Polycyclic Aromatic Moiety Research Articles

Quadruplex-duplex junction in LTR-III: A molecular insight into the complexes with BMH-21, namitecan and doxorubicin.

Quadruplex-Duplex (Q-D) junctions are unique structural motifs garnering increasing interest as drug targets, due to their frequent occurrence in genomic sequences. The viral HIV LTR-III sequence was chosen as a Q-D junction model to study the affinity of the selected compounds BMH-21, namitecan (ST-1968), and doxorubicin (DOXO), all containing a planar polycyclic aromatic moiety, linked to either one short aminoalkyl or an aminoglycosyl group. A multidisciplinary approach that combines NMR spectroscopy, molecular modelling, circular dichroism (CD) and fluorescence spectroscopy was employed. The studied ligands induced moderate but clear stabilization to the Q-D junction by interacting with the interfacial tetrad. DOXO was found to be the best Q-D junction binder. Interestingly, the removal of the aminoglycosyl group significantly changed the pattern of the interactions, indicating that highly polar substituents have a stronger affinity with the exposed regions of the Q-D junction, particularly at the level of the interfacial tetrad.

Anthracene-based dual channel donor-acceptor triazine-containing covalent organic frameworks for superior photoelectrochemical sensing

Covalent organic frameworks (COFs) exhibit excellent photoelectrically active structures and serve as channels for photon capture and charge carrier transport. However, their relatively high charge-carrier recombination rates and lack of specific recognition sites limit their application in photoelectrochemical sensing. This paper reports a functionalized donor–acceptor (D-A) COF comprising electron-rich polycyclic aromatic moieties and electron-deficient triazines (Tz) incorporating boronic acid through ligand exchange. The number of aromatic rings in the polycyclic aromatic moiety is crucial for establishing an efficient D-A system within COF. In the absence of an external electron donor, the anthracene-based COF exhibited a five-fold enhancement in photocurrent compared to the naphthalene-based COF. The resulting anthracene-based D-A COF exhibited enhanced orbital overlap and electron push–pull interactions, facilitating more effective charge separation. Furthermore, introducing boronic acid enabled the selective enrichment of low-concentration external electron donors, such as dopamine, in the inner Helmholtz plane. This ingenious approach establishes a unique dual-channel D-A system that allows direct measurement of dopamine in serum. Under optimized conditions, the test platform achieves good correspondence for dopamine at 1 to 100 nM and 0.5 to 100 μM with a detecting limit of 0.36 nM (3σ/S, n = 11). This strategy introduces a novel dimension to photoelectrochemical sensing, focusing on the effect of spatial separation between the external electron donor and the photoelectrode interface that intricately shapes the behavior and enhances the performance of the photoelectric system.

Design of an anticancer organoruthenium complex as the guest and polydiacetylene-coated fluorogenic nanocarrier as the host: engineering nanocarrier using ene-yne conjugation for sustained guest release, enhanced anticancer activity and reduced in vivo toxicity.

Despite the enormous efforts made over the past two decades to develop metallodrugs and nanocarriers for metallodrug delivery, there are still few precise strategies that aim to optimize the design of both metallodrugs and metallodrug carriers jointly in a concerted effort. In this work, three half-sandwich ruthenium(II) complexes with pyridylimidazo[1,5-a]pyridine ligand functionalized with polycyclic aromatic moiety (Ru(nap), Ru(ant), Ru(pyr)) are evaluated as possible anticancer candidates and polydiacetylene (PDA)-coated amino-functionalized mesoporous silica nanoparticles (AMSNs) are designed as a functional nanocarrier for drug delivery. Ru(pyr) exhibits higher cytotoxicity in HT-29 colorectal cancer cells compared to other complexes and cis-platin, but it does not exhibit better cellular uptake. Ru(pyr) is found to be preferentially accumulated in plasma, mitochondria, and ER-Golgi membrane. The complex induces cell cycle arrest in the G0/G1 phase, while higher concentrations cause programmed cell death via apoptosis. Ru(pyr) influences cancer cell adhesion property and acts as an antioxidant in HT-29 cells. In order to modulate the anticancer potency of Ru(pyr), AMSNs are used to encapsulate the complex, and then diacetylene self-assembly is allowed to deposit on the surface of the nanoparticles. Subsequently, the nanoparticles undergo topopolymerization, which results in π-conjugated PDA-Ru(pyr)@AMSNs. Owing to the ene-yne polymeric skeleton in the backbone, the non-fluorescent AMSNs turn into red-emissive particles, which are exploited for cell imaging applications. The release profile analysis reveals that such a π-conjugated polymer prevents the premature release of the complex from porous silica nanoparticles with the accelerated release of the complex in an acidic medium compared to physiological conditions. The PDA gatekeepers have also been proven to enhance the cellular internalization of Ru(pyr) with slow continuous release from the nanoformulation. Zebrafish embryo toxicity analysis suggests that the PDA-coated nanocarriers could be suitable candidates for in vivo investigations.

Machine learning-assisted exploration of a versatile polymer platform with charge transfer-dependent full-color emission

<h2>Summary</h2> The development of color-tunable fluorescent materials with simple chemical compositions that are easy to synthesize is highly desirable but practically challenging. Here, we report a versatile yet simple platform based on through-space charge transfer (TSCT) polymers that has full-color-tunable emission and was developed with the aid of predictive machine learning models. Using a single-acceptor fluorophore as the initiator for atom transfer radical polymerization, a series of electron donor groups containing simple polycyclic aromatic moieties (e.g., pyrene) are introduced either by one-step copolymerization or by end-group functionalization of a pre-synthesized polymer. By manipulating donor-acceptor interactions via controlled polymer synthesis, continuous blue-to-red emission color tuning was easily achieved in solid polymers. Theoretical investigations confirm the structurally dependent TSCT-induced emission redshifts. We also exemplify how these TSCT polymers can be used as a general design platform for solid-state stimuli-responsive materials with high-contrast photochromic emission by applying them to proof-of-concept information encryption.

Anthryl Benzothiazolium Molecular Rotor-Based Turn-On DNA Probe: Detailed Mechanistic Studies.

An efficient turn-on fluorescence probe for biomolecules not only helps in its sensitive detection but is also useful to understand the different interactions that are operating between biomolecules and probes. Polycyclic aromatic molecules are known to be strong interacting ligand for DNA and extensively studied as a model cancer drug. However, these molecules show large decrease in their emission intensity, i.e., a turn-off probe for DNA. In the present work, we have synthesized a benzothiazole-based anthracene derivative and studied its interaction with a natural DNA with the aim of having a turn-on DNA probe with a polycyclic aromatic moiety. Our detailed spectroscopic studies show that the new probe strongly interacts with DNA molecules and results in a significant increase in its emission yield. Time-resolved studies show a large increase in probe's excited-state lifetime in DNA solution. Detailed experiments have been performed to understand its mode of interaction with DNA molecules. The mode of interaction has also been supported by the blind molecular docking studies. Further, the viscosity-dependent photophysical properties and detailed quantum chemical calculations confirm that the new probe belongs to molecular rotor class of molecules. Association with DNA molecules results in a significant retardation in the nonradiative deactivation process due to the torsional motion in the excited state of the probe and leads to a significant increase in its emission yield. Thus, due its molecular rotor nature, despite with a turn-off fluorophore unit, anthracene, the new probe, acts as a sensitive turn-on fluorescence probe for DNA molecules.

Highly Cytotoxic Ruthenium(II)-Arene Complexes from Bulky 1-Pyrenylphosphane Ligands.

In the present study, the potential anti-neoplastic properties of a series of ruthenium half-sandwich complexes of formula [Ru(η6-arene)Cl2(PR1R2(1-pyrenyl))] (η6-arene = p-cymene and R1 = R2 = methyl for 1; η6-arene = methylbenzoate and R1 = R2 = methyl for 2; η6-arene = p-cymene and R1 = R2 = phenyl for 3; η6-arene = methylbenzoate and R1 = R2 = phenyl for 4; η6-arene = p-cymene, R1 = methyl and R2 = phenyl for 5; η6-arene = methylbenzoate, R1 = methyl and R2 = phenyl for 6) have been investigated. The six structurally related organoruthenium(II) compounds have been prepared in good yields and fully characterized; the X-ray structures of three of them, i.e., 1, 2, and 4, were determined. Although the piano-stool compounds contain a large polycyclic aromatic moiety, viz. a 1-pyrenyl group, they do not appear to interact with DNA. However, all the piano-stool complexes show significant cytotoxic properties against five human cell lines, namely, lung adenocarcinoma (A549), melanoma (A375), colorectal adenocarcinoma (SW620), breast adenocarcinoma (MCF7), and nontumorigenic epithelial breast (MCF10A), with IC50 values in the micromolar range for most of them. In addition, the most active compound, i.e., 2, induces a remarkable decrease of cell viability, that is in the nanomolar range, against two human neuroblastoma cell lines, namely, SK-N-BE(2) and CHLA-90. Complexes 1-6 are all capable of inducing apoptosis, but with various degrees of magnitude. Whereas 1, 3, 5, and 6 have no effect on the cell cycle of A375 cells, 2 and 4 can arrest it at the G2/M phase; furthermore, 2 (which is the most efficient compound of the series) also stops the cycle at the S phase, behaving as the well-known anticancer agent cisplatin. Finally, 2 is able to inhibit/reduce the cell migration of neuroblastoma SK-N-BE(2) cells.

Synthesis, Structural Characterization, and Photophysical, Spectroelectrochemical, and Anion-Sensing Studies of Heteroleptic Ruthenium(II) Complexes Derived from 4′-Polyaromatic-Substituted Terpyridine Derivatives and 2,6-Bis(benzimidazol-2-yl)pyridine

Heteroleptic bis-tridentate ruthenium(II) complexes of composition [(H2pbbzim)Ru(tpy-Ar)](ClO4)2, where H2pbbzim = 2,6-bis(benzimidazol-2-yl)pyridine and tpy-Ar = 4'-substituted terpyridine ligands with Ar = phenyl (2), 2-naphthyl (3), 9-anthryl (4), and 1-pyrenyl (5) groups, have been synthesized and characterized by using standard analytical and spectroscopic techniques. The X-ray crystal structures of the complexes [(H2pbbzim)Ru(tpy-Naph)](ClO4)2 (3), [(pbbzim)Ru(tpy-Naph)]·(CH3)2CO·H2O (3a), and [(H2pbbzim)Ru(tpy-Py)](ClO4)2 (5) have been determined. The absorption, steady-state, and time-resolved luminescence spectral properties of the complexes were thoroughly investigated in dichloromethane. The compounds display strong luminescence at room temperature with lifetimes (τ2) in the range of 5.5-62 ns, depending upon the nature of the polycyclic aromatic moiety as well as the solvents. The complexes are found to undergo one reversible oxidation in the positive potential window (0 to +1.5 V) and four successive quasi-reversible reductions in the negative potential window (0 to -2.4 V). The anion-sensing properties of the receptors were thoroughly investigated in acetonitrile/dichloromethane (1/9 v/v) solutions (2 × 10(-5) M) using absorption, steady-state, and time-resolved emission spectroscopic studies. (1)H NMR titration experiments, on the other hand, were carried out in either CD3CN or DMSO-d6. The anion-sensing studies revealed that the receptors act as sensors for F(-), CN(-), AcO(-), and SO4(2-) and to some extent for HSO4(-) and H2PO4(-). It is evident that, in the presence of excess anions, deprotonation of the imidazole N-H fragments of the receptors occurs, which is signaled by the change of color from yellow-orange to violet visible with the naked eye. From the absorption and emission titration studies the binding/equilibrium constants of the receptors with the anions have also been determined. Anion-induced lifetime quenching and/or enhancement make the receptors suitable lifetime-based sensors for selective anions. Cyclic voltammetric (CV) measurements of the compounds carried out in acetonitrile have provided evidence in favor of anion-dependent electrochemical responses with F(-) and AcO(-) ions. Spectroelectrochemical studies have also been carried out for both the protonated and deprotonated forms of the complexes in the range of 300-1200 nm. With successive oxidation of the Ru(II) center, replacement of MLCT bands by LMCT bands occurs gradually with observation of sharp isosbestic points in all cases.

Dispersion of carbon nanotubes by carbazole-tailed amphiphilic imidazolium ionic liquids in aqueous solutions

Surfactants with a polycyclic aromatic moiety and a long hydrocarbon chain, carbazole-tailed amphiphilic imidazolium ionic liquids 1-[ n-( N-carbazole)alkyl]-3-methylimidazolium bromide [CzC n MIm]Br ( n = 10 and 12), were designed to disperse carbon nanotubes (CNTs) in aqueous solutions. UV–vis–NIR spectra were performed to determine the dispersion of CNTs and the optimal concentration ( C opt) of [CzC n MIm]Br. Compared with [C n MIm]Br, [CzC n MIm]Br was more effective with the smaller C opt and more individual CNTs, reflecting the effect of the carbazole moiety. The adsorption of [CzC n MIm]Br molecules on CNTs was investigated by zeta-potential, surface tension, fluorescence, and 1H NMR. Having zeta-potentials higher than 15 mV contributed to the long-term stability of aqueous CNT dispersions. The significant fluorescence quenching and the upfield shift of carbazole protons support the π– π stacking interaction between carbazole moieties and the π-networks of CNTs. Meanwhile, the upfield shift of imidazolium protons indicates the cation– π interaction between the imidazolium ions and the π-networks of CNTs.

Charge balance materials for homojunction and heterojunction OLED applications

In a homojunction device, a single organic layer assumes the multiple roles of hole, electron transportation, and emitter. Its ease in processing is highly desirable from the manufacturing point of view. In this paper, we shall describe the synthesis of a range of bipolar small molecules and conductive vinyl polymers for application in homojunction and heterojunction organic light emitting diodes (OLEDs). The bipolar materials, in general, consist of three basic building blocks: an arylamine, a 1,3,4-oxadiazole, and a polycyclic aromatic moiety. The achievement of charge balance can be validated either by direct measurement of electron/hole mobility or indirectly via optimization of device properties. A series of conductive vinyl copolymers containing hole transporting N-(4-methoxyphenyl)-N-(4-vinylphenyl)naphthalen-1-amine (4MeONPA) and electron transporting 2-phenyl-5-(4-vinylphenyl)-1,3,4-oxadiazole (OXA) at different compositions was applied for heterojunction and homojunction OLEDs. For heterojunction devices employed the copolymers as the hole transporting layer and Alq3 as the electron transporting and emitting layer, a maximum luminance and current efficiency of over 23000 cd/m2 and 4.2 cd/A (PL of Alq3), respectively, were achieved at the charge balance composition. Homojunction devices for the copolymers were demonstrated by the addition of rubrene as a dopant. The single layer devices at the optimal copolymer composition has ca 1500 cd/m2 and 0.74 cd/A.

Complementary Multianalytical Approach To Study the Distinctive Structural Features of the Main Humic Fractions in Solution: Gray Humic Acid, Brown Humic Acid, and Fulvic Acid

Previous studies have indicated that the main fractions of humic substances (HS), gray humic acid (GHA), brown humic acid (BHA), and fulvic acid (FA), present different molecular patterns in water solution that are probably associated with specific structural features. However, the techniques used in these previous studies did not permit clarification of the principal qualitative characteristics of these structures. To study more in depth this subject several GHA, BHA, and FA have been analyzed through the complementary use of UV-visible and FTIR spectroscopy, (13)C NMR, thermogravimetry, and pyrolysis GC-MS. The results indicate that the studied humic fractions have different and distinctive structural features. Thus, large and nonpolar structural units (paraffins, olefins, terpenes) and aliphatic structures seem to accumulate in the gray fraction, whereas the smallest and more polar (furfural, phenols) and simpler structural units (sugar- and amino acid-related structures) are present in the fulvic one. BHA has a higher content in polycyclic aromatic moieties, S-containing compounds and aromatic structures, thus suggesting the presence of more condensed aromatic rings. Likewise, differences in both the presence of polar groups and the apparent molecular size explain the pattern of solubility as a function of pH and ionic strength (I) that defines each HS fraction. These results also indicate that the structural differences among the HS fractions are not only quantitative (the presence of the same type of structures differing in size and the concentration of functional groups) but also qualitative, because each fraction presented different and distinctive structural domains. These structural domains explain the molecular patterns associated with each HS fraction. Thus, the presence of smaller and more O-functionalized structural units including aromatic domains in FA explain their tendency to form molecular aggregates (hydrogen bridges, metal bridges, and hydrophobic interactions) in solution. This fact could also explain the presence of molecular aggregates in BHA, although to a lesser extent than in FA. Finally, the dominant aliphatic and less functionalized character of GHA may justify its lower tendency to form aggregates in solution at neutral and alkaline pH. Likewise, the results also indicate that the different structural domains associated with these fractions may be the consequence of diverse biosynthetic pathways involving different precursors.

Rational Attempts to Optimize Non-Natural Nucleotides for Selective Incorporation Opposite an Abasic Site

Translesion DNA synthesis represents the ability of a DNA polymerase to misinsert a nucleotide opposite a DNA lesion. Previous kinetic studies of the bacteriophage T4 DNA polymerase using a series of non-natural nucleotides suggest that pi-electron density of the incoming nucleotide substantially contributes to the efficiency of incorporation opposite an abasic site, a nontemplating DNA lesion. However, it is surprising that these nonhydrogen-bonding analogues can also be incorporated opposite natural templating DNA with variable degrees of efficiency. In this article, we describe attempts to achieve selectivity for incorporation opposite the abasic site through optimization of pi-electron density and shape of the nucleobase. Toward this goal, we report the synthesis and enzymatic characterization of two novel nucleotide analogues, 5-napthyl-indolyl-2'-deoxyriboside triphosphate (5-NapITP) and 5-anthracene-indolyl-2'-deoxyriboside triphosphate (5-AnITP). The overall catalytic efficiency for their incorporation opposite an abasic site is similar to that of other non-natural nucleotides such as 5-NITP and 5-PhITP that contain significant pi-electron density. As expected, the incorporation of either 5-NapITP or 5-AnITP opposite templating DNA is reduced and presumably reflects steric constraints imposed by the large size of the polycyclic aromatic moieties. Furthermore, 5-NapITP is a chain terminator of translesion DNA synthesis because the DNA polymerase is unable to extend beyond the incorporated non-natural nucleotide. In addition, idle turnover measurements confirm that 5-NapIMP is stably incorporated opposite damaged DNA, and this enhancement reflects the overall favorable incorporation kinetic parameters coupled with a reduction in excision by the exonuclease-proofreading activity of the enzyme. On the basis of these data, we provide a comprehensive assessment of the potential role of pi-electron surface area for nucleotide incorporation opposite templating and nontemplating DNA catalyzed by the bacteriophage T4 DNA polymerase.

Interaction of substituted cobalt(III) cage complexes with DNA †

Polycyclic aromatic moieties covalently bound to the inert cationic cobalt(III)–sar cage complex (sar = sarcophagine = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) intercalate with negatively supercoiled plasmid DNA, as shown by both spectrophotometric and gel electrophoresis studies. Although anthracene itself is not a good intercalating agent, the association constant of the complex between anthracene tied to the cobalt(III)–sar cage and DNA is ≈2 × 106 dm3 mol−1 and the average binding-site size on supercoiled plasmid DNA is ≈2.4 base pairs. The hydrophilic complex cation (a) solubilizes the anthracene moiety in water and (b) enhances DNA binding by its electrostatic interaction with the anionic phosphodiester backbone of DNA. While irradiation of the intercalated complexes at 254 nm led to single-strand cleavage of DNA, irradiation at higher wavelength, 302 and 365 nm, was much less effective. Neither molecular oxygen nor excited singlet or triplet states of anthracene appear to be involved in the cleavage process, and it is likely that the N-radical cation arising from ligand to metal charge or electron transfer in the phosphodiester–complex ion pair gives rise to oxidation of the deoxyribose moieties. Fission of the resulting deoxyribose diphosphate radical cation follows, leading to DNA single-strand cleavage. It also appears that the most easily reduced complex moieties are the most effective cleavage agents. Excited singlet and triplet states of anthracene arising from irradiation at 365 nm are efficiently quenched by DNA and the allowedness of the short-axis in-plane aromatic transitions is also sharply diminished. This in itself is unusual.

Differential Hydration Thermodynamics of Stereoisomeric DNA−Benzo[a]pyrene Adducts Derived from Diol Epoxide Enantiomers with Different Tumorigenic Potentials

A combination of UV spectroscopy, calorimetry, and density techniques were used to characterize the thermodynamics of complexes with covalently bound hydrophobic pyrenyl residues in the minor groove of DNA undecamer duplexes. The control duplex d(CCATCG*CTACC)/d(GGTAGCGATGG) and two adduct duplexes in which the chiral (+)-anti-BPDE and (−)-anti-BPDE (the 7R,8S,9S,10R- and 7S,8R,9R,10S-enantiomers of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) had been reacted covalently with the exocyclic amino group of the guanine residue G* were studied (designated as the (+)- and (−)-BPDE duplexes, respectively). Both of the BPDE-modified DNA duplexes exhibit lower helix-coil transition temperatures than the control duplex. The complete thermodynamic profiles (ΔV, ΔH, ΔG, ΔS, and ΔnNa+) for the formation of each duplex were determined at 20 °C. Duplex formation is primarily enthalpy driven, and is accompanied by an uptake of both counterions and water molecules (negative ΔV). Relative to the unmodified duplex, the differential thermodynamic profiles of each covalent adduct duplex reveal an enthalpy−entropy compensation; the ΔΔV value is only marginally smaller for the (−)-BPDE−DNA than for the unmodified duplex, but the uptake of water is nearly 50% greater for the (+)-BPDE duplex. Correlation of the thermodynamic data with the known NMR solution conformations of the BPDE−DNA complexes (de los Santos et al. Biochemistry 1992, 31, 5245) suggests that these differential thermodynamic parameters, together with the similar values for the uptake of counterions, correspond to a differential hydration of the BPDE residues that are exposed to solvent while in the minor groove of B-DNA. The formation of the (+)-BPDE duplex results in a greater immobilization of structural water than in the case of the (−)-BPDE duplex; these results suggest that the bent conformation at the lesion site apparently gives rise to an enhanced exposure of the hydrophobic polycyclic aromatic moiety of the covalently bound BPDE residue to the aqueous solvent.