Investigation of Weak Noncovalent Interactions Directed by the Amino Substituent of Pyrido- and Pyrimido-[1,2-a]benzimidazole-8,9-diones.

Quinones are small redox-active molecules that are able to form intra- and intermolecular interactions both in the solid state and in solution. On the basis of 6-amino-substituted pyrido- and pyrimido-[1,2-a]benzimidazole-8,9-diones, weak interactions were investigated by single-crystal X-ray and 1H NMR spectroscopy methods. Crystallization of quinone derivatives containing a -NH-CH2- fragment led to the formation of both chiral and achiral crystals. The presence of two forms with (endo form) and without (exo form) an intramolecular hydrogen bond was experimentally detected by X-ray crystallography analysis and variable-temperature (VT) 1H NMR experiments in the cases of isopentylamino- and benzylamino-substituted derivatives. Interestingly, the exo form dominates both in the solid state and in solution.

Thiazoline Carbene-Cu(I)-Amide complexes: Efficient White Electroluminescence from Combined Monomer and Excimer Emission.

Luminescent carbene-metal-amide complexes bearing group 11 metals (Cu, Ag, Au) have recently attracted great attention due to their exceptional emission efficiency and high radiative decay rates (kr). These materials provide a less costly alternative to organic light-emitting diode (OLED) emitters based on more scarce metals, such as Ir and Pt. Herein, a series of eight Cu(I) complexes bearing as yet unexplored 1,3-thiazoline carbenes have been investigated and analyzed with respect to their light emission properties and OLED application. For the first time among the class of copper-based organometallic compounds the formation of efficient electroluminescent excimers is demonstrated. The prevalence of electroluminescence (EL) from either the monomer (bluish green) or the excimer (orange-red) can be adjusted in vacuum-deposited emissive layers by altering the extent of steric encumbrance of the emitter or its concentration. Optimized conditions in terms of the emitter structure and mass fraction allowed a simultaneous EL from the monomer and excimer, which laid the basis for a preparation of a single-emitter white OLED (WOLED) with external quantum efficiency of 16.5% and a maximum luminance of over 40000 cd m-2. Wide overlapping emission bands of the monomer and excimer ensure a device color rendering index (CRI) of above 80. In such a way the prospects of copper complexes as cost-effective materials for lighting devices are demonstrated, offering expense reduction through a cheaper emissive component and a simplified device architecture.

Synthesis of Asymmetric Coupled Polymethines Based on a 7-Chloropyrido[1,2-a]benzimidazole-8,9-dione Core.

A synthesis of 7-chloropyrido[1,2-a]benzimidazole-8,9-dione derivatives bearing fragments of widely used acceptor units has been performed, and their structures were investigated using the principle of coupled polymethines. Their electronic and electrochemical properties have also been studied. Compounds were isolated in both salt and neutral forms and depending on the introduced substituent can exist as o-quinone or p-quinone methide.

Carbene-Metal Complexes As Molecular Scaffolds for Construction of through-Space Thermally Activated Delayed Fluorescence Emitters.

The through-space charge transfer (CT) process is observed in Cu(I) carbene-metal-amide complexes, where conventional imidazole or imidazoline N-heterocyclic (NHC) carbene fragments act as inert linkers and CT proceeds between a metal-bound carbazole donor and a distantly situated carbene-bound phenylsulfonyl acceptor. The resulting electron transfer gives a rise to efficient thermally activated delayed fluorescence (TADF), characterized with high photoluminescence quantum yields (ΦPL up to 90%) and radiative rates (kr) up to 3.32 × 105 s-1. The TADF process is aided by fast reverse intersystem crossing (rISC) rates of up to 2.56 × 107 s-1. Such emitters can be considered as hybrids of two existing TADF emitter design strategies, combining low singlet-triplet energy gaps (ΔEST) met in all-organic exciplex-like emitters (0.0062-0.0075 eV) and small, but non-negligible spin-orbital coupling (SOC) provided by a Cu atom, like in TADF-active organometallic complexes.

The Specificity and Broad Multitarget Properties of Ligands for the Free Fatty Acid Receptors FFA3/GPR41 and FFA2/GPR43 and the Related Hydroxycarboxylic Acid Receptor HCA2/GPR109A.

The paradigm of ligand-receptor interactions postulated as "one compound-one target" has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity. Oxopyranopyrimidine and thioxopyranopyrimidine type compounds have been studied as ligands of the HCA2/GPR109A receptor; nevertheless, they exhibited equal or higher activity towards FFA3/GPR41 and FFA2/GPR43 receptors. S-Alkyl derivatives of pyranopyrimidines that have not yet been studied as ligands of GPCRs were more active towards HCA2/GPR109A and FFA3/GPR41 receptors than towards FFA2/GPR43. Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-α) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. This study revealed groups of compounds possessing multitarget activity towards several receptors. The obtained data could be useful for further development of multitarget ligands.

4-Pyridinio-1,4-Dihydropyridines as Calcium Ion Transport Modulators: Antagonist, Agonist, and Dual Action.

A set of six new 4-pyridinio-1,4-dihydropyridine (1,4-DHP) compounds has been synthesized. The calcium channel modulating activity of these compounds was evaluated in an aorta vascular smooth muscle cell line (A7R5), in an isolated rat aortic ring model, and in human neuroblastoma cell lines (SH-SY5Y). The antagonistic effect of these 1,4-DHP was tested by modulating the impact of carbachol-dependent mobilization of intracellular Ca2+ in SH-SY5Y cells. The intracellular free Ca2+ concentration was measured in confluent monolayers of SH-SY5Y cells and A7R5 cells with the Ca2+-sensitive fluorescent indicator Fluo-4 NW. Only four compounds showed calcium channel blocking activity in SH-SY5Y and A7R5 cells as well as in the aortic ring model. Among them, compound 3 was the most active calcium channel antagonist, which had 3 times higher activity on carbachol-activated SH-SY5Y cells than amlodipine. Two of the compounds were inactive. Compound 4 had 9 times higher calcium agonist activity than the classic DHP calcium agonist Bay K8644. The intracellular mechanism for the action of compound 4 using inhibitor analysis was elucidated. Nicotinic as well as muscarinic receptors were not involved. Sarcoplasmic reticulum (ER) Ca2+ (SERCA) stores were not affected. Ryanodine receptors (RyRs), another class of intracellular Ca2+ releasing channels, participated in the agonist response evoked by compound 4. The electrooxidation data suggest that the studied compounds could serve as antioxidants in OS.

Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds.

Three groups of synthetic lipids are chosen for studies: (1) 1,4-dihydropyridines (1,4-DHPs) containing two cationic moieties and their analogues; (2) 3,4-dihydro-2(1H)-pyridones containing a cationic moiety; and (3) acyclic, open-chain analogues, i.e., 2-amino-3-alkoxycarbonylalkylammonium derivatives. 1,4-DHPs possessing dodecyl alkyl chains in the ester groups in positions 3 and 5 and cationic nitrogen-containing groups in positions 2 and 6 have high cytotoxicity in cancer cells HT-1080 (human lung fibrosarcoma) and MH-22A (mouse hepatoma), but low cytotoxicity in the noncancerous NIH3T3 cells (mouse embryonic fibroblast). On the contrary, similar compounds having short (methyl, ethyl, or propoxyethyl) chains in the ester groups in positions 3 and 5 lack cytotoxicity in the cancer cells HT-1080 and MH-22A even at high doses. Inclusion of fluorine atoms in the alkyl chains in positions 3 and 5 of the DHP cycle decreases the cytotoxicity of the mentioned compounds. Structurally related dihydropyridones with a polar head group are substantially more toxic to normal and cancerous cells than the DHP analogues. Open-chain analogues of DHP lipids comprise the same conjugated aminovinylcarbonyl moiety and possess anticancer activity, but they also have high basal cytotoxicity. Electrochemical oxidation data demonstrate that oxidation potentials of selected compounds are in the range of 1.6-1.7 V for cationic 1,4-DHP, 2.0-2.4 V for cationic 3,4-dihydropyridones, and 1.2-1.5 V for 2-amino-3-alkoxycarbonylalkylammonium derivatives. Furthermore, the tested cationic 1,4-DHP amphiphiles possess antiradical activity. Molecular topological polar surface area values for the tested compounds were defined in accordance with the main fragments of compound structures. The determined logP values were highest for dodecyl ester groups in positions 3 and 5 of the 1,4-DHP and lowest for short alkyl chain-containing amphiphiles.

Natural-Antioxidant-Inspired Benzo[b]selenophenes: Synthesis, Redox Properties, and Antiproliferative Activity.

The cyclization of arylalkynes under selenobromination conditions, combined with an acid-induced 3,2-aryl shift, was elaborated as a general synthetic pathway for the preparation of polyhydroxy-2- and -3-arylbenzo[b]selenophenes from the same starting materials. The redox properties, free-radical-scavenging ability, and cytotoxicity against malignant cell lines (MCF-7, MDA-MB-231, HepG2, and 4T1) of the synthesized compounds were explored, and the obtained results were used to consider the structure-activity relationships (SARs) in these compounds. Consequently, the structural features that were responsible for the highly potent peroxyl-radical-scavenging activity were established.

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions.

Stable heterocyclic hydroperoxide can be easily prepared as a product of fast oxidation of a 1,2,3,4-tetrahydropyridine by (3)O2 if the solution is exposed to sunlight. The driving force for the photoinduced electron transfer is calculated from electrochemical and spectroscopic data. The outcome of the reaction depends on the light intensity and the concentration of O2. In the solid state the heterocyclic hydroperoxide is stable; in solution it is involved in further reactions.