Singlet Fission in a New Series of Systematically Designed Through-space Coupled Tetracene Oligomers.

Singlet fission (SF) holds great promise for current photovoltaic technologies, where tetracenes, with their relatively high triplet energies, play a major role for application in silicon-based solar cells. However, the SF efficiencies in tetracene dimers are low due to the unfavorable energetics of their singlet and triplet energy levels. In the solid state, tetracene exhibits high yields of triplet formation through SF, raising great interest about the underlying mechanisms. To address this discrepancy, we designed and prepared a novel molecular system based on a hexaphenylbenzene core decorated with 2 to 6 tetracene chromophores. The spatial arrangement of tetracene units, induced by steric hindrance in the central part, dictates through-space coupling, making it a relevant model for solid-state chromophore organization. We then revealed a remarkable increase in SF quantum yield with the number of tetracenes, reaching quantitative (196 %) triplet pair formation in hexamer. We observed a short-lived correlated triplet pair and limited magnetic effects, indicating ineffective triplet dissociation in these through-space coupled systems. These findings emphasize the crucial role of the number of chromophores involved and the interchromophore arrangement for the SF efficiency. The insights gained from this study will aid designing more efficient and technology-compatible SF systems for applications in photovoltaics.

H-Bond Mediated Phase-Transfer Catalysis: Enantioselective Generating of Quaternary Stereogenic Centers in ß-Keto Esters.

In this work, we would like to present the development of a highly optimized method for generating the quaternary stereogenic centers in ß-keto esters. This enantioselective phase-transfer alkylation catalyzed by hybrid Cinchona catalysts allows for the efficient generation of the optically active products with excellent enantioselectivity, using only 1 mol% of the catalyst. The vast majority of phase-transfer catalysts in asymmetric synthesis work by creating ionic pairs with the nucleophile-attacking anionic substrate. Therefore, it is a sensible approach to search for new methodologies capable of introducing functional groups into the precursor's structure, maintaining high yields and enantiomeric purity.

Adjusting the Structure of ß-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs.

ß-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and association constants of the complexes formed, and the results revealed the unique properties of the chosen CDs as effective pH-dependent drug complexing agents. The association constants of the drug complexes with the CDs containing a triazole and lipoic acid (ßCDLip) or galactosamine (ßCDGAL), were significantly larger than that of the native ßCD. The AQ2CA and AQ2S drugs were poorly soluble, and their solubilities increased as a result of complex formation with ßCDLip and ßCDGAL ligands. AQ2CA and AQ2S are negatively charged at pH 7.4. Therefore, they were less prone to form an inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when protonated. The ßCDTriazole and ßCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at an acidic pH (pH 5.5) than in a neutral medium (pH 7.4) in which the drug dissociates to its neutral, uncharged form. This pH dependence is favorable for antitumor applications.

Stereoselective α-Chlorination of ß-Keto Esters in the Presence of Hybrid Amide-Based Cinchona Alkaloids as Catalysts.

We report an enantioselective phase transfer α-chlorination of ß-keto esters catalyzed by hybrid amide-based Cinchona derivatives. The chlorination process proceeds with proper quantitative yields (up to <99%) and high asymmetric induction (up to 97% ee). We show that the use of only 0.5 mol % hybrid catalyst based on a Cinchona core allows the chlorination reaction to be conducted in a highly enantioselective manner with various indanone and tetralone carboxylate esters.

Highly Enantioselective Epoxidation of α,ß-Unsaturated Ketones Using Amide-Based Cinchona Alkaloids as Hybrid Phase-Transfer Catalysts.

A series of 20 one chiral epoxides were obtained with excellent yields (up to 99%) and enantioselectivities (up to >99% ee) using hybrid amide-based Cinchona alkaloids. Our method is characterized by low catalyst loading (0.5 mol %) and short reaction times. Moreover, the epoxidation process can be carried out in 10 cycles, without further catalyst addition to the reaction mixture. This methodology significantly enhance the scale of the process using very low catalyst loading.

Water-soluble galactosamine derivative of ß-cyclodextrin as protective ligand and targeted carrier for delivery of toxic anthracycline drug.

ß-cyclodextrin modified with an electron-rich aromatic triazole linker and targeting moiety (galactosamine) was synthesized and studied as a carrier for the anticancer drug, doxorubicin (DOX), with the aim of targeting the pathological cells, reducing the cardiotoxic side effects and increasing the binding of the drug to DNA. The ß-cyclodextrins modified with galactosamine (ßCDGAL) are non-toxic and highly soluble in aqueous medium compared to the native ßCD and ßCD modified only with aromatic moiety, such as triazole linker. Molecular modelling and NMR study gave a deeper insight into the ligand structure, providing an explanation for its increased solubility, and the drug-ligand interactions. The triazole linker strengthened the drug binding and introduced pH dependence of the complex stability constants for ßCDGAL derivative, as confirmed by the voltammetry measurements. Spectroscopic studies have shown that entrapment of the DOX in ßCDGAL cavity reduces the stability constant of the DOX:Fe(III) complex responsible for the production of cardiotoxic reactive oxygen species and additionally supports the binding of the drug to the double strand DNA. The MTT assay and confocal microscopy results showed that despite encapsulation of the drug in the cyclodextrin molecule, its cytotoxic effect on the liver cancer cell line (HepG2) is comparable to that of the free, non-protected drug.

Selective Carboxylate Recognition Using Urea-Functionalized Unclosed Cryptands: Mild Synthesis and Complexation Studies.

Herein we present the synthesis and evaluation of anion-binding properties of 12 new receptors from the unclosed cryptand family. Their core is built on the stable 26-membered tetraamidic macrocyclic scaffold, whereas various alkyl and aryl urea substituents were introduced after a yield-limiting macrocyclization step (65-98%). The receptors strongly bind anions, in particular carboxylates, even in a highly competitive solvent mixture (DMSO-d6 + H2O 95:5 v/v).

Amide-Based Cinchona Alkaloids as Phase-Transfer Catalysts: Synthesis and Potential Application.

Herein we present a library of simple amide derivatives of Cinchona alkaloids in the form of quaternary ammonium salts. The obtained derivatives can be generated very easily and efficiently from inexpensive and commercially available substrates. We tested this class of alkaloids in the alkylation of glycine derivative, carried out under phase-transfer catalyst conditions. The presented hybrid catalysts offer both high reaction yields (up to 97%) and high enantioselectivities of the obtained product (up to 94% ee).

Competition between self-inclusion and drug binding explains the pH dependence of the cyclodextrin drug carrier - molecular modelling and electrochemistry studies.

A non-toxic lipoic acid derivative of ß cyclodextrin (ßCDLip) with an electron-rich aromatic linker was studied as a carrier for the drug doxorubicin with the aim of decreasing the toxic side effects of this drug. The modified cyclodextrin strengthened the drug binding and differentiated the complex-forming ability with dependence on pH. The stability constants of the complexes were evaluated by voltammetry and spectrofluorometry. Molecular modelling provided deeper insight into the nature of the ligand structure itself and the drug-ligand interactions, showing the different contributions of the self-inclusion of the ligand substituent at different pH values. As a result, the modes of interaction of ßCDLip with the drug and factors affecting the stabilities of the complex under the pH conditions of healthy and tumour cells could be discovered and explained.

A General Method for Synthesis of Unclosed Cryptands via H-Bond Templated Macrocyclization and Subsequent Mild Postfunctionalization.

A practical four-step synthesis of a model 26-membered N-Boc-protected macrocycle, starting from commercially available and inexpensive materials, is reported. The crucial macrocyclization step does not require high-dilution conditions and is completed in a short time (8 h). The high yield of macrocyclization (61%) is achieved owing to templation by intramolecular H-bonds and a chloride anion, which both help to adopt a favorable folded conformation of the open-chain intermediate. Finally, mild, selective, and efficient incorporation of intraannular amide function leading to five diversely functionalized unclosed cryptands (UCs) is described.