The Molecular Diversity of 1,8-diaminonaphthalene in Organic Chemistry.

BACKGROUND: 1,8-diaminonaphthalen (1,8-DAN) with special organic structure was applied in organic synthesis to provide efficient complex scaffolds, through the two or fourcomponent fashion. This review highlights its recent application in organic reactions under different conditions and heterogynous catalysts to produce various molecules, which were used as medicines, sensors, and dyes. OBJECTIVE: 1,8-diaminonaphthalene (1,8-DAN) is a bicyclic compound with two amino groups which has received much attention in organic chemistry due to their medicinal activities such as antifungal, antimicrobial, antiulcer, antitumor, oxidation dyestuff, hair color, fluorescent, and chemo-sensors. In continuation of our studies, herin, recent application of 1,8-DAN in organic synthesis was reviewed. CONCLUSION: In conclusion, the application of 1,8-DAN 1 in different reactions was reviewd through the various conditions to yield the target compounds with high medicinal activities, and potential for sensitive detection of different ions. The target compounds including 1,8-DAN 1 with various structures were provided such as perimidines, perimidinones, aminonaphthalenes which were produced through different methods as brought for further study in this review.

A novel near-infrared fluorescent probe for detection of early-stage Aß protofibrils in Alzheimer's disease.

Detection of Aß protofibrils at the early stage of Alzheimer's disease was realized by a novel near-infrared probe (DCM-AN) based on dicyanomethylene-4H-pyran. This probe exhibits high affinity towards Aß protofibrils in vitro and in brain sections of transgenic mouse models for Alzheimer's disease.

Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid-ß Plaques in Alzheimer's Disease.

Alzheimer's disease (AD) is pathologically characterized by the accumulation of ß-amyloid (Aß) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor-acceptor end groups interacting through a π-conjugated system for the detection of Aß deposits in the brain. Among these probes, 3b and 3c had excellent fluorescent properties (emission maxima > 650 nm and high quantum yields) and displayed high sensitivity and high affinities to Aß aggregates (3b, Kd = 8.8 nM; 3c, Kd = 1.9 nM). Both 3b and 3c could readily penetrate the blood-brain barrier with high initial brain uptake and fast to moderate washout from the brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type mice. In summary, our research provides new hints for developing smarter and more activatable NIR probes targeting Aß.

MitoBlue: a nontoxic and photostable blue-emitting dye that selectively labels functional mitochondria.

We report the discovery of a fluorogenic dye, N(1),N(3)-di(2-aminidonaphthalen-6-yl) propane-1,3-diamine, MitoBlue, which selectively stains functional mitochondria while displaying low toxicity, bright blue emission, and high resistance to photobleaching. Additionally, we show that a biotin-labeled MitoBlue derivative can be used as a handle for the delivery of streptavidin-tagged species to the mitochondria.

Synthesis of superparamagnetic iron oxide nanoparticles coated with a DDNP-carboxyl derivative for in vitro magnetic resonance imaging of Alzheimer's disease.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been proposed for use in magnetic resonance imaging as versatile ultra-sensitive nanoprobes for Alzheimer's disease imaging. In this work, we synthetized an efficient contrast agent of Alzheimer's disease using 1,1-dicyano-2-[6-(dimethylamino)naphthalene-2-yl]propene (DDNP) carboxyl derivative to functionalize the surface of SPIONs. The DDNP-SPIONs are prepared by conjugating DDNP carboxyl derivative to oleic acid-treated SPIONs through ligand exchange. The structure, size distribution and magnetic property were identified by IR, TGA-DTA, XRD, TEM, Zetasizer Nano and VSM. TEM and Zetasizer Nano observations indicated that the DDNP-SPIONs are relatively mono-dispersed spherical distribution with an average size of 11.7nm. The DDNP-SPIONs were then further analyzed for their MRI relaxation properties using MR imaging and demonstrated high T2 relaxivity of 140.57s(-1)FemM(-1), and the vitro experiment that DDNP-SPIONs binding to ß-Amyloid aggregates were then investigated by fluorophotometry, the results showed that the combination had induced the fluorescence enhancement of the DDNP-SPIONs and displayed tremendous promise for use as a contrast agent of Alzheimer's disease in MRI.

Solvatochromic pyrene analogues of Prodan exhibiting extremely high fluorescence quantum yields in apolar and polar solvents.

True colors: Novel pyrene analogues of Prodan exhibit outstanding photophysical properties with remarkably high fluorescence quantum yield (QY) in solvents ranging from apolar hexane to polar methanol (see figure). This is accompanied by strong solvatochromism and large Stokes shifts. These properties have not been previously achieved in enormous solvatochromic dyes, but are quite useful for emitting materials and imaging tools.

Characterization of a new series of fluorescent probes for imaging membrane order.

Visualization and quantification of lipid order is an important tool in membrane biophysics and cell biology, but the availability of environmentally sensitive fluorescent membrane probes is limited. Here, we present the characterization of the novel fluorescent dyes PY3304, PY3174 and PY3184, whose fluorescence properties are sensitive to membrane lipid order. In artificial bilayers, the fluorescence emission spectra are red-shifted between the liquid-ordered and liquid-disordered phases. Using ratiometric imaging we demonstrate that the degree of membrane order can be quantitatively determined in artificial liposomes as well as live cells and intact, live zebrafish embryos. Finally, we show that the fluorescence lifetime of the dyes is also dependent on bilayer order. These probes expand the current palate of lipid order-sensing fluorophores affording greater flexibility in the excitation/emission wavelengths and possibly new opportunities in membrane biology.

Heterocoupling of 2-naphthols enabled by a copper-N-heterocyclic carbene complex.

The reactivity of a Cu catalyst for oxidative coupling is modulated by a small molecule additive, diethyl malonate, that slows over-oxidation of 2-naphthols. Efficient heterocoupling between electron-rich and electron-poor 2-naphthols/2-naphthylamines affords C(1)-symmetric BINOLs with yields ranging from 35-98%.

Direct intermolecular aniline ortho-arylation via benzyne intermediates.

A method for direct, transition-metal-free ortho-arylation of anilines by aryl chlorides, bromides, fluorides, and triflates has been developed. This methodology provides the most direct approach to 2-arylanilines since no protecting or directing groups on nitrogen are required. The arylation is functional-group tolerant, with alkene, ether, trifluoromethyl, dimethylamino, carbonyl, chloro, and cyano functionalities tolerated. Phenylation of enantiopure binaphthyldiamine affords a product with >99% ee.

Interfacial synthesis and functionality of self-stabilized polydiaminonaphthalene nanoparticles.

A simple and effective template-free synthesis method for nanosized conducting polymers with self-stability and functionality is a main challenge. Herein, a strategy is reported for the facile synthesis of poly(1,5-diaminonaphthalene) nanospherical particles by an interfacial miniemulsion oxidative polymerization of 1,5-diaminonaphthalene at mobile microinterfaces between a stirred biphase without external emulsifiers. The size of the nanospheres was carefully optimized by controlling the polymerization conditions. Formation and self-stabilization mechanisms of the nanoparticles are proposed. The constantly movable and refreshed microinterface is a key to successful synthesis of the nanospheres, for significantly suppressing secondary growth leading to agglomerated particles because vigorous stirring makes as-formed self-stabilized nanospheres instantly leave the microinterfaces. The resulting nanospheres possess several advantages: clean surface, self-stability, redispersibility, semiconductivity, electroactivity, and fluorescence emission. The fluorescence emission can be quenched by specific quenchers, thus enabling low-cost, high-performance chemosensors to be obtained for the sensitive detection of Zn(II) ions in a wide linear concentration range of more than five orders of magnitude with a superior detection limit down to 1 nM.

Synthesis and biological evaluation of 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26).

The synthesis and potent inhibitory activity of novel 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-(4-(naphthalen-2-ylamino)phenyl)propyl derivatives vs a MCF-7 CYP26A1 microsomal assay is described. This study focused on the effect of modifying the heme binding azole group and the flexible C3 chain on inhibitory activity and selectivity. The most promising inhibitor 2,2-dimethyl-3-[4-(naphthalen-2-ylamino)-phenyl]-3-[1,2,4]triazol-1-yl-propionic acid methyl ester (17) (IC(50) = 0.35 nM as compared with liarozole IC(50) = 540 nM and R116010 IC(50) = 10 nM) was evaluated for CYP selectivity and hepatic stability. Compounds with CYP26 inhibitory IC(50) values ≤50 nM enhanced the biological activity of exogenous ATRA, as evidenced by a 3.7-5.8-fold increase in CYP26A1 mRNA in SH-SY5Y neuroblastoma cells as compared with ATRA alone. All compounds demonstrated an activity comparable with or better than R116010, and the induction correlated well with CYP26 inhibition data. These studies highlight the promising activity profile of this novel CYP26 inhibitor and suggest it as an appropriate candidate for future development.

Synthesis and pharmacological evaluation of the individual stereoisomers of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, a potent mast cell stabilising agent.

Each stereoisomer of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, 1a-d, was prepared and evaluated in vitro for its ability to prevent mediator release induced by different degranulating agents from rodent mast cells and also in vivo against passive cutaneous anaphylaxis. The manner in which the stereoisomers prevented direct membrane activation was found to be highly dependent on the stereochemistry of the individual isomers. Stereoisomer 1b was the most active isomer in vivo, exhibiting superior activity to disodium cromoglycate.

Does PRODAN possess an O-TICT excited state? Synthesis and properties of two constrained derivatives.

The synthesis and photophysical properties of 7-(dimethylamino)-3,4-dihydrophenanthren-1(2H)-one (7) and 3-(dimethylamino)-8,9,10,11-tetrahydro-7H-cyclohepta[a]naphthalen-7-one (8) are reported. These compounds possess a cycloalkanone substructure that controls the extent of twisting of the carbonyl group. The six-membered ring in 7 forces the carbonyl group to be coplanar with the naphthalene ring, whereas the seven-membered ring in 8 induces a significant twist. Both have the substructure of PRODAN (6-propionyl-2-(dimethylamino)naphthalene, 1). Comparing the photophysical behavior of these compounds with that of PRODAN and 2,2-dimethyl-1-(4-methyl-1,2,3,4-tetrahydrobenzo[f]quinolin-8-yl)propan-1-one (3) indicates that PRODAN likely emits from a PICT excited state rather than from an O-TICT excited state.

Synthesis and evaluation of dimeric 1,2,3,4-tetrahydro-naphthalenylamine and indan-1-ylamine derivatives with mast cell-stabilising and anti-allergic activity.

In a continuation of our studies into 4-Amino-3,4-dihydro-2H-naphthalen-1-ones as novel modulators of allergic and inflammatory phenomena, we have extended our work to include dimeric analogues. Of these derivatives, the most promising activity was seen with tertiary amine 58a, which exhibited potent mast cell-stabilising activity in vitro against a variety of stimuli and also in vivo against passive cutaneous anaphylaxis.

Solvation dynamics of the fluorescent probe PRODAN in heterogeneous environments: contributions from the locally excited and charge-transferred states.

The coexistence of different excited states with different properties of the same chromophores could have significant consequences for the accurate characterization of solvation dynamics in a heterogeneous environment, such as a protein. The purpose of this work is to study the contributions of the locally excited (LE) and charge-transferred (CT) states of the fluorescent probe molecule 6-propionyl-2-(N,N-dimethylamino)naphthalene (PRODAN) to its solvation dynamics in the heterogeneous environment provided by reverse micelles formed by sodium 1,4-bis-(2-ethylhexyl) sulfosuccinate (AOT)/n-heptane/water. We have found that the LE and CT states of PRODAN solvate on different time scales in reverse micelles (2 and approximately 0.4 ns, respectively), consistent with results suggested in the literature, and have concluded that PRODAN's use as a probe of heterogeneous environments must be used with caution and that, more importantly, the same caution must be exercised with any chromophore capable of emitting from different excited states.

Synthesis and spectroscopic studies on complexes of N,N'-bis-(2-pyridinecarboxaldimine)-1,8-diaminonaphthalene (L); DNA binding studies on Cu(II) complex.

The Schiff base ligand, N,N'-bis-(2-pyridinecarboxaldimine)-1,8-diaminonaphthalene (L), obtained by the condensation of 2-pyridinecarboxaldehyde and 1,8-diaminonaphthalene, has been used to synthesize the mononuclear complexes of the type [MLCl(2)] [M=Co(II), Ni(II), Cu(II) and Zn(II)]. The newly synthesized ligand (L) and its complexes have been characterized on the basis of results of elemental analysis, molar conductance, magnetic susceptibility measurements, Job's method and spectroscopic studies viz., FT-IR, Mass, (1)H and (13)C NMR. The UV-vis and magnetic moment data revealed an octahedral geometry around Co(II), Ni(II) and Cu(II) ions and conductivity data show a non-electrolytic nature of the complexes. Absorption and fluorescence spectroscopic studies support that Cu(II) complex exhibits significant binding to calf thymus DNA.

A Preparation of enantiomerically enriched axially chiral beta-diketimines: synthesis of (-)- and (+)-IAN amine.

The preparation of an enantiomerically enriched beta-diketimine composed of isoquinoline and 2-aminonaphthalene (IAN amine) is described, thereby offering new opportunities in the synthesis of nonracemic beta-diketimine- and pyridine-based chiral catalysts.

Screening of pi-basic naphthalene and anthracene amplifiers for pi-acidic synthetic pore sensors.

Synthetic ion channels and pores attract current attention as multicomponent sensors in complex matrixes. This application requires the availability of reactive signal amplifiers that covalently capture analytes and drag them into the pore. pi-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers because aromatic electron donor-acceptor (AEDA) interactions account for their recognition within pi-acidic naphthalenediimide (NDI) rich synthetic pores. Focusing on amplifier design, we report here the synthesis of a complete collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation potentials by cyclic voltammetry, and calculate their quadrupole moments. Blockage experiments reveal that subtle structural changes in regioisomeric DAN amplifiers can be registered within NDI pores. Frontier orbital overlap in AEDA complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are shown to contribute to isomer recognition by synthetic pores. Particularly important with regard to practical applications of synthetic pores as multianalyte sensors, we further demonstrate that application of the lessons learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides access to privileged amplifiers with submicromolar activity.

Synthetic and isolation studies related to the marine natural products (+)-elisabethadione and (+)-elisabethamine.

These studies were conducted to determine the discrepancies between the spectroscopic data of the isolated and synthetic samples of the marine natural product (+)-elisabethadione. Attempts at the re-isolation of (+)-elisabethadione from Pseudopterogorgia elisabethae were unsuccessful, but during these efforts, two related natural products of O-methylelisabethadione (8) and O-methyl-nor-elisabethadione (9) were discovered. The total syntheses of these new natural products were accomplished by using the combined C-H activation/Cope rearrangement as the key step and the previously synthesized elisabethadione was converted to O-methylelisabethadione. These studies confirmed that the synthetic sample of (+)-elisabthadione was assigned the correct structure. The considerable differences in the data between the synthetic and natural samples of (+)-elisabethadione lead to the conclusion that the structure of the natural material was either miss-assigned or the published spectral data were incorrect. During the course of these studies, questions arose about the assigned structure of another natural product, elisabethamine, which was proposed to be an aminohydroquinone. Attempts at the synthesis of this compound revealed that the aminohydroquinone structure was unstable in air as it was readily oxidized to the quinone.