Effects of Electron-Withdrawing Strengths of the Substituents on the Properties of 4-(Carbazolyl-R-benzoyl)-5-CF3-1H-1,2,3-triazole Derivatives as Blue Emitters for Doping-Free Electroluminescence Devices.

The synthesis of four 4-(carbazolyl-R-benzoyl)-5-CF3-1H-1,2,3-triazoles with extra groups ((3-methyl)-phenyl-, 4-fluorophenyl-, quinolinyl-, or (3-trifluoromethyl)-phenyl-) in the acceptor fragment has been reported. The effects of substituents with different electron-withdrawing strengths on the thermal, electrochemical, photophysical, and electroluminescence properties of the synthesized compounds are discussed. The results of X-ray analyses and density functional theory (DFT) calculations support unusual molecular packing and electronic properties. The compounds are capable of glass formation with glass transition temperatures ranging from 54-84 °C. Ionization potentials of the compounds are in the range of 5.98-6.22 eV and electron affinities range from 3.09 to 3.35 eV. Under ultraviolet excitation, the neat films of the compounds exhibit blue emission with photoluminescence quantum yields ranging from 18 to 27%. The films of selected compounds are used for the preparation of host-free light-emitting layers of organic light-emitting diodes with very simple device structures and an external quantum efficiency of 4.6%.

Bioisosteric replacement of 1H-1,2,3-triazole with 1H-tetrazole ring enhances anti-leukemic activity of (5-benzylthiazol-2-yl)benzamides.

Previously, we discovered that N-(5-benzyl-1,3-thiazol-2-yl)-4-(5-methyl-1H-1,2,3-triazol-1-yl)benzamide possessed a remarkable cytotoxic effect on 28 cancer cell lines with IC50 < 50 µM, including 9 cancer cell lines, where IC50 was in the range of 2.02-4.70 µM. In the present study, we designed a novel N-(5-benzylthiazol-2-yl)amide compound 3d that was synthesized using the original bioisosteric replacement of 1H-1,2,3-triazole ring by the 1H-tetrazole ring. A significantly enhanced anticancer activity in vitro with an excellent anti-leukemic potency towards chronic myeloid leukemia cells of the K-562 line was demonstrated. Two compounds - 3d and 3l - were highly cytotoxic at nanomolar concentrations towards various tumor cells of the following lines: K-562, NCI-H460, HCT-15, KM12, SW-620, LOX IMVI, M14, UACC-62, CAKI-1, and T47D. As a highlight, the compound N-(5-(4-fluorobenzyl)thiazol-2-yl)-4-(1H-tetrazol-1-yl)benzamide 3d inhibited the growth of leukemia K-562 cells and melanoma UACC-62 cells with IС50 of 56.4 and 56.9 nM (SRB test), respectively. The viability of leukemia K-562 and pseudo-normal HaCaT, NIH-3T3, and J774.2 cells was measured by the MTT assay. Together with SAR analysis, it allowed the selection of a lead compound 3d, which demonstrated the highest selectivity (SI = 101.0) towards treated leukemic cells. The compound 3d caused DNA damage (single-strand breaks detected by the alkaline comet assay) in the leukemic K-562 cells. The morphological study of the K-562 cells treated with compound 3d revealed changes consistent with apoptosis. Thus, the bioisosteric replacement in (5-benzylthiazol-2-yl)amide scaffold proved to be a perspective approach in the design of novel heterocyclic compounds with enhanced anticancer potential.

Novel N-(4-thiocyanatophenyl)-1H-1,2,3-triazole-4-carboxamides exhibit selective cytotoxic activity at nanomolar doses towards human leukemic T-cells.

The N-(4-thiocyanatophenyl)-1H-1,2,3-triazole-4-carboxamides were synthesized via the condensation of variety of 1H-1,2,3-triazole-4-carboxylic acids and 4-thiocyanatoaniline using CDI as amide coupling reagents. According to computer-aided calculations, all synthesized compounds are expected to have acceptable ADME profile for drug design. The antiproliferative potency of derivatives was evaluated towards different cell lines. The specific activity of four N-(4-thiocyanatophenyl)-1H-1,2,3-triazole-4-carboxamides (4a, 4b, 4c, 4f) was comparable to doxorubicin (GI50 = 0.65 µM) at nanomolar level against Jurkat cells in the range of GI50 0.63-0.69 µM. According to the results of toxicity studies of the compounds for HEK293, HaCaT, Balb/c 3T3 cells, compound 4a was selected for further studies as a biocompatible agent with promising anticancer activity in the NCI60 cell lines. A remarkable antiproliferative activity of compound 4a towards leukemia cell lines (SR, MOLT-4; CCRF-CEM; HL-60(TB); K-562; RPMI-8226) was observed and high cytotoxicity towards the CAKI-1 (kidney cancer), LOX IMVI (melanoma) and UO-31 (renal cancer) cells lines was detected. Compound 4a inhibits LOX IMVI cells growth at a GI50 value of 0.15 µM. COMPARE analysis to indicate potential mechanisms of action of novel compound, as well as in silico SwissTargetPrediction and SwissSimilarity were performed. Compound 4a induced morphological changes (apoptotic bodies, membrane blebbing, chromatin condensation), and DNA fragmentation in Jurkat T-cells. It reduced mitochondrial membrane potential and induced DNA damage in Jurkat cells without binding and/or intercalation to DNA molecule.

Exciplex-Forming Systems of Physically Mixed and Covalently Bonded Benzoyl-1H-1,2,3-Triazole and Carbazole Moieties for Solution-Processed White OLEDs.

Using the newly designed exciplex-forming 1,2,3-triazole-based acceptors with fast and efficient singlet → triplet intersystem crossing (ISC) processes, carbazole and benzoyl-1H-1,2,3-triazole derivatives were synthesized by Dimroth-type 1,2,3-triazole ring formation and Ullmann-Goldberg C-N coupling reactions. Due to the exciplex formation between covalently bonded electron-donating (carbazole) and 1,2,3-triazole-based electron-accepting moieties with small singlet-triplet splitting (0.07-0.13 eV), the compounds exhibited ISC-assisted bluish-green thermally activated delayed fluorescence. The compounds were characterized by high triplet energy levels ranging from 2.93 to 2.98 eV. The most efficient exciplex-type thermally activated delayed fluorescence was observed for ortho-substituted carbazole-benzoyl-1H-1,2,3-triazole which was selected as a host in the structure of efficient solution-processed white light-emitting diodes. The best device exhibited a maximum power efficiency of 10.7 lm/W, current efficiency of 18.4 cd/A, and quantum efficiency of 7.1%. This device also showed the highest brightness exceeding 10 thousand cd/m2. Usage of the exciplex-forming host allowed us to achieve a low turn-on voltage of 3.6 V. High-quality white electroluminescence was obtained with the close to nature white color coordinates (0.31, 0.34) and a color rendering index of 92.

Synthesis, crystal structure and Hirshfeld surface analysis of (4-methyl-phen-yl)[1-(penta-fluoro-phen-yl)-5-(tri-fluoro-meth-yl)-1H-1,2,3-triazol-4-yl]methanone.

The title compound, C17H7F8N3O, was obtained via the reaction of 1-azido-2,3,4,5,6-penta-fluoro-benzene with 4,4,4-tri-fluoro-1-(p-tol-yl)butane-1,3-dione using tri-ethyl-amine as a base catalyst and solvent. The dihedral angles between the penta-fluoro-phenyl (A), triazole (B) and p-tolyl (C) rings are A/B = 62.3 (2), B/C = 43.9 (3) and A/C = 19.1 (3)°. In the crystal, the mol-ecules are linked by C-H⋯F and C-H⋯O hydrogen bonds as well as by aromatic π-π stacking inter-actions into a three-dimensional network. To further analyse the inter-molecular inter-actions, a Hirshfeld surface analysis was performed.

Syntheses and crystal structures of two copper(I)-halide π,σ-coordination compounds based on 2-[(prop-2-en-1-yl)sulfan-yl]pyridine.

The title compounds, di-µ-chlorido-bis-({2-[(η-2,3)-(prop-2-en-1-yl)sulfan-yl]pyridine-κN}copper(I)), [Cu2Cl2(C8H9NS)2], and di-µ-bromido-bis-({2-[(η-2,3)-(prop-2-en-1-yl)sulfan-yl]pyridine-κN}copper(I)), [Cu2Br2(C8H9NS)2], were obtained by alternating-current electrochemical synthesis starting from an ethano-lic solution of 2-[(prop-2-en-1-yl)sulfan-yl]pyridine (Psup) and the copper(II) halide. The isostructural crystals are built up from centrosymmetric [Cu2 Hal 2(Psup)2] dimers, which are formed due to the π,σ-chelating behavior of the organic ligand. In the crystals, the dimers are linked by C-H⋯Hal hydrogen bonds as well as by aromatic π-π stacking inter-actions into a three-dimensional network.

Synthesis, crystal structure and Hirshfeld surface analysis of 5-cyclo-propyl-N-(2-hy-droxy-eth-yl)-1-(4-methyl-phen-yl)-1H-1,2,3-triazole-4-carboxamide.

The title compound, C15H18N4O2, was obtained via a two-step synthesis (Dimroth reaction and amidation) for anti-cancer activity screening and was selected from a 1H-1,2,3-triazole-4-carboxamide library. The cyclo-propyl ring is oriented almost perpendicular to the benzene ring [dihedral angle = 87.9 (1)°], while the dihedral angle between the mean plane of the cyclo-propyl ring and that of the triazole ring is 55.6 (1)°. In the crystal, the mol-ecules are linked by O-H⋯O and C-H⋯N inter-actions into infinite ribbons propagating in the [001] direction, which are inter-connected by weak C-H⋯O inter-actions into layers. The inter-molecular inter-actions were characterized via Hirshfeld surface analysis, which indicated that the largest fingerprint contact percentages are H⋯H (55.5%), N⋯H/H⋯N (15.4%), C⋯H/H⋯C (13.2%) and O⋯H/H⋯O (12.9%).

Synthesis, crystal structure and Hirshfeld surface analysis of N-(4-chloro-phen-yl)-5-cyclo-propyl-1-(4-meth-oxy-phen-yl)-1H-1,2,3-triazole-4-carboxamide.

The title compound, C19H17ClN4O2, was obtained via a two-step synthesis involving the enol-mediated click Dimroth reaction of 4-azido-anisole with methyl 3-cyclo-propyl-3-oxo-propano-ate leading to the 5-cyclo-propyl-1-(4-meth-oxy-phen-yl)-1H-1,2,3-triazole-4-carb-oxy-lic acid and subsequent acid amidation with 4-chloro-aniline by 1,1'-carbonyl-diimidazole (CDI). It crystallizes in space group P21/n, with one mol-ecule in the asymmetric unit. In the extended structure, two mol-ecules arranged in a near coplanar fashion relative to the triazole ring planes are inter-connected by N-H⋯N and C-H⋯N hydrogen bonds into a homodimer. The formation of dimers is a consequence of the above inter-action and the edge-to-face stacking of aromatic rings, which are turned by 58.0 (3)° relative to each other. The dimers are linked by C-H⋯O inter-actions into ribbons. DFT calculations demonstrate that the frontier mol-ecular orbitals are well separated in energy and the HOMO is largely localized on the 4-chloro-phenyl amide motif while the LUMO is associated with aryl-triazole grouping. A Hirshfeld surface analysis was performed to further analyse the inter-molecular inter-actions.

Nitrileimines as an alternative to azides in base-mediated click [3 + 2] cycloaddition with methylene active nitriles.

Nitrileimines were implemented in practical click protocols with oxopropanenitriles for the straightforward 5-amino-1H-pyrazole synthesis via 1,3-dipolar cycloaddition. The reaction proceeds at room temperature in a short time with base catalysis and no chromatographic purification. High purity products were isolated by simple filtration. The selectivity of the reaction was observed.

Crystal structure, Hirshfeld surface analysis and computational studies of 5-[(prop-2-en-1-yl)sulfan-yl]-1-[2-(tri-fluoro-meth-yl)phen-yl]-1H-tetra-zole.

The title compound, C11H9F3N4S, was synthesized from 2-(tri-fluoro-meth-yl)aniline by a multi-step reaction. It crystallizes in the non-centrosymmetric space group Pna21, with one mol-ecule in the asymmetric unit, and is constructed from a pair of aromatic rings [2-(tri-fluoro-meth-yl)phenyl and tetra-zole], which are twisted by 76.8 (1)° relative to each other because of significant steric hindrance of the tri-fluoro-methyl group at the ortho position of the benzene ring. In the crystal, very weak C-H⋯N and C-H⋯F hydrogen bonds and aromatic π-π stacking inter-actions link the mol-ecules into a three-dimensional network. To further analyse the inter-molecular inter-actions, a Hirshfeld surface analysis, as well as inter-action energy calculations, were performed.

Anticancer Activity Evaluation of New Thieno[2,3-d]pyrimidin-4(3H)-ones and Thieno[3,2-d]pyrimidin-4(3H)-one Derivatives.

Anticancer screening of several novel thienopyrimidines has been performed. The thienopyrimidine derivatives were synthesized from available starting materials according to the convenient synthetic procedures using a one-pot solvent-free reaction which gave a wide access to thienopyrimidine-derivative production. The synthesized compounds were preselected via molecular docking to be tested for their anticancer activity in NCI 60 cell lines. It was observed that some compounds showed remarkable anticancer activity. It was found that the most active compound among thieno[2,3-d]pyrimidine-4(3H)-ones is 2-(benzylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one, which possesses cytotoxic activity on almost all cancer cell lines with mean growth 51.01%, where the most sensitive was the melanoma cell line MDA-MB-435 with GP (Growth Percent) = -31.02%. The patterns of structure⁻activity that are important for further optimization of the structure and the creation of more selective and active anticancer agents were proposed.

Two Related Copper(I) π-Complexes Based on 2-Allyl-5-(2-pyridyl)-2H-tetrazole Ligand: Synthesis and Structure of [Cu(2-apyt)NO3] and [Cu(2-apyt)(H2O)](BF4) Compounds.

By means of the alternating current electrochemical technique two new π-compounds [Cu(2-apyt)NO3] (1) and [Cu(2-apyt)(H2O)](BF4) (2) have been obtained starting from the mixture of 1-allyl-5-(2-pyridyl)-2H-tetrazole (1-apyt), 2-allyl-5-(2-pyridyl)-2H-tetrazole (2-apyt) and corresponding copper(II) salts, and have been structurally studied. Selective complexation towards 2-allyl- isomer results in a formation of 2-apyt complexes. Copper(I) ion in both 1 and 2 complexes coordinates the allylic C=C bond, one pyridyl and one tetrazole N atoms. In both structures Cu+ center adopts distorted tetrahedral surrounding which additionally includes oxygen of NO3(-) in 1 and H2O moiety in 2. Structure 1 is built from [Cu(2-apyt)NO3]2 dimeric fragments. Contrary, participation of H2O in the metal coordination in 2 leads to the infinite {[Cu(2-apyt)(H2O)]+}n chain construction. To analyze interactions between the particles in 1 and 2 Hirshfeld surface analysis was performed.

New Convenient Strategy for Annulation of Pyrimidines to Thiophenes or Furans via the One-pot Multistep Cascade Reaction of 1H-Tetrazoles with Aliphatic Amines.

A versatile, convenient, efficient and high-yield synthetic method for 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[2,3-d]pyrimidin-4(3H)-ones, 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[3,2-d]pyrimidin-4(3H)-ones, and benzofuro[3,2-d]pyrimidin-4(3H)-ones preparation has been developed. The reaction proceeded without using solvents and included several steps. A variety of thieno[2,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives with substituents of different nature were obtained in high yields from substituted alkyl 2-(1H-tetrazol-1-yl)thiophene-3-carboxylates, 3-(1H-tetrazol-1-yl)thiophene-2-carboxylates, and 3-(1H-tetrazol-1-yl)benzofuran-2-carboxylate after their treatment with aliphatic amines.

Synthesis of 1,2,3-Triazole Derivatives and Evaluation of their Anticancer Activity.

Anticancer screening of several 1,2,3-triazoles with heterocyclic fragments has been performed. The 1,2,3-triazole derivatives were synthesized from available starting materials according to convenient synthetic procedures. The antitumor activity of the synthesized compounds was tested in vitro by the National Cancer Institute in NCI60 cell lines. It was observed that some compounds showed slight anticancer activity. One of them possessed a moderate activity against melanoma, colon, and breast cancer. Standard COMPARE analysis was performed at the GI50 level.

First Silver(I) - Complexes with Tetrazole Allyl Derivatives. Synthesis and Crystal Structure of [Ag2(C10H10N4S)2(H2O)2](BF4)2 and [Ag(C10H9ClN4S)(NO3)] π-Compounds (C10H10N4S and C10H9ClN4S - 5-(Allylthio)-1-phenyl- and 5-(Allylthio)-1-(4-chlorophenyl)-1H-tetrazole).

Crystalline silver(I) π complexes [Ag2(atpt)2(H2O)2](BF4)2 (1) (atpt - 5-(allylthio)-1-phenyl-1H-tetrazole (C10H10N4S)) and [Ag(atcpt)(NO3)] (2) (atcpt - 5-(allylthio)-1-(4-chlorophenyl)-1H-tetrazole (C10H9ClN4S)) complexes have been obtained using silver salt and the organic ligands. Compounds were characterized by X-ray single crystal diffraction: for 1 space group P21/n, a = 10.4560(5), b = 11.4008(5), c = 12.7550(7) Å, ß = 98.128(3)°, V = 1505.21(13) Å3 at 200 K, Z = 2; for 2: space group P21/a, a = 8.6790(8), b = 13.7324(10), c = 12.4597(13) Å, ß = 102.288(5)°, V = 1451.0(2) Å3 at 200 K, Z = 4. In both structures silver(I) atoms possess a trigonal pyramidal coordination environment with essentially different coordination modes of organic ligands. The Ag(I) arrangement in 1 involves the N3 and N4 atoms of two adjacent atpt molecules, an olefin C=C bond and a water molecule at the apical position. In crystal structure of 2 two O atoms from NO3- anions occupy two equatorial position of silver(I) coordination polyhedron, and atcpt is attached to the metal centre through the N4 atom of tetrazole core only. The weakly bound C=C bond is located at the apical position of Ag(I) environment.

One-pot multicomponent synthesis of 1-aryl-5-methyl-N-R2-1H-1,2,3-triazole-4-carboxamides: an easy procedure for combinatorial chemistry.

A convenient synthetic protocol was elaborated for creation of combinatorial libraries of 1-(R(1)-phenyl)-5-methyl-N-R(2)-1H-1,2,3-triazole-4-carboxamides. As starting materials, commercially available or readily prepared azides, amines, and diketene were selected for the reaction which has proceeded in a one-pot system with high yields and in short time.