Unexpected Performance of a Bifunctional Sensitizer/Activator Component for Photon Energy Management via Upconversion.

We here report on the observation of upconverted photoluminescence (UC-PL) from the blue-light-emitting 9,10-diphenylanthracene (DPA) mixed with the yellow-light-absorbing bifunctional sensitizer/activator component of (3,3,7,8,12,13,17,18-octaethylporphyrin-22,24-diid-2-one) Pt (PtOEP-K). Yellow-to-blue UC-PL (0.680 eV spectral upshift) is achieved at room temperature under ultralow power continuous incoherent photoexcitation (220 μW/cm) despite the absence of triplet energy transfer (TET) between PtOEP-K and DPA.

Synthesis of Canthin-4-ones and Isocanthin-4-ones via B Ring Construction.

Canthin-4-one is synthesized via a six-step procedure starting from commercially available 3-amino-4-bromopyridine in 26% overall yield. 3-Amino-4-bromopyridine is initially converted to 8-bromo-1,5-naphthyridin-4(1)-one. O-Methylation, intermolecular Pd-catalyzed C-C coupling, and demethylation afford the key intermediate, 8-(2-chlorophenyl)-1,5-naphthyridin-4(1)-one, for which intramolecular C-N coupling completes the synthesis of the canthin-4-one skeleton.

The Photochemical Mediated Ring Contraction of 4-1,2,6-Thiadiazines To Afford 1,2,5-Thiadiazol-3(2)-one 1-Oxides.

1,2,6-Thiadiazines treated with visible light and O under ambient conditions are converted into difficult-to-access 1,2,5-thiadiazole 1-oxides (35 examples, yields of 39-100%). Experimental and theoretical studies reveal that 1,2,6-thiadiazines act as triplet photosensitizers that produce O and then undergo a chemoselective [3 + 2] cycloaddition to give an endoperoxide that ring contracts with selective carbon atom excision and complete atom economy. The reaction was optimized under both batch and continuous-flow conditions and is also efficient in green solvents.

Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis.

This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition patterns across the 60-cell line panel of the NCI Developmental Therapeutics Program (DTP). Many natural products and synthetic analogues are revealed as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates, through correlations to dipyridoimidazo[5,4-]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of the active compound with benzo[]perimidines, phenoxazinones, benz[]pyrido[1,2-]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-]naphthoquinones, hypothesised as prodrugs.

Metal-Free Organic Radical Spin Source.

Organic radicals have long been suggested as candidates for organic magnets and components in organic spintronic devices. Herein, we demonstrate spin current emission from an organic radical film via spin pumping at room temperature. We present the synthesis and the thin film preparation of a Blatter-type radical with outstanding stability and low roughness.

Mechanistic origins of methyl-driven Overhauser DNP.

The Overhauser effect in the dynamic nuclear polarization (DNP) of non-conducting solids has drawn much attention due to the potential for efficient high-field DNP as well as a general interest in the underlying principles that enable the Overhauser effect in small molecules. We recently reported the observation of 1H and 2H Overhauser effects in H3C- or D3C-functionalized Blatter radical analogs, which we presumed to be caused by methyl rotation. In this work, we look at the mechanism for methyl-driven Overhauser DNP in greater detail, considering methyl librations and tunneling in addition to classical rotation.

The Effect of High Pressure on Polymorphs of a Derivative of Blatter's Radical: Identification of the Structural Signatures of Subtle Phase Transitions.

The effect of pressure on the α and β polymorphs of a derivative of Blatter's radical, 3-phenyl-1-(pyrid-2-yl)-1,4-dihydrobenzo[][1,2,4]triazin-4-yl, has been investigated using single-crystal X-ray diffraction to maximum pressures of 5.76 and 7.42 GPa, respectively.

Deciphering the ground state of a C-symmetrical Blatter-type triradical by CW and pulse EPR spectroscopy.

3,3',3''-(Benzene-1,3,5-triyl)tris(1-phenyl-1H-benzo[e][1,2,4]triazin-4-yl) (1) is a C-symmetrical triradical comprised of three Blatter radical units connected at the 1, 3, 5 positions of a central trimethylenebenzene core. This triradical has an excellent air, moisture, and thermal stability. Single-crystal XRD indicates that triradical 1 adopts a propeller-like geometry with the benzotriazinyl moieties twisted by 174.

Synthesis and evaluation of 1,2,3-dithiazole inhibitors of the nucleocapsid protein of feline immunodeficiency virus (FIV) as a model for HIV infection.

We disclose a series of potent anti-viral 1,2,3-dithiazoles, accessed through a succinct synthetic approach from 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt). A series of small libraries of compounds were screened against feline immunodeficiency virus (FIV) infected cells as a model for HIV. This approach highlighted new structure activity relationship understanding and led to the development of sub-micro molar anti-viral compounds with reduced toxicity.

Methyl-Driven Overhauser Dynamic Nuclear Polarization.

The Overhauser effect is unique among DNP mechanisms in that it requires the modulation of the electron-nuclear hyperfine interactions. While it dominates DNP in liquids and metals, where unpaired electrons are highly mobile, Overhauser DNP is possible in insulating solids if rapid structural modulations are linked to a modulation in hyperfine coupling. Herein, we report that Overhauser DNP can be triggered by the strategic addition of a methyl group, demonstrated here in a Blatter's radical.

8,8'-(Benzo[][1,2,5]thiadiazole-4,7-diyl)bis(quinolin-4(1)-one): a twisted photosensitizer with AIE properties.

A new benzothiadiazole (BTZ) luminogen is prepared the Suzuki-Miyaura Pd-catalysed C-C cross-coupling of 8-iodoquinolin-4(1)-one and a BTZ bispinacol boronic ester. The rapid reaction (5 min) affords the air-, thermo-, and photostable product in 97% yield as a yellow precipitate that can be isolated by filtration. The luminogen exhibits aggregated-induced emission (AIE) properties, which are attributed to its photoactive BTZ core and nonplanar geometry.

A first-order phase transition in Blatter's radical at high pressure.

The crystal structure of Blatter's radical (1,3-diphenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl) has been investigated between ambient pressure and 6.07 GPa. The sample remains in a compressed form of the ambient-pressure phase up to 5.

Synthesis and Evaluation of Novel 1,2,6-Thiadiazinone Kinase Inhibitors as Potent Inhibitors of Solid Tumors.

A focused series of substituted 4-1,2,6-thiadiazin-4-ones was designed and synthesized to probe the anti-cancer properties of this scaffold. Insights from previous kinase inhibitor programs were used to carefully select several different substitution patterns. Compounds were tested on bladder, prostate, pancreatic, breast, chordoma, and lung cancer cell lines with an additional skin fibroblast cell line as a toxicity control.

Crystal Structure and Solid-State Packing of 4-Chloro-5-1,2,3-dithiazol-5-one and 4-Chloro-5-1,2,3-dithiazole-5-thione.

The crystal structure and solid-state packing of 4-chloro-5-1,2,3-dithiazol-5-one and two polymorphs of 4-chloro-5-1,2,3-dithiazole-5-thione were analyzed and compared to structural data of similar systems. These five-membered S,N-rich heterocycles are planar with considerable bond localization. All three structures demonstrate tight solid-state packing without voids which is attributed to a rich network of short intermolecular electrostatic contacts.

Design and evaluation of 1,2,3-dithiazoles and fused 1,2,4-dithiazines as anti-cancer agents.

Heteroatom rich 1,2,3-dithiazoles are relatively underexplored in medicinal chemistry. We now report screening data on a series of structurally diverse 1,2,3-dithiazoles and electronically related 1,2,4-dithiazines with the aim of identifying interesting starting points for potential future optimisation. The 1,2,3-dithiazoles, were obtained via a number of different syntheses and screened on a series of cancer cell lines.

Synthesis and Chemistry of Benzo[][1,2,6]thiadiazino[3,4-][1,4]diazepin-10(11)-ones and Related Ring Transformations.

2-[(3,5-Dichloro-4-1,2,6-thiadiazin-4-ylidene)amino]benzamides are cyclized to benzo[][1,2,6]thiadiazino[3,4-][1,4]diazepin-10(11)-ones via (i) treatment with NaH and via (ii) Pd-catalyzed C-N coupling. The behavior of the latter toward nucleophiles and thermal, oxidative, and reductive conditions revealed unexpected transformations to 3,5-dioxo-4,5-dihydro-3-benzo[][1,4]diazepine-2-carbonitrile and 2-(4-substituted-1,2,5-thiadiazol-3-yl)quinazolin-4(3)-ones.

Regioselective Fluorination of 7-Oxo-1,2,4-benzotriazines Using Selectfluor.

7-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this article, we provide the first synthesis of fluorinated derivatives. Fluorination using Selectfluor of benzo[1,2,4]triazin-7-ones occurs regioselectively and in high yield at the enamine-activated position.

Redox Active Quinoidal 1,2,4-Benzotriazines.

Modifying the para-quinonimine 1,3-diphenyl-1,2,4-benzotriazin-7(1 H)-one (2a) ( E -1.20 V), by replacing the N1-phenyl by pentafluorophenyl, the C3-phenyl by trifluoromethyl, or the C7 carbonyl by ylidenemalononitrile, led to improved electron affinities as determined by cyclic voltammetry and computational studies. Combining structural changes further improved electron accepting abilities: the most electron deficient analogues ( E ∼ -0.

The Conversion of 5,5'-Bi(1,2,3-dithiazolylidenes) into Isothiazolo[5,4-]isothiazoles.

Thermolysis of 4,4'-dichloro-, 4,4'-diaryl-, and 4,4'-di(thien-2-yl)-5,5'-bi(1,2,3-dithiazol-ylidenes) affords the respective 3,6-dichloro-, 3,6-diaryl- and 3,6-di(thien-2-yl)isothiazolo[5,4-]-isothiazoles in low to high yields. The transformation of the 4,4'-diaryl- and 4,4'-di(thien-2-yl)-5,5'-bi(1,2,3-dithiazolylidenes) occurs at lower temperatures in the presence of the thiophiles triphenylphosphine or tetraethylammonium iodide. Optimized reaction conditions and a mechanistic rationale for the thiophile-mediated ring transformation are presented.

1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors.

We demonstrate for the first time that 4-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors.

Synthesis and Characterization of Isodiphenylfluorindone and Isodiphenylfluorindinone.

Isodiphenylfluorindone 6 and isodiphenylfluorindinone 7 are synthesized. The former reacts with NaOMe to give the 13-methoxyisodiphenylfluorindone 22 (95%), while the latter reacts with 70% perchloric acid to give the bisperchlorate 21 (87%) and with MnO dimerizes to give 13,13'-bi(isodiphenylfluorindone) 4 (60%). UV-vis, NMR, CV, and DFT computational studies support the structural assignments of all products.

Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors.

Cell viability studies for benzo[1,2,4]triazin-7-ones and 1,2,4-benzotriazinyl (Blatter-type) radical precursors are described with comparisons made with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). All of the stable free radicals were several orders of magnitude less cytotoxic than the benzo[1,2,4]triazin-7-ones. The synthesis and evaluation of two new pyrid-2-yl benzo[1,2,4]triazin-7-ones are described, where altering the 1,3-substitution from phenyl to pyrid-2-yl increased cytotoxicity against most cancer cell lines, as indicated using National Cancer Institute (NCI) one-dose testing.