No abstract

As demonstrated by means of DNA nanoconstructs[1], as well as DNA functionalization of nanoparticles[2-4] and micrometre-scale colloids[5-8], complex self-assembly processes require components to associate with particular partners in a programmable fashion. In many cases the reversibility of the interactions between complementary DNA sequences is an advantage[9]. However, permanently bonding some or all of the complementary pairs may allow for flexibility in design and construction[10]. Here, we show that the substitution of a pair of complementary bases by a cinnamate group provides an efficient, addressable, UV light-based method to covalently bond complementary DNA. To show the potential of this approach, we wrote micrometre-scale patterns on a surface via UV light and demonstrate the reversible attachment of conjugated DNA and DNA-coated colloids. Our strategy enables both functional DNA photolithography and multi-step, specific binding in self-assembly processes.

Rigid macrocycles 2, which share a hybrid backbone and the same set of side chains while having inner cavities with different inward-pointing functional groups, undergo similar nanotubular assembly as indicated by multiple techniques including (1)H NMR, fluorescence spectroscopy, and atomic force microscopy. The formation of tubular assemblies containing subnanometer pores is also attested by the different transmembrane ion-transport behavior observed for these macrocycles. Vesicle-based stopped-flow kinetic assay and single-channel electrophysiology with planar lipid bilayers show that the presence of an inward-pointing functional (X) group in the inner cavity of a macrocyclic building block exerts a major influence on the transmembrane ion-transporting preference of the corresponding self-assembling pore. Self-assembling pores with inward-pointing amino and methyl groups possess the surprising and remarkable capability of rejecting protons but are conducive to transporting larger ions. The inward-pointing groups also resulted in transmembrane pores with a different extent of positive electrostatic potentials, leading to channels having different preferences for transporting chloride ion. Results from this work demonstrate that synthetic modification at the molecular level can profoundly impact the property of otherwise structurally persistent supramolecular assemblies, with both expected tunability and suprisingly unusual behavior.

[structures: see text] This article describes the synthetic procedures for the preparation of crescent (and helical) aromatic oligoamides developed in recent years in our laboratory. The large-scale preparation of a variety of monomers derived from various tetrasubstituted benzenes is presented. Three different strategies for constructing various oligomers consisting of meta- and meta/para-linked benzene residues are discussed. Factors affecting coupling efficiency and yields are analyzed. The developed synthetic methods have provided the basis for the preparation of longer oligomers and for the development of solid-phase synthesis.

This article describes an associating system that integrates the specificity of multiple hydrogen bonding and the strength of dynamic covalent interactions. Linear oligoamides that sequence-specifically pair into H-bonded duplexes in nonpolar solvents were modified with S-trityl groups, allowing the reversible formation of disulfide bonds. The disulfide-crosslinking reactions of oligoamides capable of pairing via two, four, and six intermolecular H-bonds, along with several control strands, were examined using ESI, MALDI-TOF, reverse phase HPLC, and two-dimensional NMR. Results from these studies demonstrate that this system possesses both the high fidelity of multiply H-bonded assemblies and the high stability of covalent interaction, leading to the sequence-specific crosslinking of complementary oligoamides in not only nonpolar (methylene chloride) solutions but also highly competitive (aqueous) media. Experiments were designed to systematically probe the mechanism behind the specific formation of the sequence-matched products, which revealed a thermodymically controlled process. Multiple pairs in the same solution were crosslinked in a sequence-specific fashion. In addition, a length-dependent selectivity was also observed. Thus, oligoamides with different lengths or sequences did not crosslink into mismatched products. As few as two H-bonds is sufficient to bias the specific formation of the crosslinked product in aqueous media, suggesting that associating units with tunable sizes, high stability, and high specificity can be conveniently designed. The combination of H-bonding and dynamic covalent interactions represents a new, generalizable strategy for developing highly specific molecular associating units that are stable in a wide variety of media. These associating units will greatly facilitate the construction of various structures with many applications.

Oligoamide strands that associate in a sequence-specific fashion into hydrogen-bonded duplexes in nonpolar solvents were converted into disulfide cross-linked duplexes in aqueous media. Thus, by incorporating trityl-protected thiol groups, which allows the reversible formation of disulfide bonds, into the oligoamide strands, only duplexes consisting of complementary hydrogen-bonding sequences were formed in aqueous solution as well as in methanol. The sequence-specific cross-linking of oligoamide strands was confirmed by MALDI-TOF, reverse-phase HPLC, and by isolating a cross-linked duplex. This study demonstrates that the sequence-specificity characteristic of multiply hydrogen-bonded systems can be extended into competitive media through the interplay of H-bonding and reversible covalent interactions, based on which a new class of molecular associating and ligating units that are compatible with both polar and nonpolar environments can be conveniently obtained.

A rationally designed small-molecule fluorogenic probe for nitric oxide (NO) detection based on a new switching mechanism has been developed. Attaching a NO-responsive dihydropyridine pendant group to a fluorophore led to a probe that displays a very high sensitivity to NO concentrations down to the low nM range and a very high specificity to NO while being insensitive to other oxidative oxygen/nitrogen species that often interfere with the sensing of NO.

Highly stable and polymerizable δ-valerolactones bearing oligo-(ethylene glycol) methyl ether functionalities are facilely prepared by alkylphosphine catalyzed thiol-ene addition with an exocyclic α,β-unsaturated δ-valerolactone. The functionalized lactones undergo efficient ring-opening polymerization (ROP) to afford well defined PEG-like polyesters. Kinetic studies revealed that the ROP, catalyzed by diphenyl phosphate at ambient temperature, shows living nature. The results of cell viability assays indicate that the resultant polyesters are fully biocompatible. In vitro tests on protein adsorption and cell adhesion demonstrate that the antifouling capability of these polyesters is comparable to that of PEG.The strategy for facile preparation of stable and polymerizable lactones bearing functional substituents reported here provides a versatile platform for the development of polyester-based new biocompatible and biodegradable polymeric materials for biomedical applications.Poly(ethylene glycol) (PEG) is a neutral, hydrophilic, and biocompatible polyether that is widely adopted in biomedical applications. PEG is well known as one of the most effective synthetic polymers in reducing non-specific protein adsorption. 1,2 PEGylation has also been extensively exploited on a wide variety of chemical and biomedical entities, including small drugs and pharmaceutical carriers, in order to enhance their biomedical efficacy and physicochemical properties. 3 In fact, PEG is the only synthetic polymer approved by the Food and Drug Administration (FDA) for preparing polymer-protein conjugates. 4,5 However, with the rapidly growing interest in protein-based therapeutics, 6 the inherent nonbiodegradability of PEGs, as one of the major drawbacks, has caused increasing concern. 7,8 High-molecular-weight (high-M w ) PEGs (over 40 kDa) are metabolically inert, with their excretion rates being significantly reduced. 9 Recently, an increasing number of reports have shown that high-M w PEGs can accumulate and cause vacuolation in the liver, kidney, spleen and tissues after administration. 7b-e,10 Growing concern on bioaccumulation and cytoplasmic vacuolization issues of PEG prompted a search for solutions to overcome its limitation of non-biodegradability. One solution is to incorporate cleavable moieties into the backbone of PEG based on step-growth polymerization. 11,12 However, the linear PEG-analogues offered by these approaches are usually not well defined. Many biomedical applications, especially the in vivo ones, would benefit from synthetic polymeric materials with well defined structures (e.g. narrow polydispersity, PDI). 13 Well defined polymethacrylates with cleavable pendant oligomeric poly(ethylene oxide) (PEO) side chains as degradable PEG analogues have been synthesized via controlled radical polymerization, 14-17 but their non-biodegradable carboncarbon backbones could limit their in vivo applications as biomedical materials. 18 Aliphatic poly(ester)s, on the other hand, offer backbones that are biocompatible and bio...