Naphthalene Diimide Ligands Research Articles

Nickel(ii) metal–organic frameworks with N,N′-di(4-pyridyl)-naphthalenediimide ligands: influence of secondary building unit geometry on dimensionality and framework dimensions

The influence of intermolecular interactions and metal coordination geometry on MOF framework dimensions are discussed.

A robust metallomacrocyclic motif for the formation interpenetrated coordination polymers

The reproducibility of an M2L2 metallomacrocyclic synthon containing L-alanine substituted naphthalene diimide ligands (AlaNDI), and its ability to form both catenane and rotaxane motifs, has been demonstrated in a series of nine homochiral coordination polymers. The planes of the NDIs that comprise the metallomacrocycle are ∼7 A apart, an ideal distance for an aromatic group to reside within the ring with multiple parallel π-interactions. The tendency for these systems to be dominated by π-interactions appears to be a driving force for interpenetration of these coordination polymers by either the formation of catenanes between two {M2(AlaNDI)2} metallomacrocycles or the formation of rotaxanes by dipyridyl coligands passing through metallomacrocycles (4,4′-bipyridine, dipyridylethene and dipyridylnaphthalenediimide). Due to both of these interpenetration motifs being facilitated by parallel π-interactions, the interpenetration of the individual networks does not typically lead to increased dimensionality in the structures, with the exception of one material in which a 1D chain interpenetrates in a 1D → 2D manner. Two of the reported coordination polymers, both containing dipyridylnaphthalenediimide (4PyNDI), are not interpenetrated with π-interactions present between the 4PyNDI ligands themselves rather than engaging with the macrocycles. Overall the reproducibility of the metallomacrocycle, and the relatively common occurrence of catenane and rotaxane motifs, suggests that this is a promising synthon for further crystal engineering applications.

Ferrocenyl naphthalene diimides as tetraplex DNA binders

Seven ferrocenyl naphthalene diimide (FND) ligands were synthesized. Each had a higher affinity for tetraplex DNA than for either single- or double-stranded DNA. The FND binding affinities were >105M−1 in 0.10M AcOH-AcONa or AcOH-AcOK (pH5.5) containing 0.10M NaCl or KCl. The FNDs with the highest binding affinities for tetraplex DNA showed 23- or 8-times higher preference for tetraplex DNA than for single- or double-stranded DNA, respectively. The current signals generated from the seven FNDs bound to the tetraplex DNA immobilized on the electrode were found to correlate with the binding affinities of these ligands for the tetraplex DNA. Furthermore, using the telomerase repeat amplification protocol assay, the FND ligands could be categorized into three groups: (a) inhibiting both telomerase and Taq polymerase, (b) inhibiting telomerase alone, and (c) inhibiting neither telomerase nor Taq polymerase.

Transparent-to-Dark Electrochromic Behavior in Naphthalene-Diimide-Based Mesoporous MOF-74 Analogs

Summary The deliberate insertion of redox-active naphthalene diimide ligands into the versatile family of metal-organic frameworks known as MOF-74 (CPO-27) gives rise to a mesoporous electrochromic MOF that can be switched from transparent to dark, a desirable feature in electrochromic devices such as smart windows. Specifically, we report two new materials that have the MOF-74 topology and display redox activity stemming from a naphthalene diimide salicylic acid (NDISA) ligand. We show that these materials can be deposited as thin films on fluorine-doped tin oxide glass. The surprisingly different morphologies of MOF films obtained from Mg 2+ and Ni 2+ ions is likely controlled by the nucleation kinetics of Mg 2 (NDISA) and Ni 2 (NDISA), respectively. Both materials exhibit well-behaved quasi-reversible redox events associated with the [NDI]/[NDI] ·– and [NDI] ·– /[NDI] 2– redox couples, which are also responsible for the electrochromic switching.

Molecular recognition of naphthalene diimide ligands by telomeric quadruplex-DNA: the importance of the protonation state and mediated hydrogen bonds.

In depth Monte Carlo conformational scans in combination with molecular dynamics (MD) simulations and electronic structure calculations were applied in order to study the molecular recognition process between tetrasubstituted naphthalene diimide (ND) guests and G-quadruplex (G4) DNA receptors. ND guests are a promising class of telomere stabilizers due to which they are used in novel anticancer therapeutics. Though several ND guests have been studied experimentally in the past, the protonation state under physiological conditions is still unclear. Based on chemical intuition, in the case of N-methyl-piperazine substitution, different protonation states are possible and might play a crucial role in the molecular recognition process by G4-DNA. Depending on the proton concentration, different nitrogen atoms of the N-methyl-piperazine might (or might not) be protonated. This fact was considered in our simulation in terms of a case by case analysis, since the process of molecular recognition is determined by possible donor or acceptor positions. The results of our simulations show that the electrostatic interactions between the ND ligands and the G4 receptor are maximized in the case of the protonation of the terminal nitrogen atoms, forming compact ND G4 complexes inside the grooves. The influence of different protonation states in terms of the ability to form hydrogen bonds with the sugar-phosphate backbone, as well as the importance of mediated vs. direct hydrogen bonding, was analyzed in detail by MD and relaxed force constant (compliance constant) simulations.

Synthesis, fluorescence, and sorption properties of cobalt coordination polymers of the N,N′-bis(4-pyridylmethyl)naphthalene diimide ligand

Three cobalt coordination polymers, namely {[Co(4-pmntd)2(CF3SO3)(H2O)]·(CF3SO3)·(C2H5OH)·0.5(HCCl3)·H2O} n (1), {[Co(4-pmntd)(H2O)4]·(NO3)2·H2O} n (2), and {[Co(4-pmntd)(pta)(CH3OH)2]·2(CHCl3)} n (3) (4-pmntd = N,N′-bis(4-pyridylmethyl)-naphthalene diimide; pta = terephthalate), have been synthesized by reactions of 4-pmntd with Co(CF3SO3)2·4H2O, Co(NO3)2·6H2O, and Co(pta), respectively. The complexes have been characterized by elemental analyses, powder X-ray diffraction, thermogravimetric analyses, IR spectroscopy, and single-crystal X-ray diffraction. In complex 1, the ligand adopts U-mode, resulting in a dumbbell-like 2D (4, 4)-sql net structure in a non-interpenetrating edge-to-edge arrangement. The Z-mode ligand arrangement leads to 1D zigzag chains for complex 2, and a 2D twofold interpenetrating bat-like (4, 4)-sql net for complex 3. A solution of complex 2 in DMF showed a change in color and remarkably enhanced fluorescence upon the addition of two equivalents of acetate, whereas other anions did not induce a color change. Hence, complex 2 can act as a highly promising acetate-detecting reagent. Their thermal and the gas adsorption properties of complexes 1 and 3 were investigated. Three 1D and 2D cobalt coordination polymers have been synthesized; their structural diversity in these complexes is attributed to different coordination abilities, geometries of counter-anions, and the different conformations adopted by the ligand. A solution of complex 2 showed a change in color and remarkably enhanced fluorescence upon the addition of two equivalents of acetate, whereas other anions did not induce a color change. Hence complex 2 can act as a highly promising acetate-detecting reagent. Their thermal properties and the gas adsorption property of complexes 1, 3 were investigated.

Thermodynamics of binding of di- and tetrasubstituted naphthalene diimide ligands to DNA G-quadruplex.

Naphthalene diimide ligands have the potential to stabilize human telomeric G-quadruplex DNA via noncovalent interactions. Stabilization of G-quadruplex high order structures has become an important strategy to develop novel anticancer therapeutics. In this study four naphthalene diimide based ligands were analyzed in order to elucidate the principal factors determining contributions to G-quadruplex-ligand binding. Three possible modes of binding and their respective Gibbs free energies for two naphthalene diimide based di-N-alkylpyridinium substituted ligands have been determined using a molecular docking technique and compared to experimental results. The structures obtained from the molecular docking calculations, were analyzed using the ab initio based fragment molecular orbital (FMO) method in order to determine the major enthalpic contributions to the binding and types of interactions between the ligand and specific residues of the G-quadruplex. A computational methodology for the efficient and inexpensive ligand optimization as compared to fully ab initio methods based on the estimation of binding affinities of the naphthalene diimide derived ligands to G-quadruplex is proposed.

Broadband visible-light-harvesting trans-bis(alkylphosphine) platinum(II)-alkynyl complexes with singlet energy transfer between BODIPY and naphthalene diimide ligands.

A heteroleptic bis(tributylphosphine) platinum(II)-alkynyl complex (Pt-1) showing broadband visible-light absorption was prepared. Two different visible-light-absorbing ligands, that is, ethynylated boron-dipyrromethene (BODIPY) and a functionalized naphthalene diimide (NDI) were used in the molecule. Two reference complexes, Pt-2 and Pt-3, which contain only the NDI or BODIPY ligand, respectively, were also prepared. The coordinated BODIPY ligand shows absorption at 503 nm and fluorescence at 516 nm, whereas the coordinated NDI ligand absorbs at 594 nm; the spectral overlap between the two ligands ensures intramolecular resonance energy transfer in Pt-1, with BODIPY as the singlet energy donor and NDI as the energy acceptor. The complex shows strong absorption in the region 450 nm-640 nm, with molar absorption coefficient up to 88 000 M(-1) cm(-1) . Long-lived triplet excited states lifetimes were observed for Pt-1-Pt-3 (36.9 μs, 28.3 μs, and 818.6 μs, respectively). Singlet and triplet energy transfer processes were studied by the fluorescence/phosphorescence excitation spectra, steady-state and time-resolved UV/Vis absorption and luminescence spectra, as well as nanosecond time-resolved transient difference absorption spectra. A triplet-state equilibrium was observed for Pt-1. The complexes were used as triplet photosensitizers for triplet-triplet annihilation upconversion, with upconversion quantum yields up to 18.4 % being observed for Pt-1.

Enhanced phosphorescence emission by incorporating aromatic halides into an entangled coordination framework based on naphthalenediimide.

Phosphorescence emission at room temperature is turned on in an entangled porous coordination polymer (PCP) with naphthalenediimide (NDI) as chromophore, by incorporating halogenated guests into the pores. The phosphorescent efficiency is drastically increased by the incorporation of aromatic halide guests in comparison with the incorporation of nonaromatic derivatives. Aromatic halide guests trigger a structural transformation, which allows a strong interaction with the NDI ligand in the framework through charge-transfer complexation, and provides an extra population process of the triplet state. The long-lived photoinduced triplet states, with an emission wavelength in the red region of the visible spectrum, demonstrated by this PCP, may open the door for potential uses, for example, as singlet-oxygen generators or for bio-imaging applications.

New insights from molecular dynamic simulation studies of the multiple binding modes of a ligand with G-quadruplex DNA

G-quadruplexes are higher-order DNA and RNA structures formed from guanine-rich sequences. These structures have recently emerged as a new class of potential molecular targets for anticancer drugs. An understanding of the three-dimensional interactions between small molecular ligands and their G-quadruplex targets in solution is crucial for rational drug design and the effective optimization of G-quadruplex ligands. Thus far, rational ligand design has been focused mainly on the G-quartet platform. It should be noted that small molecules can also bind to loop nucleotides, as observed in crystallography studies. Hence, it would be interesting to elucidate the mechanism underlying how ligands in distinct binding modes influence the flexibility of G-quadruplex. In the present study, based on a crystal structure analysis, the models of a tetra-substituted naphthalene diimide ligand bound to a telomeric G-quadruplex with different modes were built and simulated with a molecular dynamics simulation method. Based on a series of computational analyses, the structures, dynamics, and interactions of ligand-quadruplex complexes were studied. Our results suggest that the binding of the ligand to the loop is viable in aqueous solutions but dependent on the particular arrangement of the loop. The binding of the ligand to the loop enhances the flexibility of the G-quadruplex, while the binding of the ligand simultaneously to both the quartet and the loop diminishes its flexibility. These results add to our understanding of the effect of a ligand with different binding modes on G-quadruplex flexibility. Such an understanding will aid in the rational design of more selective and effective G-quadruplex binding ligands.

Mechanism of the antiproliferative activity of some naphthalene diimide G-quadruplex ligands.

G-quadruplexes are higher-order nucleic acid structures that can form in G-rich telomeres and promoter regions of oncogenes. Telomeric quadruplex stabilization by small molecules can lead to telomere uncapping, followed by DNA damage response and senescence, as well as chromosomal fusions leading to deregulation of mitosis, followed by apoptosis and downregulation of oncogene expression. We report here on investigations into the mechanism of action of tetra-substituted naphthalene diimide ligands on the basis of cell biologic data together with a National Cancer Institute COMPARE study. We conclude that four principal mechanisms of action are implicated for these compounds: 1) telomere uncapping with subsequent DNA damage response and senescence; 2) inhibition of transcription/translation of oncogenes; 3) genomic instability through telomeric DNA end fusions, resulting in mitotic catastrophe and apoptosis; and 4) induction of chromosomal instability by telomere aggregate formation.

Improving the affinity of naphthalene diimide ligand to telomeric DNA by incorporating Zn2+ ions into its dipicolylamine groups

N,N′-bis[3-[3-(2,2′-dipicolyl)methylaminopropyl]-methylaminopropyl]naphthalene-1,4,5,8-tetracarboxylic acid diimide, 1, and its complex with zinc ions, 2, were investigated against telomeric sequences, [TAGGG(TTAGGG)3] and [AGGG(TTAGGG)3], which reveal different G-quadruplex structures depending on the conditions. Spectrophotometric, SPR, and CD techniques revealed that both ligands showed large binding constants to hybrid-type G-quadruplexes formed in the presence of K+ ions. Moreover, 2 revealed higher affinity to investigated oligonucleotides suggesting that complex of naphthalene diimide derivative with Zn2+, comparing to 1, provided additional electrostatic or coordination interactions between positively charged zinc ions and condensed negative charged phosphate anions from G4 DNA.

Structural Basis for Telomeric G-Quadruplex Targeting by Naphthalene Diimide Ligands

The folding of the single-stranded 3' end of the human telomere into G-quadruplex arrangements inhibits the overhang from hybridizing with the RNA template of telomerase and halts telomere maintenance in cancer cells. The ability to thermally stabilize human telomeric DNA as a four-stranded G-quadruplex structure by developing selective small molecule compounds is a therapeutic path to regulating telomerase activity and thereby selectively inhibit cancer cell growth. The development of compounds with the necessary selectivity and affinity to target parallel-stranded G-quadruplex structures has proved particularly challenging to date, relying heavily upon limited structural data. We report here on a structure-based approach to the design of quadruplex-binding ligands to enhance affinity and selectivity for human telomeric DNA. Crystal structures have been determined of complexes between a 22-mer intramolecular human telomeric quadruplex and two potent tetra-substituted naphthalene diimide compounds, functionalized with positively charged N-methyl-piperazine side-chains. These compounds promote parallel-stranded quadruplex topology, binding exclusively to the 3' surface of each quadruplex. There are significant differences between the complexes in terms of ligand mobility and in the interactions with quadruplex grooves. One of the two ligands is markedly less mobile in the crystal complex and is more quadruplex-stabilizing, forming multiple electrostatic/hydrogen bond contacts with quadruplex phosphate groups. The data presented here provides a structural rationale for the biophysical (effects on quadruplex thermal stabilization) and biological data (inhibition of proliferation in cancer cell lines and evidence of in vivo antitumor activity) on compounds in this series and, thus, for the concept of telomere targeting with DNA quadruplex-binding small molecules.

Tetrasubstituted naphthalene diimide ligands with selectivity for telomeric G-quadruplexes and cancer cells

A series of tetrasubstituted naphthalene diimide compounds with N-methylpiperazine end groups has been synthesized and evaluated as G-quadruplex ligands. They have high affinity and selectivity for telomeric G-quadruplex DNA over duplex DNA. CD studies show that they induce formation of a parallel G-quadruplex topology. They inhibit the binding of hPOT1 and topoisomerase IIIα to telomeric DNA and inhibit telomerase activity in MCF7 cells. The compounds have potent activity in a panel of cancer cell lines, with typical IC50 values of ∼0.1μM, and up to 100-fold lower toxicity in a normal human fibroblast cell line.

A crystallographic and modelling study of a human telomeric RNA (TERRA) quadruplex

DNA telomeric repeats in mammalian cells are transcribed to guanine-rich RNA sequences, which adopt parallel-stranded G-quadruplexes with a propeller-like fold. The successful crystallization and structure analysis of a bimolecular human telomeric RNA G-quadruplex, folded into the same crystalline environment as an equivalent DNA oligonucleotide sequence, is reported here. The structural basis of the increased stability of RNA telomeric quadruplexes over DNA ones and their preference for parallel topologies is described here. Our findings suggest that the 2′-OH hydroxyl groups in the RNA quadruplex play a significant role in redefining hydration structure in the grooves and the hydrogen bonding networks. The preference for specific nucleotides to populate the C3′-endo sugar pucker domain is accommodated by alterations in the phosphate backbone, which leads to greater stability through enhanced hydrogen bonding networks. Molecular dynamics simulations on the DNA and RNA quadruplexes are consistent with these findings. The computations, based on the native crystal structure, provide an explanation for RNA G-quadruplex ligand binding selectivity for a group of naphthalene diimide ligands as compared to the DNA G-quadruplex.

Abstract 3679: Targeting drug-resistant GIST cells with a quadruplex-binding small molecule

Abstract Gastrointestinal tumours (GIST) originate, at least in part, from disregulation and consequent aberrant expression of the c-kit oncogene. Imatinib is an effective inhibitor of the ATP-binding activity of the kinase domain in the c-kit protein, and is used clinically to treat GIST patients. However acquired resistance to Imatinib is a severe problem hindering long-term patient survival. We have previously reported on an alternative approach to c-kit therapy that involves targeting and stabilising quadruplex DNA sequences with a small molecule, (i) in two sequences within the c-kit promoter so that c-kit expression is down-regulated, and (ii) in the single-stranded overhang of telomeric DNA, inhibiting telomerase activity in GIST cells. We have previously reported that both of these are targeted by a potent (IC50 ≪ 1μM) tetra-substituted naphthalene diimide compound in the Imatinib-sensitive GIST882 patient-derived cell line. This compound is equally potent in the patient-derived GIST48 Imatinib-resistant line; we report here that it has no effect on c-kit expression, telomerase activity, or the expression of other oncogenes in which promoter quadruplexes have been identified. Instead we find that the translation of the apoptosis-related bcl-2 gene is profoundly affected, but not its transcription. The bcl-2 gene has a potential quadruplex-forming region in the 5′-UTR sequence, and we report here that this forms a stable RNA quadruplex structure, which is further stabilised by the binding of the naphthalene diimide ligand. A reporter assay approach using a dual luciferase psiCHECK-2 vector, containing the bcl-2 5′-UTR sequence, is being used to validate the key concept that this G-rich sequence is involved in modulating translation in vitro, and in vivo through transfection into mammalian cells. Our current experiments in an Imatinib-resistant GIST cell line in the presence of the compound are enabling us to substantiate this cellular target and characterize the mode of action. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3679.

Synergistic metal and anion effects on the formation of coordination assemblies from a N,N′-bis(3-pyridylmethyl)naphthalene diimide ligand

Download options Please wait... Supplementary files Crystal structure data CIF (109K) XRD patterns for complexes 2, 4 and 5 PDF (387K) Crystal structure data TXT (109K) Article information DOI https://doi.org/10.1039/B819608G Article type Paper Submitted 04 Nov 2008 Accepted 12 Jan 2009 First published 07 Feb 2009 Download Citation CrystEngComm, 2009,11, 909-917 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Synergistic metal and anion effects on the formation of coordination assemblies from a N,N′-bis(3-pyridylmethyl)naphthalene diimide ligand H. Deng, J. He, M. Pan, L. Li and C. Su, CrystEngComm, 2009, 11, 909 DOI: 10.1039/B819608G To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Social activity Tweet Share Search articles by author Hai-Ying Deng Jian-Rong He Mei Pan Lei Li Cheng-Yong Su