Photocyclization of Diarylethenes: The Effect of Electron and Proton Acceptors as Additives.

The effect of electron and proton acceptors on the photocyclization of diarylethenes has been studied. Without any additives, the deprotonation reaction is predominant, although other processes, including the sigmatropic shift, are not excluded. A deuterium exchange experiment has shown that a strong base (DABCO) facilitates the deprotonation reaction, thereby limiting the sigmatropic shift. In the presence of an oxidizing agent or additional sources of radicals (O2, I2, TEMPO), the processes of deprotonation and rearrangement (H-shift) are practically not observed, and the reaction proceeds along a radical pathway with the formation of phenanthrene or its heterocyclic analogue.

Light-Sensitive Material Structure-Electrical Performance Relationship for Optical Memory Transistors Incorporating Photochromic Dihetarylethenes.

Photoswitchable organic field-effect transistors (OFETs) with embedded photochromic materials are considered as a promising platform for development of organic optical memory devices. Unfortunately, the operational mechanism of these devices and guidelines for selection of light-sensitive materials are still poorly explored. In the present work, a series of photochromic dihetarylethenes with a cyclopentenone bridge moiety were investigated as a dielectric/semiconductor interlayer in the structure of photoswitchable OFETs. It was shown that the electrical performance and stability of the devices can be tuned by variation of the substituents in the structure of the photochromic material. In particular, it was found that dihetarylethenes with donor substituents demonstrated the best light-induced switching effects (wider memory windows and higher switching coefficients) in the devices. The operation mechanism of the light-triggered memory devices was proposed based on the differential in situ Fourier transform infrared (FTIR) spectroscopy data and regression analysis of the threshold voltage-programming time experimental dependencies. The established relationships will facilitate further rational design of new photochromic materials, thus paving a way to fast and durable organic optical memories and memory transistors (memristors).

Benzimidazolyl-pyrazolo[3,4-b]pyridinones, Selective Inhibitors of MOLT-4 Leukemia Cell Growth and Sea Urchin Embryo Spiculogenesis: Target Quest.

1,3-Substituted pyrazolo[3,4-b]pyridinones 11-18 were synthesized by a three-component condensation of Meldrum's acid with aryl aldehydes and 1,3-substituted 5-aminopyrazoles. Their biological activity was evaluated using the in vivo phenotypic sea urchin embryo assay and the in vitro cytotoxicity screen against human cancer cell lines. In the sea urchin embryo model, 1-benzimidazolyl-pyrazolo[3,4-b]pyridinones 11 caused inhibition of hatching and spiculogenesis at sub-micromolar concentrations. These compounds also selectively and potently inhibited growth of the MOLT-4 leukemia cell line. Subsequent structure-activity relationship studies determined the benzimidazolyl fragment as an essential pharmacophore for both effects. We applied numerous techniques for target identification. A preliminary QSAR target identification search did not result in tangible leads. Attempts to prepare a relevant photoaffinity probe that retained potency in both assays were not successful. Compounds 11 were further characterized for their activity in a wild-type versus Notch-mutant leukemia cell lines, and in in vitro panels of kinases and matrix metalloproteinases. Using a series of diverse modulators of spiculogenesis as standards, we excluded multiple signaling networks including Notch, Wnt/ß-catenin, receptor tyrosine kinases (VEGF/VEGFR, FGF/FGFR), PI3K, and Raf-MEK-ERK as possible targets of 11. On the other hand, matrix metalloproteinase-9/hatching enzyme was identified as one potential target.

Spectral properties and structure of unsymmetrical diarylethenes based on thiazole ring with hydrogen at the reactive carbon.

Six new photoactive unsymmetrical diarylethenes bearing thiazole ring with hydrogen at the reactive carbon atom have been synthesized. Their structures have been studied by DFT calculations and X-ray crystallography. All compounds undergo irreversible photochemical transformations under irradiation with ultraviolet light, proceeding through the photocyclization stage. It has been found that only some normal (thiophene, imidazole and pyrazole derivatives) and inverse type (oxazole derivative) diarylethenes form colored photoinduced isomers under UV. In polar acetonitrile these intermediates show relatively fast irreversible thermal reaction, while in nonpolar toluene slow cycloreversion to initial diarylethenes is the predominant process of these species.

Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies.

A series of 3,7-diaryl-6,7-dihydroisothiazolo [4,5-b]pyridin-5(4H)-ones 8 and 9 was synthesized by multicomponent condensation of 3-aryl-5-isothiazolecarboxylic acid esters 4a-f with aromatic (or thienyl) aldehydes 7 and Meldrum's acid in an acidic medium. The targeted compounds were evaluated for their antimitotic microtubule destabilizing activity using in vivo phenotypic sea urchin embryo model and in vitro human cancer cell-based assays. Selected dihydroisothiazolopyridinones altered sea urchin egg cleavage in 2-10 nM concentrations together with significant cytotoxicity against cancer cells including chemoresistant cell lines (IC50 in submicromolar - low nanomolar concentration range). Both approaches confirmed antimitotic microtubule destabilizing mechanism of action of the izothiazole derivatives. Structure-activity relationship study determined the importance of p-methoxybenzene A-ring for the antiproliferative effect. The most potent compound 9b containing p-methoxybenzene A-ring and thiophene B-ring caused mitotic arrest and disintegration of cell microtubules.

Facile Synthesis of Natural Alkoxynaphthalene Analogues from Plant Alkoxybenzenes.

Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (1) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (5) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay.

General Photoinduced Sequential Electrocyclization/[1,9]-Sigmatropic Rearrangement/Ring-Opening Reaction of Diarylethenes.

A novel and efficient photochemical transformation of diarylethenes comprising a five-membered heterocyclic ring and phenyl moiety is described. This reaction provides a simple method for the preparation of functionalized naphthalene derivatives via photorearrangement reaction of diarylethenes, and the process is characterized by high efficiency that was determined by NMR monitoring. Some mechanistic aspects of this process have been also explored. It was found that the reaction includes tandem transformation of three basic processes: the photocyclization of the hexatriene system, [1,9]-sigmatropic rearrangement, and heterocyclic ring opening. Diarylethenes with different heterocycle moieties (thiophene, benzo[b]thiophene, furan, indole, imidazole, thiazole, oxazole, pyrazole) have been involved into this process, and the target naphthalenes with good yields have been obtained. The opportunity for use in the transformation of diarylethenes with different heterocyclic residues permits synthesis of naphthalenes with desired functional groups. The general character and high efficiency of the reaction promise that the transformation can be an effective synthetic route for the annulation of benzene rings to various aromatic systems, including heterocycles.

Photoinduced skeletal rearrangement of diarylethenes comprising oxazole and phenyl rings.

A novel photochemical rearrangement of diarylethenes bearing oxazole and benzene derivatives as aryl moieties that results in the formation of polyaromatic systems was investigated. The mechanism of the transformation includes photocyclization, sequential [1,9] and [1,3]-hydrogen shifts, as well as a lateral oxazole ring-opening process. It was shown that this reaction can be an effective synthetically preparative method for the preparation of naphthalene (polyaromatic) derivatives.

Synthesis and comparative photoswitching studies of unsymmetrical 2,3-diarylcyclopent-2-en-1-ones.

Photochromic diarylethenes (DAEs) based on the unsymmetrical ethene "bridge" bearing heterocycles of the different nature (oxazole and thiophene) as aromatic moieties have been designed and the photoswitching properties have been studied. The comparative studies of the photochromic characteristics of unsymmetrical isomeric 2,3-diarylcyclopent-2-en-1-ones have shown that the isomers have different thermal stability, absorption maxima, and quantum yields. It was found that the unsymmetrical diarylcyclopentenone bearing at second position of the cyclopentenone ring the thiophene unit displays high thermally stability, hypsochromic shift of absorption maxima wavelengths of initial and cyclic forms, and high quantum yields of cyclization and cycloreversion reactions. The replacement of the carbonyl group with oxime leads to a reduction of the difference in the photochromic properties of these isomers and just as the reduction of the carbonyl group to the hydroxy-group negates this difference to zero. The intramolecular hydrogen bond formation in the oxime and hydroxy derivatives was confirmed by IR and (1)H NMR spectral analysis, but the increase of the quantum yields of the cyclization reaction in a nonpolar hexane is observed only in the case of hydroxy derivatives that can be explained by the formation of more rigid six-membered heterocycle in hydrogen bonding.

Synthesis and photochromic properties of oxime derivatives of 2,3-diarylcyclopent-2-en-1-ones.

A wide range of new oxime-based photochromic diarylethenes of the cyclopentenone series have been synthesized. Their spectral properties have been investigated in detail upon UV/vis light irradiation in acetonitrile solution, and distinct correlations between photochromic characteristics and substance structures are revealed. It was found that the introduction of an oxime group into the cyclopentene ring has a significant influence on the switching characteristics-primarily on the thermal stability, and a series of thermally stable oxime-based photochromic diarylcyclopentenones have been prepared. The results obtained suggest that the modifications of the ethene "bridge" are a promising way to tune the spectral parameters of diarylethenes in an accurate manner and thus to synthesize the photochromic compounds with desired properties.

Regio- and chemoselective bromination of 2,3-diarylcyclopent-2-en-1-ones.

The bromination of 2,3-diarylcyclopent-2-en-1-ones under various conditions has been studied. It was found that depending on the brominating reagent and nature of solvent the bromine atom can be introduced at the 4- or 5-position of the ethene "bridge", as well as into the aryl moieties. Aryl group bromination is accomplished with such reagents as molecular bromine, N-bromosuccinimide, or tetrabutylammonium tribromide. 5-Bromocyclopentenones with very high efficiency can be obtained by the reaction with copper(II) bromide in methanol, while 4-bromoketones are prepared in n-propyl acetate. The developed methods can be highly useful for the synthesis of bromo-substituted 2-cyclopenten-1-ones and their close analogues, which are important synthons in organic synthesis and for the preparation of a variety of useful substances.

Design, synthesis and structure-activity studies of rhodanine derivatives as HIV-1 integrase inhibitors.

Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties.

Coumarinyl(thienyl)thiazoles: novel photochromes with modulated fluorescence.

Novel photochromic 5-(3'-coumarinyl)-4-(3''-thienyl)thiazoles have been synthesized. These compounds display intensive fluorescence emission in the open form A, which is modulated by light. Fluorescence intensity decreases significantly upon irradiation of A with UV-light (lambda<400 nm) due to formation of the cyclic form B. Irradiation of B with visible light (lambda>470 nm) promotes its opening and the recovering of fluorescence. Novel dihetarylethenes undergo photochromic modulation of fluorescence both in solution and in polymeric matrices.