capillary and attachable to the CE instrument. The application was demonstrated by CE-MS analysis of dextran oligomers labeled by (2-aminoethyl)trimethylammonium (AETMA) salt.

Cyanation and cyanomethylation of trimethylammonium salts via electrochemical cleavage of C–N bonds

A practical and mild electrochemical protocol for cyanation and cyanomethylation of trimethylammonium salts has been developed.

One-pot nickel-catalyzed cross-coupling of (Het)arylammonium salts prepared in situ and organozinc reagents

A nickel-catalyzed arylation of aromatic amines using arylzinc reagents with trimethylammonium salts formed in situ is developed. Compared with previous systems using ammonium salts as the starting materials and complexes of pre-prepared nickel catalysts, this reaction directly employed an N, N-dimethyl(het)arylamine as the coupling partner and commercial Ni(COD)2 /TMEDA as the catalyst, greatly simplifying the experimental procedure, decreasing the cost, and being especially suitable for scale-up production processes.

Synthesis of Dibenzylic Diselenides from Elemental Selenium and Benzylic Quaternary Ammonium Salts

AbstractAbstract: Substituted dibenzyl diselenides are synthesized in good yields (74–91 %) by SN2 nucleophilic substitution of benzylic trimethylammonium salts and diselenide dianion (Se2−), in situ generated from elemental selenium, under basic conditions. Highly enantiopure dibenzylic diselenides (95–98 % ee) with reverse configurations to their enantioenriched quaternary ammonium salts are obtained, if benzylic quaternary ammonium salts, synthesized from enantiomerically enriched amines, are used.

Unusual Deoxidative Coupling Reaction of β-Sulfinyl Esters with Benzylic Trimethylammonium Salts.

A KOH-promoted unusual deoxidative coupling reaction of β-sulfinyl esters with benzylic trimethylammonium salts to produce thioethers is discovered for the first time. If quaternary ammonium salts synthesized from enantiomerically enriched amines are adopted, highly enantiomerically enriched benzyl thioethers (>95-99% ee) with configurations opposite to those of the enantiomerically enriched amines are obtained.

Synthesis of cholesterol derivatives based on closo- and nido-carboranes

1-(3-Butyn-1-ylthio)-1,2-dicarba-closo-dodecaborane was synthesized by the alkylation of 1-mercapto-1,2-dicarba-closo-dodecaborane trimethylammonium salt with butyn-3-yl methanesulfonate. The deboronation reaction of this compound gave the corresponding derivative based on nido-carborane, namely, 7-(3-butyn-1-ylthio)-7,8-dicarba-undecaborate anion. 1,4-Disubstituted 1,2,3-triazoles based on closo- and nido-carboranes were synthesized by the CuI-catalyzed 1,3-dipolar [3+2] cycloaddition reaction of the acetylene derivatives of closo- and nido-carboranes with azidocholesterol.

Radical generation from electroreduction of aryl and benzyl ammonium salts: synthesis of organoboronates

We report a direct electrocatalytic borylation of aryl and benzyl trimethylammonium salts with bis(pinacolato)diboron at room temperature.

“Free of Base” Sulfa-Michael Addition for Novel o-Carboranyl-DL-Cysteine Synthesis

The sulfa-Michael addition reaction was applied for the two-step synthesis of o-carboranyl cysteine 1-HOOCCH(NH2)CH2S-1,2-C2B10H11 from the trimethylammonium salt of 1-mercapto-o-carborane and methyl 2-acetamidoacrylate. To avoid the decapitation of o-carborane into its nido-form, the “free of base” method under mild conditions in a system of two immiscible solvents toluene-H2O was developed. The replacement of H2O by 2H2O resulted in carboranyl-cysteine containing a deuterium label at the α-position of the amino acid 1-HOOCCD(NH2)CH2S-1,2-C2B10H11. The structure of the protected o-carboranyl cysteine was determined by single-crystal X-ray diffraction. The obtained compounds can be considered as potential agents for the Boron Neutron Capture Therapy of cancer.

No-additive salting-out liquid-liquid extraction-A tool for purification of positively charged compounds from highly salted reaction mixtures.

A novel and original application of salting-out assisted liquid-liquid extraction is presented. This technique was used to purify the final reaction products (quaternary ammonium salts) from unreacted components and by-products present in multiple excesses. The partition of two structurally related compounds as (2-aminoethyl)trimethylammonium salt (a labeling reagent) and a derivative of [2-(imidazoline-1-yl)ethyl]trimethylammonium salt (a final reaction product of N-acetylglucosamine labeling by (2-aminoethyl)trimethylammonium salt) between acetonitrile-rich and water-rich layers was monitored by hydrophilic interaction chromatography with electrospray ionization mass spectrometry. Despite the poor solubility of both highly polar substances in solutions containing a high concentration of acetonitrile, the main portion of the labeling reagent (72%) can be removed from the crude reaction mixture in the first extraction step using 95% acetonitrile/5% water as an extraction solvent. The purified final reaction product contained only 2% of the labeling reagent, and it was suitable for analysis by direct infusion mass spectrometry to confirm its identity. The capability of the suggested purification protocol to process small-volume highly salted reaction mixtures was also proven by analysis of saccharide mixture containing glucose, maltose, and maltotriose labeled by the positively charged tag.

Palladium-catalyzed alkynylation of aromatic amines via in situ formed trimethylammonium salts

A palladium-catalyzed alkynylation of aromatic amines with terminal alkynes via in situ formed trimethylammonium salts is developed. Compared with previous system using ammonium salts as starting materials and high loading of pre-prepared NHC-Pd catalyst (10 mol% Pd), this reaction directly employed amines as the coupling partners and the commercially available Pd2(dba)3/PPh2Cy (1 mol% Pd) as the catalyst, greatly simplifying the manipulation and decreasing the cost.

Transition metal-free coupling reactions of benzylic trimethylammonium salts with di(hetero)aryl disulfides and diselenides.

A new protocol was developed to synthesize (enantioenriched) thioethers and selenoethers from (chiral) benzylic trimethylammonium salts and di(hetero)aryl disulfides or diselenides. These syntheses were promoted by the presence of weak base and did not require the use of any transition metal, and resulted in the target products with good to excellent yields (72-94%). Using quaternary ammonium salts synthesized from enantiomerically enriched amines led to highly enantiopure benzylic thioethers and selenoethers (94-99% ee) with configurations reversed from those of their enantioenriched quaternary ammonium salts.