Diazocine Derivatives Research Articles

Synthesis and Photochromism of Diazocine Derivatives: Relationship Between Photoswitching Properties and Molecular Structures

Synthesis and Photochromism of Diazocine Derivatives: Relationship Between Photoswitching Properties and Molecular Structures

Evaluation of Biological Activity of a Diazocine Derivative against Heart Failure Using an Ischemia-Reperfusion Injury Model.

There are studies, which suggest that some diazocine derivatives can exert effects on the cardiovascular system; however, these effects are not very clear. The aim of this research was to evaluate the biological activity of a diazocine derivative against heart failure translated as area infarct. Biological activity produced by diazocine derivatives against heart failure was determinate using an ischemia/reperfusion injury model. Besides, to characterize the molecular mechanism of effect exerted by diazocine derivative on left ventricular pressure (LVP) was determinate in an isolated rat heart model using nifedipine, PINAME TXA2, and quinalizarin as controls. The results showed that diazocine derivative decrease the infarct area and increase the LVP. However, the effect produced by diazocine derivative on LVP was inhibited in the presence of quinalizarin. The results indicate that biological activity produced by diazocine derivative on left ventricular pressure is through protein CK2 activation; this phenomenon could be translated as a decrease in both infarct area and heart failure.

Synthesis of Chiral Diazocine Derivatives via a Copper-Catalyzed Dearomative [5+3] Cycloaddition.

Copper-catalyzed [5+3] cycloaddition of N-aromatic zwitterions and enol diazoacetates produced enantio-enriched diazocine derivatives. A sterically encumbered BOX ligand and NaBArF additive played significant roles in driving the overall catalytic process via the unfavorable dearomatization to construct the desired eight-membered heterocyclic compounds. The induced stereoselectivity was preserved after further modifications of the skeleton, which demonstrates the potential applications of the developed asymmetric catalysis.

Reduction of photoswitched, nitrogen bridged N-acetyl diazocines limits inhibition of 17βHSD3 activity in transfected human embryonic kidney 293 cells

Testosterone depletion is a common aim in the treatment of hormone-dependent prostate cancer, since the steroid boosts the tumor's proliferation. Therefore, inhibition of 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3), which catalyzes the carbonyl reduction of androstenedione to testosterone, represents an expedient therapeutic drug target. Among the compounds targeting 17βHSD3, tetrahydrodibenzazocines have been reported to be highly potent inhibitors. Thus, we hypothesized that structural analogs to the tetrahydrodibenzazocine scaffold, namely diazocines, which contain an azo group instead of the ethylene moiety, are also able to inhibit 17βHSD3. Diazocines consist of a photoresponsive core and can be isomerized from Z into E configuration by irradiation with a specific wavelength. In the present study, 17βHSD3 inhibition by diazocine photoisomers was examined in transfected human embryonic kidney 293 cells (HEK-293) and isolated microsomes. For this purpose, cells or microsomes were treated with androstenedione and incubated for 2 or 24 h in the presence or absence of irradiated and non-irradiated diazocines. Testosterone formation was determined by uHPLC. We report a weak inhibition of 17βHSD3 activity by diazocines in HEK-293 cells and microsomes. Furthermore, we found no significant difference between samples treated with irradiated and non-irradiated diazocines in terms of inhibition. However, we detected a new compound by HPLC analysis, which only appeared in light-treated samples, indicating a chemical modification of the photoswitched diazocines, presumably rendering them ineffective. Further investigations revealed that this modification occurs in the presence of reducing agents like dithiothreitol and glutathione. A preliminary mass-spectrometric analysis suggests that the N–N double bond is reduced, resulting in a dianiline derivative. Nevertheless, optimized photoswitchable diazocine derivatives, which are stable in a cellular environment, might serve as potent 17βHSD3 inhibitors, effective only in irradiated tissue.

Visible-light-driven photocontrol of the Trp-cage protein fold by a diazocine cross-linker.

Diazocines are characterized by extraordinary photochemical properties rendering them of particular interest for switching the conformation of biomolecules with visible light. Current developments afford synthetic access to unprecedented diazocine derivatives promising particular opportunities in photocontrol of proteins and biological systems. In this work, the well-established approach of photocontrolling the secondary structure of α-helices was exploited using a diazocine to reversibly fold and unfold the tertiary structure of a small protein. The protein of choice was the globulary folded Trp-cage, a widely used model system for the elucidation of protein folding pathways. A specifically designed, short and rigid dicarboxy-functionalized diazocine-based cross-linker was attached to two solvent-exposed side chains at the α-helix of the miniprotein through the use of a primary amine-selective active ester. This cross-linking strategy is orthogonal to the common cysteine-based chemistry. The cross-linked Trp-cage was successfully photoisomerized and exhibited a strong correlation between protein fold and diazocine isomeric state. As determined by NMR spectroscopy, the cis-isomer stabilized the fold, while the trans-isomer led to complete protein unfolding. The successful switching of the protein fold in principle demonstrates the ability to control protein function, as the activity depends on their structural integrity.

Diazocine Derivatives: A Family of Azobenzenes for Photochromism with Highly Enhanced Turn-On Fluorescence.

π-Conjugated azobenzene derivatives were reported to couple azo moieties with aryl fluorophore. Using the photochemistry of the C2-bridged azobenzene, we have accomplished two diazocine-based photoswitching molecules (cAz1 and cAz2). In addition to remarkable photochromic properties, they show a turn-on fluorescence, and the emission was highly enhanced with quantum efficiency increasing up to 0.22 for cAz1. The emission remains persistent and can only be switched off via thermal deactivation. They display greater optical responses, compared with the linear analogues (Az1-Az4). This work may provide a new scaffold toward advanced light-emitting materials using photoswitchable systems.

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer-Mills reactions.

Herein we report a reliable method to synthesize mono-functionalized S-diazocines in reproducible yields via intramolecular Baeyer–Mills reactions. Diazocines exhibit excellent photoswitchable properties. As opposed to azobenzenes they are more stable in their cis configuration. Particularly in photopharmacology mono-functionalized diazocines should be potentially useful and superior to the frequently used azobenzenes because the sterically more demanding cis configuration should be inactive, and the slender trans configuration should fit in a tight binding pocket of a receptor. Hence, it should be possible to administer the stabile inactive compound and switch it on at the site of illness with visible light. To date only a limited number of diazocine derivatives have been published of which most are symmetrically functionalized. Using the Baeyer–Mills reaction for the synthesis of diazocines opens a novel and convenient access to unsymmetrically substituted diazocines.

Amine‐Substituted Diazocine Derivatives – Synthesis, Structure, and Photophysical Properties

A series of amine-substituted diazocines were synthesized in three steps from methyl 2-aminobenzoate or methyl 3-aminonaphtholate. The saddle-shaped diazocine compounds showed similar interplane angle of 75° despite the different steric bulk of the amine substituents. In electrochemical experiments, these diazocines showed irreversible reduction most likely producing indolo[3,2-b]indoles rather than forming the 10-electron planar aromatic species. The carbazole-substituted naphthodiazocines showed the most interesting photophysical properties with evidence of transition from the saddle-shaped ground state to a planar excited state geometry.

Synthesis and electroluminescent properties of new diazocine derivatives

ABSTRACTDAPCz and DANaPCz have been successfully synthesized and characterized. DAPCz and DANaPCz in film state showed absorption in the range of 322 to 345 nm wavelength and exhibited blue photoluminescence (PL) emission peaks at 428 and 425 nm. PL wavelength of DAPCz is red-shifted by 3 nm than that of DANaPCz, which is due to the carbazole electron donating group of DAPCz. The use of DAPCz in a non-doped OLED device resulted in blue emission with current efficiency of 1.01 cd/A and C.I.E. of (0.26, 0.37).

Synthesis and property of diazocine derivatives substituted with imidazole in various positions

ABSTRACTTIACA-I, TIACA-II were synthesized by changing the substitution position of the imidazole group in the diazocine core. TIACA-I, TIACA-II in the film state showed absorption in the range of 354 to 392 nm and exhibited blue photoluminescence (PL) emissions at 448 and 462 nm, respectively. The PL wavelength of TIACA-II is red-shifted by 14 nm than that of TIACA-I due to the electron-donating intensity depending on the position of the imidazole group. The use of TIACA-II in a non-doped OLED device resulted in blue emission with current efficiency of 2.84 cd/A and CIE of (0.15, 0.18).

Synthesis and electro-optical properties of diazocine derivatives based on different positions of substituted naphthyl group

ABSTRACTThe new diazocine derivatives, 1-DAN and 2-DAN have been successfully synthesized and characterized. 1-DAN and 2-DAN, are different the positions of naphthyl substituted in the anthracene. In the film state, 1-DAN and 2-DAN exhibited absorption in the range of 354 to 402 nm and showed blue photoluminescence (PL) emission at 441 and 450 nm. The PL wavelength of 1-DAN was blue-shifted by 9 nm than that of 2-DAC. This is because the conjugation length is decreased by H atom-H atom repulsion between 1-naphthyl and anthracene. Organic light emitting diode (OLED) device using 2-DAN as emitting layer (EML) showed current efficiency of 1.76 cd/A.

Synthesis and property of diazocine derivatives substituted with imidazole including various chromophores

ABSTRACTThe new diazocine derivatives, 2,8-bis(4-(1-(4-(10-(naphthalene-2-yl)anthracen-9-yl)naphthalene-1-yl)-1H -phenanthro[9,10-d]imidazol-2-yl)phenyl)-6H, 12H-5,11-methanodibenzo[b,f][1,5]diazocine (NANIDZ-I) and (5S,11S)-2,8-bis(4-(1-(4-(10-(naphthalen-1-yl)anthracen-9-yl)naphtha-lene-1-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)-6H, 12H-5, 11-methanodibenzo[b,f][1,5]dizocine (NANIDZ-II) have been successfully synthesized and characterized. It has not only the characteristics of rigid, chiral and C2-symmetry but also charge transport capability and emission. NANIDZ-I and NANIDZ-II were synthesized by changing the substitution position of the imidazole group including various chromophore in the diazocine core. NANIDZ-I device in a non-doped organic light emitting diode resulted in blue emission with luminance efficiency of 4.29 cd/A and CIE of (0.17, 0.25).

Synthesis and property of diazocine derivatives substituted with carbazole in meta and para positions

ABSTRACTM-DAC and P-DAC have been successfully synthesized and characterized. The ultraviolet-visible (UV-Vis) absorption of M-DAC and P-DAC showed in the range of 373 nm to 394 nm and exhibited maximum photoluminescence (PL) emissions at 466 and 481 nm in the film state. PL wavelength of P-DAC is red-shifted by 15 nm than that of M-DAC. This is because carbazole is substituted for para position and the conjugation length is increased. M-DAC and P-DAC OLED devices exhibited current efficiency of 3.09 and 2.80 cd/A and C.I.E(x,y) values of (0.17, 0.27) and (0.18,0.33).

Reduction of imidazolium salts – An approach to diazocines and diazocanes

A convenient approach to diazocine derivatives 8,9 starting from 1,2-polymethyle-neimidazolium salts 4 was developed. The polymethylenimidazolium salts 4 are partially reduced with sodium borohydride in DMF to give 5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-a]imidazoles 5 or under more forcing conditions – (sodium triacetoxyborohydride in acetic acid) with cleavage of the endocyclic CN bond affording diamines 6. Tertiary salts 7 readily prepared from compounds 5 react with NaBH4 and KCN nucleophiles with cleavage of the endocyclic NC bond to form diazocine derivatives 8,9.

Synthesis and electroluminescent properties of diazocine derivatives

ABSTRACTFour new diazocine derivatives including anthracene moiety, 2,8-Bis-[3-(10-naphthalen-2-yl-anthracen-9-yl)-phenyl]-6H,12H-5, 11-methano-dibenzo[b,f][1,5]diazocine(AK14), 2,8-Bis-[2-(10-naphthalen-2-yl-anthrac-en-9-yl)-phenyl]-6H,12H-5,11-methano-dibenzo[b,f][1,5]diazocine(AK15), 2,8-Bis-[4-(10-phenyl-anthracen-9-yl)-phenyl]-6H,12H-5,11-methano-dib-enzo[b,f][1,5]diazocine(AK20), 2,8-Bis-[2-(10-phenyl-anthracen-9-yl)-ph-enyl]-6H,12H-5,11-methano-dibenzo[b,f][1,5]diazocine(AK21) were synth-esized. Those materials exhibited photoluminescence (PL) maximum value of about 411∼428 nm in solution state and 429∼483 nm in film state, respectively.Four compounds were used as EML in OLED device: ITO / 2-TNATA (60 nm) / NPB (15 nm) / EML (35 nm) / Alq3 (20 nm) / LiF / Al. OLED devices, fabricated by AK14, AK20 and AK21, showed the current efficiency with 2.16cd/A, 0.28cd/A and 1.56cd/A. The OLED device, fabricated by AK15, showed the best performance with 2.83cd/A, 1.25lm/W and CIE(x,y) = (0.16, 0.23).

ChemInform Abstract: Reactivity Control in the Addition of N,N′‐Dialkylated 1,n‐Diamines to Activated Skipped Diynes: Synthesis of Fused Bicyclic 1,4‐Diazepanes and 1,5‐Diazocanes.

AbstractA novel protocol for the synthesis of a new family of furodiazepine and ‐diazocine derivatives (IV) is developed using a metal‐free domino reaction of tertiary skipped diynes (I) with N,N‐dialkylated diamines (II).

ChemInform Abstract: Intramolecular Azide—Alkyne [3 + 2] Cycloaddition: A Versatile Route for the Synthesis of 1,2,3‐Triazole Fused Dibenzo[1,5]diazocine Derivatives.

AbstractThe simple procedure allows an easy isolation and purification of the products.

Intramolecular Azide-Alkyne [3+2] Cycloaddition: A Versatile Route for the Synthesis of 1,2,3-Triazole Fused Dibenzo[1,5]diazocine Derivatives

A facile synthesis of [1,2,3]triazolo dibenzo[1,5]diazocines by intramolecular Huisgen 1,3-dipolar cycloaddition of azide with alkynes has been achieved. The methodology offers clean reaction and easy isolation of products in excellent yields.

1,2,3,6-Tetrahydropyrrolo[1,2-d][1,4]diazocines. Reactions of 1-methyl-2-R-tetrahydropyrrolo[1,2-a]pyrazines with alkynes

The reactions of 6-formyl- and 6-trifluoroacetyl-1-methyl-2-R-tetrahydropyrrolo[l, 2-a]-pyrazines with activated alkynes in methanol and acetonitrile have been studied. Terahydro-pyrrolo[l,2-d][l,4]diazocine derivatives were synthesized at the first time.

Aminomethylene Ketones and Enamines in Heterocyclic Synthesis: Synthesis of Functionally Substituted Pyridine, Pyrazole, Fused Pyrimidine and Fused [1,5]Diazocine Derivatives

AbstractFor Abstract see ChemInform Abstract in Full Text.