Naphthalimide Moiety Research Articles

Development of Unsymmetrical Dyads As Potent Noncarbohydrate-Based Inhibitors against Human β-N-Acetyl-d-hexosaminidase.

Human β-N-acetyl-d-hexosaminidase has gained much attention due to its roles in several pathological processes and been considered as potential targets for disease therapy. A novel and efficient skeleton, which was an unsymmetrical dyad containing naphthalimide and methoxyphenyl moieties with an alkylamine spacer linkage as a noncarbohydrate-based inhibitor, was synthesized, and the activities were valuated against human β-N-acetyl-d-hexosaminidase. The most potent inhibitor exhibits high inhibitory activity with K i values of 0.63 μM. The straightforward synthetic manners of these unsymmetrical dyads and understanding of the binding model could be advantageous for further structure optimization and development of new therapeutic agents for Hex-related diseases.

Synthesis, physiochemical and optical properties of chitosan based dye containing naphthalimide group

A new biopolymer dye containing naphthalimide moiety was synthesized by reaction of N-naphthaloyl chitosan with 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazino-3-quinolinecarboxylic acid. N-naphthaloyl chitosan was synthesized by reaction of chitosan with 4-bromo-1,8-naphthalic anhydride in aqueous media by greener approach. The degree of substitution of chitosan biopolymer dye is 0.55 with a yield of 70%. The synthesized materials were characterized by using UV–vis, 1H NMR, FTIR, and FT-Raman spectroscopy. Some physical properties and surface morphology were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Optical properties of chitosan biopolymer dye were evaluated by photoluminescence (PL) spectroscopy that showed red shift (λem) peak at 442nm and 551nm at excitation wavelength 325nm in comparison to chitosan. The solubility of chitosan biopolymer dye increased in most of the organic solvents. These results may provide new perspectives in biomedical applications as an optical and sensitive biosensor material.

Exciton coupling in molecular salts of 2-(1,8-naphthalimido)ethanoic acid and cyclic amines: modulation of the solid-state luminescence

In this study we have purposely altered the solid state luminescence properties of 2-(1,8-naphthalimido)ethanoic acid (NEaH) (0) via molecular salts formation with cyclic amines such as 1,4-diazabicyclo[2.2.2]octane (DABCO), quinuclidine (ABCO), 3-quinuclidinol (OH-ABCO), and piperazine (PIP). All crystalline materials have been characterized in the solid state via single-crystal and variable temperature powder X-ray diffraction and thermal methods; luminescence spectra in the solid state have been recorded. Exciton interactions have been determined with quantum-chemical calculations for all molecular organic salts, and tuning of their magnitude in response to changes in the crystal packing has been demonstrated. It is suggested that the variations in photoluminescence can be interpreted on the basis of the different excitonic interactions amongst the naphthalimide moieties.

Preparation of low toxic fluorescent chitosan-graft-polyethyleneimine copolymer for gene carrier

Fluorescent chitosan-graft-polyethyleneimine (PEI) copolymer was prepared by incorporating PEI molecule onto chitosan backbone through naphthalimide moiety by simple substitution reaction. 4-Bromo-1,8-naphthalic anhydride was used as fluorescent probe due to its strong fluorescence and good photo-stability property and the presence of a fine tunable bromide functional group in the naphthalimide ring, in this work. The copolymer was characterized by FTIR, elemental analysis and XRD. The fluorescence property of the copolymer was determined by UV–vis spectrometer and spectrofluorometer. The effects of pH and temperature on fluorescence property of the copolymer were also studied. The graft copolymer with degree of substitution 37.6 of PEI onto chitosan showed better complexation ability with DNA at comparatively low N/P (nitrogen to phosphate ratio) ratio 1.0 compared to that of chitosan (N/P ratio 2.0). The cytotoxicity of PEI largely decreased after grafting with chitosan and all the copolymers showed above 50% cell viability even at high polymer concentration (300μg/mL). Therefore, the prepared fluorescent chitosan-graft-PEI copolymer may be used as a biological marker as well as drug or gene carrier with low toxicity.

Ion Interactions with a New Ditopic Naphthalimide‐Based Receptor: A Photophysical, NMR and Theoretical (DFT) Study

A new multi-component chemosensor system comprising a naphthalimide moiety as fluorophore is designed and developed to investigate receptor-analyte binding interactions in the presence of metal and non-metal ions. A dimethylamino moiety is utilized as receptor for metal ions and a thiourea receptor, having acidic protons, for binding anions. The system is characterized by conventional analytical methods. The absorption and fluorescence spectra of the system consist of a broad band typical for an intramolecular charge transfer (ICT). The effects of various metal-ion additives on the spectral behavior of the present sensor system are examined in acetonitrile. It is found that among the metal ions studied, alkali/alkaline earth-metal ions and transition-metal ions modulate the absorption and fluorescence spectra of the system. As an additional feature, the anion signaling behavior of the system in acetonitrile is studied. A decrease in fluorescence efficiency of the system is observed upon addition of fluoride and acetate anions. Fluorescence quenching is most effective in the case of fluoride ions. This is attributed to the enhancement of the photoinduced electron transfer from the anion receptor to the fluorophore moiety. Hydrogen-bond interactions between the acidic NH protons of the thiourea moiety and the F(-) anions are primarily attributed to the fluoride-selective signaling behavior. Interestingly, a negative cooperativity for the binding event is observed when the interactions of the system are studied in the presence of both Zn(2+) and F(-) ions. NMR spectroscopy and theoretical calculations are also carried out to better understand the receptor-analyte binding.

Detection of Zn2+ ion on a reusable fluorescent mesoporous silica beads in aqueous medium

An efficient sensor system was designed and built by immobilizing a fluorescent bischromophoric dyad through a sol–gel reaction on mesoporous silica beads of high surface area. The silica supported dyad, SSD containing anthracene and naphthalimide moieties have shown high sensitivity and selectivity to detect Zn2+ among the tested cations in aqueous medium. The Job’s plot analysis showed a 1:1 stoichiometry for a complexation between SSD and Zn2+ in which the relative fluorescence intensity enhanced, ~6 times due to restricted photoinduced electron transfer reaction and color of the beads were changed from a fluorescent yellow green to blue. The reversible mode of complexation was tested in the presence of EDTA.

Selective modification of layered silicate nanoparticle edges with fluorophores

The modification of two synthetic layered silicates, fluorohectorite (Corning) and laponite (Laporte), with two reactive silanes functionalized with fluorescent rhodamine or naphthalimide led to the grafting of the silicate particles selectively at the particle edges. The small amounts of grafted silanes were neither detected by infrared spectra nor X-ray diffraction (XRD) patterns. The larger extent of modification with cationic rhodamine-based silane was detected by XRD. The absorption and fluorescence spectra of the colloids of grafted silicates were similar to those of silane-dye precursors. Confocal fluorescence microscopy and fluorescence lifetime imaging detected the fluorohectorite-naphthalimide monolayer films to be optically heterogeneous, which was attributed to the selective location of the bound naphthalimide moieties at the particle edges.

White Fluorescence from Core–Shell Silica Nanoparticles

Into the white: Encapsulation of a naphthalimide moiety in the core of silica nanoparticles afforded nanospheres with a strong green excimeric emission. Together with the blue emission of the monomeric naphthalimide and the yellow fluorescence of the tetrazine acceptor on the outer shell, the added contributions provide intense white fluorescence upon 330 nm UV excitation.

New Application of Proton Nuclear Spin Relaxation Unraveling the Intermolecular Structural Features of Low-Molecular-Weight Organogel Fibers

Proton nuclear spin relaxation has been for the first time extensively used for a structural and dynamical study of low-molecular-weight organogels. The gelator in the present study is a modified phenylalanine amino acid bearing a naphthalimide moiety. From T(1) (spin-lattice relaxation time in the laboratory frame) and T(1ρ) (spin-lattice relaxation time in the rotating frame) measurements, it is shown that the visible gelator NMR spectrum below the liquid-gel transition temperature corresponds to a so-called isotropic compartment, where gelator molecules behave as in a liquid phase but exchange rapidly with the molecules constituting the gel structure. This feature allows one to derive, from accessible parameters, information about the gel itself. Nuclear Overhauser effect spectroscopy (NOESY) experiments have been exploited in view of determining not only cross-relaxation rates but also specific longitudinal rates. The whole set of relaxation parameters (at 25 °C) leads to a correlation time of 5 ns for gelator molecules within the gel structure and 150 ps for gelator molecules in the isotropic phase. This confirms, on one hand, the flexibility of the organogel fibers and, on the other hand, the likely presence of clusters in the isotropic phase. Concerning cross-relaxation rates, a thorough theoretical investigation in multispin systems of direct and relayed correlations in a NOESY spectrum allows one to make conclusions about contacts (around 2-3 Å) not only between naphtalimide moieties of different gelator molecules but also between the phenyl ring and the naphtalimide moiety again of different gelator molecules. As a result, not only is the head-to-tail structure of amino acid columns confirmed but also the entangling of nearby columns by the naphthalimide moieties is demonstrated.

Direct Fluorescence Monitoring of the Delivery and Cellular Uptake of a Cancer-Targeted RGD Peptide-Appended Naphthalimide Theragnostic Prodrug

Presented here is a multicomponent synthetic strategy that allows for the direct, fluorescence-based monitoring of the targeted cellular uptake and release of a conjugated therapeutic agent. Specifically, we report here the design, synthesis, spectroscopic characterization, and preliminary in vitro biological evaluation of a RGD peptide-appended naphthalimide pro-CPT (compound 1). Compound 1 is a multifunctional molecule composed of a disulfide bond as a cleavable linker, a naphthalimide moiety as a fluorescent reporter, an RGD cyclic peptide as a cancer-targeting unit, and camptothecin (CPT) as a model active agent. Upon reaction with free thiols in aqueous media at pH 7.4, disulfide cleavage occurs. This leads to release of the free CPT active agent, as well as the production of a red-shifted fluorescence emission (λ(max) = 535 nm). Confocal microscopic experiments reveal that 1 is preferentially taken up by U87 cells over C6 cells. On the basis of competition experiments involving okadaic acid, an inhibitor of endocytosis, it is concluded that uptake takes place via RGD-dependent endocytosis mechanisms. In U87 cells, the active CPT payload is released within the endoplasmic reticulum, as inferred from fluorescence-based colocalization studies using a known endoplasmic reticulum-selective dye. The present drug delivery system (DDS) could represent a new approach to so-called theragnostic agent development, wherein both a therapeutic effect and drug uptake-related imaging information are produced and can be readily monitored at the subcellular level. In due course, the strategy embodied in conjugate 1 could allow for more precise monitoring of dosage levels, as well as an improved understanding of cellular uptake and release mechanisms.

Synthesis and Photophysical Behavior of Two Novel Bis(1,8-naphthalimides) Containing Triazine Spacers

以1,8-萘酰亚胺和三聚氯氰为主要原料, 合成了两种由三嗪环桥连的双1,8-萘酰亚胺化合物3 和5. 采用紫外-可见光谱和荧光光谱等手段考察了两种化合物在不同溶剂中的光物理行为. 与参比化合物N-丁基-1,8-萘酰亚胺相比, 在二氯甲烷、三氯甲烷和甲醇等极性溶剂中, 化合物3和5除了在短波区（λ〈400 nm）存在1,8-萘酰亚胺的特征荧光发射峰外, 在长波区（〉450 nm）均产生一个较强的新荧光发射峰, 表现出分子内激基缔合物的光物理行为. 与化合物5相比, 由于化合物3特殊的构象异构, 其荧光强度发生严重的猝灭. 在非极性溶剂甲基环己烷中, 化合物5 由于存在较强的分子间氢键作用而聚集, 受激后形成了较稳定的分子间激基缔合物, 但未观察到明显的分子内激基缔合物的形成. 在甲苯溶剂中, 化合物3和5与甲苯分子形成了激基复合物, 并未形成分子内激基缔合物. 进一步研究3和5的固态激发态性质, 发现化合物3和5的固体薄膜受激后分别在465和469 nm处出现激基缔合物的特征荧光发射峰.

A new N-imidazolyl-1,8-naphthalimide based fluorescence sensor for fluoride detection

A chemosensor is reported with high sensitivity and selectivity for detection of fluoride anion. The recognition mechanism is attributed to a fluoride-triggered disruption of the hydrogen bond between imidazole and naphthalimide moieties, resulting in a noncoplanar geometry with low fluorescence.

Synthesis and Photochromism of Naphthopyrans Bearing Naphthalimide Chromophore: Predominant Thermal Reversibility in Color-Fading and Fluorescence Switch

Two novel photochromic naphthopyrans containing naphthalimide moieties (Nip1 and Nip2) were studied in solution under flash photolysis conditions, exhibiting highly photochromic response, rapid thermal bleaching rate and good fatigue-resistance. Owing to the different N-substituted imide groups at the naphthalimide units, the thermal bleaching rate of Nip2 bearing phenyl on the naphthalimide unit is found to be approximately 2 times that of Nip1 bearing n-butyl, indicating that the photochromic properties can be modulated with introduction of different functional groups on the naphthalimide unit. In Nip1 and Nip2, the strong electron-withdrawing effect of the imide group incorporated at the naphthalimide moiety maintains several merits: (i) shifting absorption bands to longer wavelength, (ii) beneficial to an enhancement in the ratio of transoid-cis (TC) isomer and an increase in the transformation rate from transoid-trans (TT) to TC with respect to reference compound NP, and (iii) resulting in a preferable color bleaching rate and fading absolutely to their colorless state with thermal reversibility. As demonstrated in the system of NP, the slow transformation process from TT to TC might be the predominant dynamic step in thermal back process, leading to the residual color of NP being only faded to its original colorless state by visible light irradiation. The optical densities of colored forms for Nip1 and Nip2 are dependent upon the intensity of incident light, ensuring a possible application in the manufacture of ophthalmic lenses and smart windows. Moreover, the fluorescence of Nip1 and Nip2 can be switched on and off by photoinduced conversion between the closed and open forms.

Long-Lived Room Temperature Deep-Red/Near-IR Emissive Intraligand Triplet Excited State (3IL) of Naphthalimide in Cyclometalated Platinum(II) Complexes and Its Application in Upconversion

[C(^)NPt(acac)] (C(^)N = cyclometalating ligand; acac = acetylacetonato) complexes in which the naphthalimide (NI) moiety is directly cyclometalated (NI as the C donor of the C-Pt bond) were synthesized. With 4-pyrazolylnaphthalimide, isomers with five-membered (Pt-2) and six-membered (Pt-3) chelate rings were obtained. With 4-pyridinylnaphthalimide, only the complex with a five-membered chelate ring (Pt-4) was isolated. A model complex with 1-phenylpyrazole as the C(^)N ligand was prepared (Pt-1). Strong absorption of visible light (ε = 21,900 M(-1) cm(-1) at 443 nm for Pt-3) and room temperature (RT) phosphorescence at 630 nm (Pt-2 and Pt-3) or 674 nm (Pt-4) were observed. Long-lived phosphorescences were observed for Pt-2 (τ(P) = 12.8 μs) and Pt-3 (τ(P) = 61.9 μs). Pt-1 is nonphosphorescent at RT in solution because of the acac-localized T(1) excited state [based on density functional theory (DFT) calculations and spin density analysis], but a structured emission band centered at 415 nm was observed at 77 K. Time-resolved transient absorption spectra and spin density analysis indicated a NI-localized intraligand triplet excited state ((3)IL) for complexes Pt-2, Pt-3, and Pt-4. DFT calculations on the transient absorption spectra (T(1) → T(n) transitions, n > 1) also support the (3)IL assignment of the T(1) excited states of Pt-2, Pt-3, and Pt-4. The complexes were used as triplet sensitizers for triplet-triplet-annihilation (TTA) based upconversion, and the results show that Pt-3 is an efficient sensitizer with an upconversion quantum yield of up to 14.1%, despite its low phosphorescence quantum yield of 5.2%. Thus, we propose that the sensitizer molecules at the triplet excited state that are otherwise nonphosphorescent were involved in the TTA upconversion process, indicating that weakly phosphorescent or nonphosphorescent transition-metal complexes can be used as triplet sensitizers for TTA upconversion.

A naphthalimide–rhodamine ratiometric fluorescent probe for Hg 2+ based on fluorescence resonance energy transfer

On the basis of fluorescent resonance energy transfer from 1,8-naphthalimide to rhodamine B, a new fluorophore dyads ( 4) containing rhodamine B and a naphthalimide moiety was synthesized as a ratiometric fluorescent probe for detecting Hg 2+ with a broad pH range 5.7–11.0. The selective fluorescence response of 4 to Hg 2+ is due to the Hg 2+-promoted desulfurization of the thiocarbonyl moiety, leading to the ring-opening of rhodamine B moiety of 4. When 4 was employed at 0.1 μM with the slit size being 20 nm/20 nm, a low level of Hg 2+ (up to 3 × 10 −8 M) can be detected using the system.

Recognition of Polycyclic Aromatic Hydrocarbons and Their Derivatives by the 1,3-Dinaphthalimide Conjugate of Calix[4]arene: Emission, Absorption, Crystal Structures, and Computational Studies

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants as well as well-known carcinogens. Therefore, it is important to develop an effective receptor for the detection and quantification of such molecules in solution. In view of this, a 1,3-dinaphthalimide derivative of calix[4]arene (L) has been synthesized and characterized, and the structure has been established by single crystal XRD. In the crystal lattice, intermolecular arm-to-arm π···π overlap dominates and thus L becomes a promising receptor for providing interactions with the aromatic species in solution, which can be monitored by following the changes that occur in its fluorescence and absorption spectra. On the basis of the solution studies carried out with about 17 derivatives of the aromatic guest molecular systems, it may be concluded that the changes that occur in the fluorescence intensity seem to be proportional to the number of aromatic rings present and thus proportional to the extent of π···π interaction present between the naphthalimide moieties and the aromatic portion of the guest molecule. Though the nonaromatic portion of the guest species affects the fluorescence quenching, the trend is still based on the number of rings present in these. Four guest aldehydes are bound to L with K(ass) of 2000-6000 M(-1) and their minimum detection limit is in the range of 8-35 μM. The crystal structure of a naphthaldehyde complex, L.2b, exhibits intermolecular arm-to-arm as well as arm-to-naphthaldehyde π···π interactions. Molecular dynamics studies of L carried out in the presence of aromatic aldehydes under vacuum as well as in acetonitrile resulted in exhibiting interactions observed in the solid state and hence the changes observed in the fluorescence and absorption spectra are attributable for such interactions. Complex formation has also been delineated through ESI MS studies. Thus L is a promising receptor that can recognize PAHs by providing spectral changes proportional to the aromatic conjugation of the guest and the extent of aromatic π···π interactions present between L and the guest.

Novel dyes based on naphthalimide moiety as electron acceptor for efficient dye-sensitized solar cells

Four novel naphthalimide-based dyes (D-1, D-2, D-3 and D-4) were synthesized and utilized as sensitizers in dye-sensitized solar cells (DSCs), in which the triphenylamine (TPA) or indoline groups, naphthalimide unit and carboxylic group were functionalized as electron donor, acceptor and anchoring group, respectively. The naphthalimide unit was employed as the π-conjugation ring and electron acceptor for effectively realizing intramolecular charge separation in the oxidized states. In the series of dyes, the LUMO orbital is delocalized mainly on naphthalimide moieties, especially on the carbonyl group. Consequently, the LUMO electrons are isolated from the carboxyl anchoring group (-CH 2CO 2H) due to the presence of the methylene group, which could suppress the electron injection efficiency from the excited dyes to the TiO 2 conduction band, thus leading to the inferior efficiencies of 1.10, 1.18, 2.27 and 2.70%, respectively, even though they exhibit broad spectral response and high extinction coefficients.

Synthesis and Photophysical Characterizations of Thermal -Stable Naphthalene Benzimidazoles

Microwave-assisted synthesis, photophysical and electrochemical properties of thermal-stable naphthalene benzimidazoles and naphthalimides are studied in this paper. Microwave-assisted synthesis of naphthalene benzimidazoles provide higher yields than the conventional thermal synthesis. Comparative photophysical properties of naphthalene benzimidazoles and naphthalimides are revealed that conjugation of electron-donating group onto naphthalimide moiety increases fluorescence quantum yields. Fluorophore-solvent interactions are also investigated using Lippert-Mataga equation for naphthalimides and naphthalene benzimidazoles. Thermal stabilities of naphthalene benzimidazoles are better than naphthalimides due to increased aromaticity. The experimental E(LUMO) levels of naphthalene benzimidazoles are found to be between 3.15 and 3.28 eV. Therefore, naphthalene benzimidazole derivatives consisting of anchoring groups are promising materials in organic dye sensitized solar cells.

Abstract 742: Development of novel naphthalimide derivatives as potential melanoma therapeutics

Abstract Over the years, several naphthalimide analogs with varying efficacy have been reported as having promising anti-cancer properties. Some analogs such as mitonafide, a tolemerase inhibitor, have shown an interesting antitumor activity both preclinically and in phase I and phase II clinical trials. However, it suffers from severe toxicity issues, especially central nervous system (CNS) toxicity. Because of toxicity issues, mitonafide could only be delivered by i.v. infusion, and still CNS toxicity is a major issue. This problem was overcome by adapting a delivery strategy of 5 days continuous infusion, but this regimen was not effective in NSCLC or colorectal cancer patients, while still having severe myelotoxicity in the latter case. These observations warranted optimization of mitonafide structure by adding appropriate functional groups that could help reduce systemic toxicity, while keeping the key naphthalimide moiety intact. We hypothesized that incorporation of functional groups such as isothiocyanate group which is present various naturally occurring agents found in cruciferous vegetables would enhance the bioavailability and reduce systemic toxicity levels. By analogy, isoselenocyanate group which has recently been shown by us to follow a similar mechanism with enhanced potency was also introduced. Furthermore, we also synthesized a series of mitonafide analogs with functional alterations such as thiourea and selenourea in place of N,N-dimethyl functionality in mitonafide, with or without nitro substitution. Interestingly, all the sulfur analogs [IC50 (72 h): 2-9 uM] were more cytotoxic than their corresponding selenium derivatives [IC50 (72 h): 11-24 uM], as observed by the MTS assay in various human melanoma cell lines. This was in sharp contrast to our earlier studies, where isosteric selenium analogs were more effective in killing multiple cancer cells and about 3 times more effective in inhibiting melanoma tumor development. Furthermore, the sulfur analogs effectively induced apoptosis in UACC 903 human melanoma cells. Nitro substitution or increase in alkyl chain length did not seem to make any significant difference in the activity of these compounds. Though the IC50 values were 2-4 times lower for mitonafide [IC50 (72 h): 1-2 uM] compared to novel isothiocyante or thiourea derivatives, these new derivatives were well tolerated when injected i.p. in mice everyday for a month. The new naphthalimide derivatives thus hold solid promise as melanoma therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 742.

Hyperbranched polyyne containing naphthalimide moiety as a fluorescent chemosensor for mercury ion

The development of multidimentional conjugated polymers as fluorescent sensor has been extremely attractive for detecting toxic ion in trace level. In this paper, a new hyperbranched polyyne with polytris(4-ethynylphenyl) amine (PTEPA) as the core, benzoyl thiourea-naphthalimide (NAP) as Hg (II) detected unit was designed and synthesized. The addition of Hg (II) ion transforms the thiourea unit of the chemodosimeter under THF conditions into an imidazoline moiety that is a much less electron-donating group, and hence results in a reduction in electron delocalization within the fluorophore. The emission maximum exhibits blue-shift and increase of fluorescent intensity. To confirm selectivity of the sensor towards mercury ions, it was also titrated with other divalent metal ions. No significant change was observed in the fluorescence spectra.