Synthesis and Characterization of Un-doped Deep-Blue Organic Light-Emitting Materials Containing Spirofluorene and Biphenyl or Substituted Biphenyl

A series of novel blue light-emitting materials, spirofluorene derivatives, DBSF, 3DBSF, and 5DBSF, based on 2′,7′-dibromospiro- [benzo[c]fluorene-7,9′-fluorene] (DBrSPFF) were successfully synthesized and identified by IR, ¹H-NMR, and¹³C-NMR, MS. Optical properties were examined by UV-Vis absorption spectra and photoluminescence (PL) emission spectra. They performed great blue light characteristics. PL quantum yield was calculated by using quinine sulphate in 0.1M H₂SO₄ as standard. Electro-chemical behavior was examined through cyclic voltammeter measurement. They may be potential promising blue light-emitting materials for OLED.     

Synthesis and Characterization of Telmisartan-Derived Cell Death Modulators to Circumvent Imatinib Resistance in Chronic Myeloid Leukemia

New strategies to eradicate cancer stem cells in chronic myeloid leukemia (CML) include a combination of imatinib with peroxisome proliferator-activated receptor gamma (PPARγ) ligands. Recently, we identified the partial PPARγ agonist telmisartan as effective sensitizer of resistant K562 CML cells to imatinib treatment. Here, the importance of the heterocyclic core on the cell death-modulating effects of the telmisartan-derived lead 4′-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid ( 3 b ) was investigated. Inspired by the pharmacodynamics of HYL-6d and the selective PPARγ ligand VSP-51, the benzimidazole was replaced by a carbazole or an indole core. The results indicate no correlation between PPARγ activation and sensitization of resistant CML cells to imatinib. The 2-COOH derivatives of the carbazoles or indoles achieved low activity at PPARγ, while the benzimidazoles showed 60-100 % activation. Among the 2-CO₂CH₃ derivatives, only the ester of the lead ( 2 b ) slightly activated PPARγ. Sensitizing effects were further observed for this non-cytotoxic 2 b (80 % cell death), and to a lesser extent for the lead 3 b or the 5-Br-substituted ester of the benzimidazoles ( 5 b ).     

Synthesis and characterization of Cu(I) and Zn(II) complexes with new sulfur-bearing isoxazole- or pyrazole-based ligands

The synthesis of the new ligands 6-(5-methyl-1,2-oxazol-3-yl)-2,3-dihydro-5H-[1,4] dithiino[2,3-c]pyrrole-5,7(6H)-dione (isox′) and 6-(3-methyl-1H-pyrazol-5-yl)-2,3-dihydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione (pyraz′) and their coordination chemistry toward Cu(I) and Zn(II), was studied. The ligands and their complexes were characterized using a combination of either multinuclear NMR (¹H and ¹³C{¹H}), HRMS, FTIR or Uv–Vis spectroscopy. The solid state structures of ligand isox′ and complexes [Cu(pyraz′)₂]OTf and [Zn(OOCCF₃)₂(pyraz′)₂] were determined. Interestingly, isox′ presents a yellow luminescence in its free form. Additionally, the ability of isox′ to coordinate as an N–O bidentate ligand or as an N–S bridge between two copper centers, forming a coordination polymer, is studied. The solid state structure of this Cu(I)-isox′ 1D coordination polymer is also reported.     

Synthesis and Preliminary Evaluation of 11C-Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4

Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M₁–M₅) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M₁/M₄-preferring agonist, in patients of schizophrenia and Alzheimer's disease, M₁- or M₄-selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of ¹¹C-labeled positron emission tomography (PET) ligands based on a validated M₄R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [¹¹C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay-corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq μmol⁻¹). In vitro autoradiography studies indicated that these three ligands possess moderate-to-high in vitro specific binding to M₄R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability.     

Novel,Dual Target-Directed Annelated Xanthine Derivatives Acting on Adenosine Receptors and Monoamine Oxidase B

Annelated purinedione derivatives have been shown to act as possible multiple-target ligands, addressing adenosine receptors and monoaminooxidases. In this study, based on our previous results, novel annelated pyrimido- and diazepino[2,1-f]purinedione derivatives were designed as dual-target-directed ligands combining A_2A adenosine receptor (AR) antagonistic activity with blocking monoamine oxidase B. A library of 19 novel compounds was synthesized and biologically evaluated in radioligand binding studies at AR subtypes and for their ability to inhibit MAO-B. This allowed 9-(2-chloro-6-fluorobenzyl)-3-ethyl-1-methyl-6,7,8,9-tetrahydropyrimido[2,1-f]purine-2,4(1H,3H)-dione ( 13 e ; K_i human A_2AAR: 264 nM and IC₅₀ human MAO-B: 243 nM) to be identified as the most potent dual-acting ligand from this series. ADMET parameters were estimated in vitro, and analysis of the structure-activity relationships was complemented by molecular-docking studies based on previously published X-ray structures of the protein targets. Such dual-acting ligands, by selectively blocking A_2A AR, accompanied by the inhibition of dopamine metabolizing enzyme MAO-B, might provide symptomatic and neuroprotective effects in, among others, the treatment of Parkinson disease     

Spiroheterocyclic system. Part IV: Novel azo dye sulpha drugs of spiroheterocyclic naphthenes

Novel azo-dyes have been synthesized by diazotization of 4-amino benzene-4′-(substituted heterocyclo) sulphonamide derivatives and coupling with 1-oxa-4-thia-spiro[4,4]nonan-2-one (I) and/or with l-oxa-4-thia-spiro[4,5]decan-2-one (I′) in acid medium to give the corresponding 3-azo-(4′-substituted benzenesulphonamido)-l-oxa-4-thia-spiro[4,4]nonan-2-one (II-IX) and/or l-oxa-4-thia-spiro[4,5]decan-2-one (II′-IX′] as spiro-ligands. Treatment of these ligands with metal salts of iron (Fe³⁺), copper (Cu²⁺) and mercury (Hg²⁺) as chlorides in ethanolic solution furnished the corresponding metal chelates (II_a-c-IX_a-c) and/or (II′_a-c-IX′_a-c). The compounds were tested in vitro for antimicrobial activity to study the structure-activity relationship.     

Two New Zn(II) Coordination Polymers Constructed from Asymmetric Biphenyl-Dicarboxylate and Imidazole-Containing Ligands: Structures and Photoluminescent Properties

Two new coordination polymers, [Zn(2,4′-bpdc) (L₁)_0.5·(H₂O)] _n (1) and {[Zn(3,4′-bpdc) (L₁)]·(H₂O)} _n (2), have been obtained from hydrothermal reactions of zinc (II) nitrate with the ligands 1,4-bis(imidazol-1-yl)benzene (L) and two asymmetric biphenyl-dicarboxylate [biphenyl-2,4′-dicarboxylate (2,4′-bpdc) and biphenyl-3,4′-dicarboxylate (3,4′-bpdc)]. Single-crystal X-ray diffraction analysis the two coordination polymer show different structures due to the different dicarboxylate ligands. Complex 1 features a 3D mab topological net. Complex 2 is unusual case that has 3D frameworks constructed from 2D 4⁴-sql layers by parallel polycatenation. The photoluminescent properties of 1 and 2 have also been investigated.     

Light-Switchable Antagonists for the Histamine H1 Receptor at the Isolated Guinea Pig Ileum

The histamine H₁ G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H₁ receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H₁ ligands may contribute to a better mechanistic understanding and the development of improved correlations between ligand structure and pharmacologic effects. We report photochromic H₁ receptor ligands, which were investigated in an organ-pharmacological assay. Initially, five photochromic azobenzene derivatives of reported dual H₁–H₄ receptor antagonists were designed, synthesized, photochemically characterized, and organ-pharmacologically tested on the isolated guinea pig ileum. Among them, one compound [trans- 19 : (Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-phenyldiazenyl)phenyl)methanimine] retained the antagonistic activity of its non-photochromic lead, and trans–cis isomerization by irradiation induced a fourfold difference in the pharmacological response. Further structural optimization resulted in two bathochromically shifted derivatives of 19 [NO₂-substituted 35 {(Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-(4-nitrophenyl)diazenyl)phenyl)methanimine} and SO₃⁻-substituted 41 {4-((E)-(4-(((Z)-(4-chlorophenyl)(4-methylpiperazin-1-yl)methylene)amino)phenyl)diazenyl)benzenesulfonate}], which do not require the use of UV light for photoisomerization and which also have improved solubility and show reduced tissue impairment. The trans isomers of both compounds showed a remarkable increase in antagonistic activity relative to their lead trans- 19 ; furthermore, a 46-fold difference in activity on the isolated guinea pig ileum was observed between trans- and cis- 35 .     

Zinc(II)-Coordination Polymers Based on Isomeric Azo-Containing Anionic and Neutral Linkers

Four mixed-ligand coordination polymers, namely, [Zn(μ-3,3′-Cl₂abdc)(μ-4,4′-azobpy)]_n (1), [Zn(μ-4,4′-Cl₂abdc)(μ-3,3′-azobpy)_0.5(H₂O)]_n (2), [Zn₂(μ-4,4′-Cl₂abdc)(μ₄-4,4′-Cl₂abdc)_0.5(μ-OH)(μ-4,4′-azobpy)]_n (3) and {[Zn(H₂O)₄(μ-4,4′-azobpy)](4,4’-Cl₂abdc)}_n (4) (Cl₂abdc: dichloroazobenzenedicarboxylate and azobpy: azobispyridine) were synthesized with azo-group containing positional isomer anionic and neutral ligands in the presence of Zn(II) ion and characterized by elemental analysis, IR spectroscopy, single-crystal X-ray diffraction. X-ray results showed that the compounds displayed structural diversity depending on disposition of donor groups on ligands and solvent. Compounds 1 and 2 exhibited two-fold and five-fold interpenetrated 2D?→?2D structures, respectively, with the interchanging of positional isomer anionic and neutral ligands. Five-fold polycatenated 2D?→?3D structure was observed with the selection of 4,4′-Cl₂abdc and 4,4′-azobpy in 3. Although same ligands were used in the synthesis of 4 like compound 3, 1D structure of 4 was obtained with the use of DMF:water mixture and zinc nitrate. 4,4′-Cl₂abdc acted as a counter-ion in 4. Furthermore, topologic, thermal, optical and photoluminescence spectra of the compounds were studied in detail.

     

Three hydrogen-bonded nanotubular zinc(II) complexes of N-(9-anthracenyl)-N′-(4-pyridyl)-urea

Three hydrogen-bonded nanotubular zinc(II) complexes of a monodentate ligand N-(9-anthracenyl)-N′-(4-pyridyl)urea (L), [Zn(OAc)₂L₂]?H₂O (1), [ZnBr(OAc)L₂]?H₂O (2) and [ZnCl(OAc)L₂]?4H₂O (3), were synthesized and structurally characterized. In the complexes, the central metal ion is tetrahedrally coordinated by the pyridyl nitrogen atoms of two ligands and different anions, while the urea groups of the ligands self-associate into the typical urea tape through R₂¹(6) hydrogen bonds, which are essential for the formation of the nanotubes. The fluorescence properties of ligand L and the complexes were studied in the solid state at room temperature.     

Self-Recognition of 3D Porous Frameworks: Fourfold Diamondoid or Threefold Cuboidal Interpenetrating Nets Formed by Varying Pillar Motifs

Compound [Ni(2,6-ndc)(bpe)(H₂O)] _n (1) was prepared by the hydrothermal reaction of 2,6-naphthalenedicarboxylic acid (2,6-H₂ndc) and trans-1,2-bis(4-pyridyl)ethylene (bpe) with Ni(NO₃)₂·6H₂O under alkaline (NaOH) conditions. Treatment of 2,6-H₂ndc, 4,4′-bipyridine (4,4′-bpy) with M(NO₃)₂·6H₂O (M = Ni or Co) under similar conditions afforded compounds [Ni₂(2,6-ndc)₂(4,4′-bpy)] _n (2) and [Co₂(2,6-ndc)₂(4,4′-bpy)] _n (3), respectively. A single-crystal X-ray diffraction study revealed that compound 1 adopts a 3D fourfold interpenetrating diamondoid network stabilized by inter-net OH···O hydrogen bonds. The anionic 2,6-ndc ligand presents two different bonding characteristics, bis(monodentate) and bis(chelating bidentate) modes. A solid-state structural analysis revealed that compounds 2 and 3 are isomorphous and isostructural. Both present a 3D threefold interpenetrating cuboidal framework, consisting of a 2D (4,4)-net of interconnected [M ₂(O₂C)₄] (M = Ni, Co) paddle-wheel dinuclear units, and pillared by 4,4′-bpy ligands. The degree of interpenetration of these compounds could be adjusted successfully by varying only the organic pillar motifs.     

The Synthesis,Crystal and Molecular Structure,and Oxidation State of Iron Complex from Pyridoxal Isonicotinoyl Hydrazone and Ferrous Sulphate

The reaction of isonicotinoyl hydrazone of pyridoxal (PIH), a biologically active iron-carrier, with FeSO₄-7H₂0 at pH ∼ 6 generates the delta, lamda species of the N,N-trans-O,O-cis-cis coordination isomer of an iron(III) complex with iron-to-ligand ratio of 1:2. The dark red-brown crystals are monoclinic, space group C2/c, with unit-cell dimensions a = 14.487(2), b = 18.586(2), c = 27.508(4) Å, β = 102.76(3)°, and Z = 8. The coordination around the metal is distorted octahedral and involves the protonated organic ligands, which are chelated through the phenolic oxygen [Fe-O1 1.941(6), Fe-O1′ 1.938(6)], an enolic form of the carbonyl oxygen [Fe-O3 2.017(6), Fe-O3′ 2.018(6)] and the azomethinic nitrogen [Fe-N2 2.133(8), Fe-N2′ 2.133(8)]. Packing is determined by systems of N-H….O and O-H….O hydrogen bonds involving the protonated pyridoxal nitrogens, the pyridoxal hydroxymethyl group, and the [SO₄]²⁻ group. The Mössbauer spectra at different temperatures (300 K, 88 K and 4.1 K) clearly prove that the iron atom in the complex is in a high-spin trivalent state.     

Catalytic Behavior of Bis(Pyrrolide-Imine) and Bis(Phenoxy-Imine) Titanium Complexes for the Copolymerization of Ethylene with Propylene, 1-Hexene,or Norbornene

This contribution reports the catalytic behavior of bis(pyrrolide-imine)Ti complexes 1 and 2 , [2-(RNCH)-C₄H₃N]₂TiCl₂ ( 1 , R = Ph; 2 , R = cyclohexyl), and bis(phenoxy-imine)Ti complex 3 , [2-(Ph-NCH)-3-t Bu-C₆H₃O]₂TiCl₂ for the copolymerization of ethylene with propylene, 1-hexene, or norbornene. An inspection of the X-ray structures of complexes 1–3 suggested that complexes 1 and 2 with pyrrolide-imine ligands would provide more space for olefin polymerization than complex 3 with phenoxy-imine ligands. In addition, DFT calculations also showed that active species derived from complexes 1 and 2 possess higher electrophilicity of the Ti center compared to that from complex 3 . Complexes 1 and 2 on activation with methylalumoxane (MAO) had higher affinity for propylene and 1-hexene and incorporated higher amounts of propylene ( 1 ; 30.5 mol%, 2 ; 23.4 mol%) and 1-hexene ( 1 ; 1.9 mol%, 2 ; 1.7 mol%) than complex 3 (propylene; 4.5 mol%, 1-hexene; 0.4 mol%). The incorporation levels of propylene and 1-hexene displayed by complexes 1 and 2 were lower than those for Cp₂TiCl₂ (propylene; 41.6 mol%, 1-hexene; 5.1 mol%) under identical conditions. In contrast, complexes 1 and 2 exhibited higher incorporation ability for norbornene and produced copolymers with much higher norbornene contents ( 1 ; 32.0 mol%, 2 ; 26.5 mol%) than Cp₂TiCl₂ (1.2 mol%) under the same conditions. Additionally, complex 3 also promoted higher norbornene incorporation (4.3 mol%) than Cp₂TiCl₂ and provided a copolymer with extremely narrow molecular weight distribution (M_w/M_n 1.14). A correlation exists between electrophilicity of the Ti center in active species and norbornene incorporation.     

Highly Enantioselective Hydrogenation of Quinoline and Pyridine Derivatives with Iridium‐(P‐Phos) Catalyst

The use of a chiral iridium catalyst generated in situ from the (cyclooctadiene)iridium chloride dimer, [Ir(COD)Cl]₂, the P‐Phos ligand [4,4′‐bis(diphenylphosphino)‐2,2′,6,6′‐tetramethoxy‐3,3′‐bipyridine] and iodine (I₂) for the asymmetric hydrogenation of 2,6‐substituted quinolines and trisubstituted pyridines [2‐substituted 7,8‐dihydroquinolin‐5(6H)‐one derivatives] is reported. The catalyst worked efficiently to hydrogenate a series of quinoline derivatives to provide chiral 1,2,3,4‐tetrahydroquinolines in high yields and up to 96% ee. The hydrogenation was carried out at high S/C (substrate to catalyst) ratios of 2000–50000, reaching up to 4000 h⁻¹ TOF (turnover frequency) and up to 43000 TON (turnover number). The catalytic activity is found to be additive‐controlled. At low catalyst loadings, decreasing the amount of additive I₂ was necessary to maintain the good conversion. The same catalyst system could also enantioselectively hydrogenate trisubstituted pyridines, affording the chiral hexahydroquinolinone derivatives in nearly quantitative yields and up to 99% ee. Interestingly, increasing the amount of I₂ favored high reactivity and enantioselectivity in this case. The high efficacy and enantioselectivity enable the present catalyst system of high practical potential.     

From Overcrowded Polycyclic Aromatic Enes to Semifullerenes

Bi-9H-fluoren-9-ylidene (2) and bi-4H-cyclopenta[def]phenanthren-4-ylidene (5) are potential starting materials for the preparation of bowl-shaped fragments of fullerenes. Semiempirical MNDO-PM3 calculations of C₂₆H_n and C₃₀H_n (n = 12, 14, 16) species 2-12 are used to analyze energetic effects on the dehydrocyclization and isomerization reactions of these species. Oxidative photocyclizations on Z-2,2′-bridged derivatives of 2 and 5 are briefly outlined.     

2,2′-Bipyridine-Modified Tamoxifen: A Versatile Vector for Molybdacarboranes

Investigations on the antitumor activity of metallacarboranes are sparse in the literature and limited to a handful of ruthena- and molybdacarboranes. In this study, the molybdacarborane fragment [3-(CO)₂-closo-3,1,2-MoC₂B₉H₁₁] was combined with a vector molecule, inspired by the well-known drug tamoxifen or 4,4′-dihydroxytamoxifen (TAM-diOH). The molybdacarborane derivative [3,3-{4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine-κ²N,N′}-3-(CO)₂-closo-3,1,2-MoC₂B₉H₁₁] ( 10 ), as well as the ligand itself 4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine ( 6 ) showed cytotoxic activities in the low micromolar range against breast adenocarcinoma (MDA-MB-231, MDA-MB-361 and MCF-7), human glioblastoma (LN-229) and human glioma (U-251) cell lines. In addition, compounds 6 and 10 were found to induce senescence and cytodestructive autophagy, lower ROS/RNS levels, but only the molybdacarborane 10 induced a strong increase of nitric oxide (NO) concentration in the MCF-7 cells.     

Variations in binding modes of 2-mercaptobenzoxazolates in the novel cyclic trinuclear complexes [Mn3(CO)10(μ-SCNOC6H4)3] and [Re3(CO)12(μ-SCNOC6H4)3]

From reactions of [M₂(CO)₈(MeCN)₂] (MMn, Re) with 2-mercaptobenzoxazol, trinuclear clusters [Mn₃(CO)₁₀(μ-SCNOC₆H₄)₃] and [Re₃(CO)₁₂(μ-SCNOC₆H₄)₃] have been isolated; the former contains 2-mercaptobenzoxazolate ligands in three different binding modes, while in the latter all three bridge rhenium centres by S,N-coordination, but the three rhenium atoms all have different coordination environments.     

Corrosion inhibition of mild steel by benzotriazole derivatives in acidic medium

Benzotriazole derivatives, namely, N-[1-(benzotriazolo-1-yl)alkyl] aryl amine (BTMA), N-[1-(benzotriazolo-1-yl)aryl] aryl amine (BTBA), and 1-hydroxy methyl benzotriazole (HBTA), were synthesized and their inhibition behaviour on mild steel in 0.5 M H₂SO₄ at room temperature was investigated by various techniques. Preliminary screening of the inhibition efficiency (IE) was carried out using weight-loss measurements. Potentiodynamic polarization and AC impedance studies were used to investigate the inhibitor mechanism. Benzotriazole derivatives were found to act as mixed type inhibitors. Among the compounds studied, HBTA exhibited the best performance giving more than 95% IE in H₂SO₄ solutions. The passive film characterization was done using FTIR spectrum.     

Evaluation of 5H-Thiazolo[3,2-α]pyrimidin-5-ones as Potential GluN2A PET Tracers

We describe here our efforts to develop a PET tracer for imaging GluN2A-containing NMDA receptors, based on a 5H-thiazolo[3,2-α]pyrimidin-5-one scaffold. The metabolic stability and overall properties could be optimized satisfactorily, although binding affinities remained a limiting factor for in vivo imaging. We nevertheless identified 7-(((2-fluoroethyl)(3-fluorophenyl)amino)-methyl)-3-(2-(hydroxymethyl)cyclopropyl)-2-methyl-5H-thiazolo-[3,2-α]pyrimidin-5-one ([¹⁸F] 7b ) as a radioligand providing good-quality images in autoradiographic studies, as well as a tritiated derivative, 2-(7-(((2-fluoroethyl)(4-fluorophenyl)amino)methyl)-2-methyl-5-oxo-5H-thiazolo[3,2-α]pyrimidin-3-yl)cyclopropane-1-carbonitrile ([³H₂] 15b ), which was used for the successful development of a radioligand binding assay. These are valuable new tools for the study of GluN2A-containing NMDA receptors, and for the optimization of allosteric modulators binding to the pharmacophore located at the dimer interface of the GluN1-GluN2A ligand-binding domain.     

Tuning structural topologies of two coordination polymers via alter N-donor auxiliary ligand

Based on the N-donor auxiliary ligand effect, two new Ni(II) coordination polymers [Ni₂(HL)₂(bpe)₂] (1) and [Ni(HL)(bipy)(H₂O)₂] (2) [H₃L = 2-(4′-carboxyphenyl)terephthalic acid; bpe = 1,2-bis(4-pyridyl)ethane; bipy = 4,4′-bipyridine] have been successfully synthesized and characterized by single-crystal X-ray diffraction study, elemental analysis, IR spectra, TGA and powder X-ray diffraction (PXRD). This work presents a comparative study on the tuning of structural topologies by using two N-donor ligands with different lengths as auxiliary ligands. The structural determination reveals that complex 1, incorporating bpe ligands, features a three-dimensional (3D) 4-connected 4-fold dia interpenetrating architecture with the point symbol of 6⁶, while 2, containing bipy ligands, exhibits a two-dimensional (2D) sql layer structure with a 4-connected (4⁴·6²) topology. Moreover, the magnetic properties for 1 and 2 were also measured and compared on account of their different structures.