Reactions of Brominated Naphthalene Diimide with Bis(tributylstannyl)acetylene: A Simple Approach for Conjugated Polymers and Versatile Coupling Intermediates

A new synthetic approach to 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) containing materials and conjugates is described. A simple one-step Stille coupling procedure is used to create either novel alkyne-linked NDI polymers or a new stannylated diyne synthetic building block that provides a flexible approach to new NDI conjugates and polymers

Threading Polyintercalators with Extremely Slow Dissociation Rates and Extended DNA Binding Sites

The development of small molecules that bind DNA sequence specifically has the potential to modulate gene expression in a general way. One mode of DNA binding is intercalation, or the insertion of molecules between DNA base pairs. We have developed a modular polyintercalation system in which intercalating naphthalene diimide (NDI) units are connected by flexible linkers that alternate between the minor and major grooves of DNA when bound. We recently reported a threading tetraintercalator with a dissociation half-life of 16 days, the longest reported to date, from its preferred 14 bp binding site. Herein, three new tetraintercalator derivatives were synthesized with one, two, and three additional methylene units in the central major groove-binding linker. These molecules displayed dissociation half-lives of 57, 27, and 18 days, respectively, from the 14 bp site. The optimal major groove-binding linker was used in the design of an NDI hexaintercalator that was analyzed by gel-shift assays, DNase I footprinting, and UV–vis spectroscopy. The hexaintercalator bound its entire 22 bp binding site, the longest reported specific binding site for a synthetic, non-nucleic acid-based DNA binding molecule, but with a significantly faster dissociation rate compared to the tetraintercalators

NDI and DAN DNA: Nucleic Acid-Directed Assembly of NDI and DAN

Two novel DNA base surrogate phosphoramidites <b>1</b> and <b>2</b>, based upon relatively electron-rich 1,5-dialkoxynaphthalene (DAN) and relatively electron-deficient 1,4,5,8-naphthalenetetracarboxylic diimide (NDI), respectively, were designed, synthesized, and incorporated into DNA oligonucleotide strands. The DAN and NDI artificial DNA bases were inserted within a three-base-pair region within the interior of a 12-mer oligonucleotide duplex in various sequential arrangements and investigated with CD spectroscopy and UV melting curve analysis. The CD spectra of the modified duplexes indicated B-form DNA topology. Melting curve analyses revealed trends in DNA duplex stability that correlate with the known association of DAN and NDI moieties in aqueous solution as well as the known favorable interactions between NDI and natural DNA base pairs. This demonstrates that DNA duplex stability and specificity can be driven by the electrostatic complementarity between DAN and NDI. In the most favorable case, an NDI–DAN–NDI arrangement in the middle of the DNA duplex was found to be approximately as stabilizing as three A–T base pairs

Time-Dependent Solid-State Polymorphism of a Series of Donor–Acceptor Dyads

In order to exploit the use of favorable electrostatic interactions between aromatic units in directing the assembly of donor–acceptor (D–A) dyads, the present work examines the ability of conjugated aromatic D–A dyads with symmetric side chains to exhibit solid-state polymorphism as a function of time during the solid formation process. Four such dyads were synthesized, and their packing in the solid state from either slower (10–20 days) or faster (1–2 days) evaporation from solvent was investigated using single crystal X-ray analysis and powder X-ray diffraction. Two of the dyads exhibited tail-to-tail (A–A) packing upon slower evaporation from solvent and head-to-tail (D–A) packing upon faster evaporation from solvent. A combination of single-crystal analysis and XRD patterns were used to create models, wherein a packing model for the other two dyads is proposed. Our findings suggest that while side chain interactions in asymmetric aromatic dyads can play an important role in enforcing segregated D–A dyad assembly, slowly evaporating symmetrically substituted aromatic dyads allows for favorable electrostatic interactions between the aromatic moieties to facilitate the organization of the dyads in the solid state

Time-Dependent Solid-State Polymorphism of a Series of Donor–Acceptor Dyads

In order to exploit the use of favorable electrostatic interactions between aromatic units in directing the assembly of donor–acceptor (D–A) dyads, the present work examines the ability of conjugated aromatic D–A dyads with symmetric side chains to exhibit solid-state polymorphism as a function of time during the solid formation process. Four such dyads were synthesized, and their packing in the solid state from either slower (10–20 days) or faster (1–2 days) evaporation from solvent was investigated using single crystal X-ray analysis and powder X-ray diffraction. Two of the dyads exhibited tail-to-tail (A–A) packing upon slower evaporation from solvent and head-to-tail (D–A) packing upon faster evaporation from solvent. A combination of single-crystal analysis and XRD patterns were used to create models, wherein a packing model for the other two dyads is proposed. Our findings suggest that while side chain interactions in asymmetric aromatic dyads can play an important role in enforcing segregated D–A dyad assembly, slowly evaporating symmetrically substituted aromatic dyads allows for favorable electrostatic interactions between the aromatic moieties to facilitate the organization of the dyads in the solid state

Subtle Recognition of 14-Base Pair DNA Sequences via Threading Polyintercalation

Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading polyintercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator composed of alternating minor–major–minor groove-binding modules was shown to bind specifically to a 14 bp DNA sequence with a dissociation half-life of 16 days [Holman, G. G., et al. (2011) <i>Nat. Chem. 3</i>, 875–881]. Herein are described new NDI-based tetraintercalators with a different major groove-binding module and a reversed N to C directionality of one of the minor groove-binding modules. DNase I footprinting and kinetic analyses revealed that these new tetraintercalators are able to discriminate, by as much as 30-fold, 14 bp DNA binding sites that differ by 1 or 2 bp. Relative affinities were found to correlate strongly with dissociation rates, while overall <i>C</i>₂ symmetry in the DNA-binding molecule appeared to contribute to enhanced association rates