Anthracene Conjugates Research Articles

L-tryptophan-assisted anthracene functionalization for copper-induced fluorescence Turn-off and controlled supramolecular nano-assembly

A fluorescent chemosensor, l-Tryptophan-assisted Anthracene conjugate (1), has been designed and developed. 1 is highly selective and sensitive for detecting Cu(II) ions through a fluorescence "turn-off" mechanism, even in a competing environment with a high detection limit of 9.4 × 10−6 M. The smaller spherical nano-assembly transforms into larger spherical nano-assembly upon incubation with Cu(II) ions, highlighting the metal-induced morphological transformation of nano-assemblies.

Multifarious Impact of Rhodanine Acceptor Group on the Optical Properties of Some Semiconductor Probes

AbstractSteady state optical properties such as photo‐absorption and photo‐luminescence characteristics of organic molecules in its bulk states viz, film or crystalline forms are highly sensitive to subtle alteration of chemical substitution, molecular geometry in bulk and the electronic state coupling between a pair of molecules. Here we highlight a distinct interference of rhodanine substitution on such optical properties of a group of similar molecules (2TR, 23TR). For comparison an anthracene conjugate model molecule was also chosen (AR). In the former case, despite of having similar molecular structure except the presence of a methyl group at the C3 position (which ensures the identical electronic states in both the case) and similar molecular packing in single crystals, 2TR and 23TR exhibited diagonally opposite solid‐state fluorescence behavior. 2TR was non‐fluorescent whereas, 23TR was highly emissive in its crystalline solid state. A minute substitutional change in chemical structure was found to alter the solid‐state fluorescence behavior immensely that was attributed to the non‐radiative loss in the former case due to the solid‐state C−C bond flip which was further proven by temperature dependent fluorescence experiments. At a sample temperature of <120 K, 20‐fold enhancement in the fluorescence intensity was observed.

Discrete π Stack of a Tweezer-Shaped Naphthalenediimide-Anthracene Conjugate.

The design and synthesis of a tweezer-shaped naphthalenediimide (NDI)-anthracene conjugate (2NDI) are reported. In the structure of the closed form (πNDI ⋅⋅⋅πNDI stack) of 2NDI, which was elucidated by single-crystal XRD, the existence of C-H⋅⋅⋅O hydrogen bonding involving the nearest carbonyl oxygen atom of an NDI unit was suggested. The tunability of πNDI ⋅⋅⋅πNDI interactions was studied by means of UV/Vis absorption, fluorescence and NMR spectroscopy and molecular modelling. This revealed that the πNDI ⋅⋅⋅πNDI interactions in 2NDI affect the absorption and emission properties depending on the temperature. Furthermore, in polar solvents, 2NDI prefers the stronger πNDI ⋅⋅⋅πNDI stack, whereas the πNDI ⋅⋅⋅πNDI interaction is diminished in nonpolar solvents. Importantly, the conformational variations of 2NDI can be reversibly switched by variation in temperature, and this suggests potential application for fluorogenic molecular switches upon temperature changes.

Synthesis of Anthracene Conjugates of Truncated Antifreeze Protein Sequences: Effect of the End Group and Photocontrolled Dimerization on Ice Recrystallization Inhibition Activity.

Biomacromolecular antifreezes distinguish ice from water, function by binding to specific planes of ice, and could have many applications from cryobiology to aerospace where ice is a problem. In biology, antifreeze protein (AFP) activity is regulated by protein expression levels via temperature and light-regulated expression systems, but in the laboratory (or applications), the antifreeze activity is "always on" without any spatial or temporal control, and hence methods to enable this switching represent an exciting synthetic challenge. Introduction of an abiotic functionality into short peptides (e.g., from solid-phase synthesis) to enable switching is also desirable rather than on full-length recombinant proteins. Here, truncated peptide sequences based on the consensus repeat sequence from type-I AFPs (TAANAAAAAAA) were conjugated to an anthracene unit to explore their photocontrolled dimerization. Optimization of the synthesis to ensure solubility of the hydrophobic peptide included the addition of a dilysine solubilizing linker. It was shown that UV-light exposure triggered reversible dimerization of the AFP sequence, leading to an increase in molecular weight. Assessment of the ice recrystallization inhibition activity of the peptides before and after dimerization revealed only small effects on activity. However, it is reported here for the first time that addition of the anthracene unit to a 22-amino-acid truncated peptide significantly enhanced ice recrystallization inhibition compared to the free peptide, suggesting an accessible synthetic route to allow AFP activity using shorter, synthetically accessible peptides with a photoreactive functionality.

G-Quadruplex-Specific Cell-Permeable Guanosine-Anthracene Conjugate Inhibits Telomere Elongation and Induces Apoptosis by Repressing the c-MYC Gene.

We herein report a cell-membrane-permeable molecular probe ADG, prepared by conjugating guanosine with anthracene, selectively interacts with c-MYC G-quadruplex over other promoter and telomeric quadruplexes as well as duplex DNA. NMR spectroscopy suggests that ADG interacts with terminal G-quartets as well as with the nearby G-rich tract (G13-G14-G15 and G8-G9-G10) of c-MYC quadruplex. In vitro cellular studies indicate that ADG represses c-MYC expression by stabilizing its promoter G-quadruplex and alters c-MYC-related cellular events. ADG suppresses hTERT and BCL2 gene expressions in a promoter-independent manner, inhibits elongation of telomere length, and activates apoptotic cascades in cancer cells.

Kinetics of singlet oxygen sensing using 9-substituted anthracene derivatives$$^{\#}$$

Singlet oxygen ( $$^{1}\hbox {O}_{2}$$ ), the lowest excited-state of molecular oxygen receives great attention in basic research and clinical and industrial settings. Despite several spectroscopic methods available for $$^{1}\hbox {O}_{2}$$ sensing, fluorescence sensing receives great attention, for which many fluorogenic sensors based on substituted anthracene are reported. Nonetheless, the roles of substituents on the sensing efficiency, in terms of detection time, remain largely unknown. In this work, we examine the $$^{1}\hbox {O}_{2}$$ sensing efficiency of a fluorescence sensor based on a coumarin–anthracene conjugate, which is an electron donor-acceptor dyad, and compare the efficiency with that of 9-methylanthracene. Here, $$^{1}\hbox {O}_{2}$$ is generated using the standard photosensitizer Rose Bengal, which is followed by estimation of the rate of reaction of $$^{1}\hbox {O}_{2}$$ to the sensor and 9-methylanthracene. The second order reaction rate of the sensor is an order of magnitude less than that of 9-methylanthracene. The lower reactivity of the sensor to $$^{1}\hbox {O}_{2}$$ suggests that the roles of substituents, such as electronic interactions, steric interactions and the reactivity of precursor complexes, on sensing efficiency should be carefully considered during construction of fluorogenic molecular sensors. SYNOPSIS The kinetics of singlet oxygen sensing using a 9-substituted anthracene derivative is studied by comparing the photooxidation rates of a conjugate between 9-methyl anthracene and a coumarin dye. The singlet oxygen sensing rate points out that the electronic interaction and steric effect induced by the substituents on anthracene influence the kinetics of sensing.

Fullerene-Based n-Type Materials That Can Be Processed by a Photoprecursor Approach for Photovoltaic Applications

The active layer of organic photovoltaic cells (OPVs) is typically a blend of p- and n-type semiconductors, and the arrangement of these materials largely affects the device performance. We have recently proposed a unique deposition technique in which α-diketone-type photoprecursors are solution-deposited and then subjected to in-situ photoreaction to form acene-based semiconductors, as an effective means for controlling the morphology and vertical composition profile in organic molecular blends. However, the applicability of this “photoprecursor approach” has been limited to p-type materials so far, restricting the flexibility in designing photovoltaic layers. Herein, we report α-diketone-type photoprecursors of two fullerene–anthracene conjugates which have been designed to serve as n-type material in OPVs. The new α-diketones, named N601DK and N602DK, are successfully applied to the photoprecursor approach, affording smooth thin films of the corresponding photoreaction products N601 and N602. The n-type materials thus produced are evaluated in bulk-heterojunction (BHJ) OPVs and found to show good photovoltaic response. Especially, N601 performs as well as PC61BM, a fullerene-based benchmark n-type material. These results will serve as a basis for further improvement of OPVs through optimization of the molecular arrangement in solution-processed photovoltaic layers.

P0200 Use of polyamine transport system by polyamine anthracene conjugates in human leukaemic cells

Background It is well known that cancer cells have increased polyamine concentrations compared with normal cells. This relation is due to a combination of increased polyamine uptake via the polyamine transport system (PTS) as well as increased biosynthesis. Thus, we may be able to exploit the PTS for selective delivery of cytotoxic agents to cancer cells by attaching them to polyamine vectors. Such an approach should reduce non-specific toxicities and therefore decrease the side-effects associated with chemotherapy. This concept is also supported by the nature of PTS, which can accommodate a wide range of substrates. Three compounds combining the DNA intercalator, anthracene, with a polyamine side chain have been synthesised: Ant 4, Ant 44, and Ant 444.The aim of this study was to investigate the mode of cell death induced by anthracene conjugates in HL-60 cell lines. Methods We used a variety of techniques to study the response of HL-60 cells to Ant 4, Ant 44, and Ant 444. Findings Deconvolution microscopy analysis revealed that the conjugates entered the cells. Quantitative analysis using high-performance liquid chromatography showed that the amount of Ant 4 in cells increased 30% from 6 h to 12 h. Ant 44 showed the highest level in cells after 6 h of exposure. Ant 444 showed a gradual increase between 0 h to 48 h. The indirect evidence using pre-treated cells with 5 mmol difluromethylornithine (DFMO) showed a significant decrease of IC 50 compared with no DFMO pretreatment for Ant 4, Ant 44, and Ant 444. The uptake study using radiolabelled polyamines showed there is a competition uptake between radiolabelled polyamines [ 14 C] putrescine, spermidine, or spermine with Ant 4, Ant 44, and Ant 444. Interpretation Ant 4, Ant 44, and Ant 444 gain entry into HL-60 cells via the PTS. The idea of selectively targeting cancer cells via the PTS shows promise. In the future, the concept of selective targeting of cancer cells via the PTS could lead to the development of novel and effective anticancer therapies.

Sensitive and Selective Redox, Chromogenic, and “Turn-On” Fluorescent Probe for Pb(II) in Aqueous Environment

The electrochemical, optical, and metal cation sensing properties of the triazole-tethered ferrocene-anthracene conjugates, C(48)H(40)FeO(2)N(6) (3) and C(52)H(40)FeO(2)N(6) (4), and the ferrocene-pyrene conjugates, C(29)H(25)FeON(3) (5) and C(31)H(25)FeON(3) (6), have been documented. All the compounds 3-6 behave as very selective redox, chromogenic, and "turn-on" fluorescent probes for Pb(2+) ion in an aqueous environment (CH(3)CN/H(2)O, 2/8). The significant changes in their absorption spectra are accompanied by a strong color change from yellow to greenish blue, which allows a prospective use for the "naked eye" detection of Pb(2+) ion over other competitor cations such as Hg(2+) and Cd(2+). These chemosensors present immense brightness and fluorescence enhancement (chelation-enhanced fluorescence = 85 for 3 and 92 for 4) following Pb(2+) coordination within the limit of detection at 2 ppb. Interestingly, their fluorescence, redox, and colorimetric responses are preserved in presence of water, which can be used for the selective colorimetric detection of Pb(2+) ion in aqueous environment over Hg(2+) and Cd(2+) cations. All the compounds have been characterized by (1)H, (13)C NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) spectrometric analysis, and the solid-state structures of 5 and 6 have been unequivocally established by X-ray diffraction analysis.

A fluorescent probe for the selective detection of sulfate ions in water

A nicotinamide–anthracene conjugate based fluorescent probe 1 exhibits highly selective fluorescence enhancement at 535 nm only with sulfate in HEPES buffer–DMSO (9:1) at pH 7.4. The other anions viz. F−, Cl−, Br−, I−, AcO−, HSO4−, H2PO4−, CN−, OH−, NO3−, ClO4−, SCN−, even if present in excess, do not interfere in the estimation of sulfate. The limit of detection for sulfate ions by probe 1 is 0.5 μM. Probe 1 can also be used to determine the sulfate ions in tap water using EDTA as a metal ion masking agent. Titration experiments and Job's plot reveal the formation of a 1:1 stoichiometric complex between the probe 1 and sulfate ions and DFT studies show the electron transfer from SO42− to anthracene moiety responsible for the observed optical changes.

Charge-transfer interaction mediated organogels from bile acid appended anthracenes: rheological and microscopic studies

In this article we present dual-component charge-transfer interaction (CT) induced organogel formation with bile acid anthracene conjugates as donors and 2,4,7-trinitrofluorenone (TNF) as the acceptor. The use of TNF (1) as a versatile electron acceptor in the formation of gels is demonstrated through the formation of gels with different steroidal groups on the anthracene moiety in a variety of solvents ranging from aromatic hydrocarbons to long chain alcohols. Thermal stability and variable temperature fluorescence experiments were performed on these CT gels. Dynamic rheological experiments conducted on these gels suggest that these are viscoelastic soft materials and with the gel strength can be modulated by varying the donor/acceptor ratios.

Polyamine–anthracene conjugates show promise in delivery of cytotoxic agents to human solid tumour cells

Polyamine–anthracene conjugates show promise in delivery of cytotoxic agents to human solid tumour cells

Synthesis of covalently linked boron–dipyrromethene–chromophore conjugates using 3-bromo boron–dipyrromethene as a key precursor

3-Bromo boron dipyrromethene (3-bromo BODIPY) has been used as key synthon to prepare one ethynyl bridged and six ethynylphenyl bridged BODIPY–chromophore conjugates using mild Pd(0) coupling conditions. The chromophores possessing very distinct features, such as anthracene, BODIPY, terpyridine, porphyrin, Zn(II)porphyrin, 21,23-dithiaporphyrin and thiasapphyrin were connected at 3-position of boronboron–dipyrromethene dye by coupling of 3-bromo BODIPY with ethynyl or ethynylphenyl chromophore in toluene/triethylamine in the presence of catalytic amount of AsPh 3/Pd 2(dba) 3 at 40 °C followed by column chromatographic purification. The spectral studies indicated that the interaction is stronger in ethynyl bridged BODIPY–chromophore conjugate compared to ethynylphenyl bridged BODIPY–chromophore conjugates. The steady-state fluorescence indicated that in ethynyl bridged BODIPY–anthracene conjugate, the BODIPY unit act as energy acceptor and showed a possibility of energy transfer from donor anthracene unit to acceptor BODIPY unit on selective excitation of anthracene unit. However, in ethynylphenyl bridged BODIPY–porphyrin conjugates, the BODIPY unit act as energy donor and exhibited a possibility of singlet-singlet energy transfer from BODIPY unit to porphyrin unit.

A putrescine–anthracene conjugate: a paradigm for selective drug delivery

Increased polyamine concentrations play an important role in the development of cancer at all stages, from initiation through to maintenance of the transformed phenotype. One way cancer cells accumulate increased concentrations of polyamines is by increased uptake of preformed polyamines via their PTS (polyamine transport system). The PTS is promiscuous and will transport a range of polyamine-based molecules. Therefore it may be that cytotoxic drugs could be attached to polyamine vectors and targeted selectively to cancer cells by utilizing the PTS. The aim of the present study was to investigate the potential of Ant 4, a putrescine–anthracene conjugate, to target cytotoxic agents to human cancer cells as a paradigm for a novel method of selective drug delivery. Ant 4 induced cytotoxicity after only 24 h exposure. Apoptosis was the predominant type of cell death, with mechanistic studies revealing that oxidative stress and DNA damage may have a part to play. For the first time, uptake of Ant 4 via the PTS was demonstrated both directly and indirectly in human cell lines. In addition, Ant 4 significantly reduced putrescine uptake, demonstrating that this conjugate not only used the PTS, but also could successfully compete with its native polyamine for uptake. However, the most interesting finding was the intracellular depletion of the polyamine pools, providing an additional mode of toxicity for Ant 4 and the possibility that this molecule may act as a ‘double-edged sword’: preventing cell growth by delivery of the toxic moiety and by depletion of intracellular polyamine content.

Molecular requirements for targeting the polyamine transport system. Synthesis and biological evaluation of polyamine-anthracene conjugates.

A series of nine N(1)-(9-anthracenylmethyl)tetraamines (e.g., Ant-4,4,4-tetraamine) were synthesized and evaluated for cytotoxicity in L1210, alpha-difluoromethylornithine (DFMO)-treated L1210, Chinese hamster ovary (CHO), and CHO-MG cell lines. Surprisingly, the 3,3,4- and 3,4,3-tetraamine motifs had the same or decreased cytotoxicity in DFMO-treated L1210 cells, whereas the rest of the tetraamine systems were usually more cytotoxic and gave lower IC(50) values in this treated cell line. The most sensitive derivatives to DFMO treatment were the Ant-4,4,3- and Ant-4,4,4-tetraamine analogues, which were 7 and 5 times more cytotoxic in DFMO-treated L1210 cells, respectively. K(i) values for each of the anthracenylmethyl(Ant)-polyamine conjugates were determined in L1210 cells and revealed that these systems are high-affinity ligands for the polyamine transporter (PAT). Mixed results were observed in the CHO and CHO-MG assays. The 4,4,4- and 5,4,4-tetraamine motifs were 3 times more toxic to CHO cells with active polyamine transporters. For example, the Ant-4,4,4-tetraamine conjugate displayed IC(50) values of 11 microM in CHO cells and 33 microM in CHO-MG cells, a PAT-deficient cell line. This suggested that these derivatives used the PAT in part to access cells. However, most of the other tetraamine derivatives had similar potencies in both the CHO and CHO-MG cell lines. In terms of vector design, higher affinity for the PAT (lower K(i) values) did not translate into higher potency for the tetraamine conjugate. In contrast, the related triamine systems, which had micromolar K(i) values in L1210 cells, were more efficacious and selective. In one case, the 4,4-triamine motif imparted 150-fold higher potency in CHO cells than the CHO-MG mutant. A deconvolution microscopy study in A375 melanoma cells revealed a rapid internalization of the Ant-4,4-triamine as fluorescent vesicles, whereas the Ant-4,4,4-tetraamine remained mostly at the cell surface. These findings help define the key characteristics required for selective delivery of polyamine-drug conjugates into cell types with active polyamine transporters.

The Effect of Polyamine Homologation on the Transport and Cytotoxicity Properties of Polyamine−(DNA-Intercalator) Conjugates.

An efficient five-step synthetic method was developed to access a homologous series of spermidine−acridine and spermidine−anthracene conjugates. The derivatives were comprised of a spermidine fragment covalently tethered at its N4 position to either an acridine or anthracene nucleus via an aliphatic chain (e.g., spermidine−[aliphatic tether]−acridine). The distance separating the spermidine and aromatic nucleus was altered by using different tethers comprised of four or five methylene units, respectively. These ligands (2−5) were shown to inhibit human DNA topoisomerase-II (TOPO-II) activity at 10 μM. Enzymatic activity was assessed as the ability to unknot (decatenate) and cleave kinetoplast DNA (kDNA). Polyamine conjugation did not disrupt the ability of the acridine−spermidine conjugates 2 and 3 to inhibit TOPO-II activity as compared with the 9-aminoacridine and 9-(N-butyl)aminoacridine controls (at 10 μM). In general, the acridine derivatives (2 and 3) showed higher TOPO-II inhibitory activity than t...

Fluorescent conjugates of natural and biosynthetic polynucleotides

The fluorescence properties of acriflavine and methylbenz( a)anthracene conjugates of DNA and several biosynthetic polyribonucleotides have been examined and compared. Both types of label respond in a qualitatively similar way to helix → coil transitions involving the polynucleotides. While the terminal-labeled acriflavine conjugates showed only a single fluorescence decay time, the methylbenz( a)anthracene conjugates gave decay curves which could best be fitted on the assumption of two fluorescent species, with different decay times. When labeled poly(rA) was incorporated into the rA : rU bihelical complex the extent to which rotational mobility, as measured by polarization, was lost at the early stages of complex formation differed for the two labels.