Janus and Amphiphilic MoS2 2D Sheets for Surface-Directed Orientational Assemblies toward Ex Vivo Dual Substrate Release.

The two-dimensional (2-D) Janus and amphiphilic molybdenum disulfide (MoS2) nanosheet with opposite optical activities on each side (amphichiral) is synthesized by modifying sandwich-like bulk MoS2 with tannic acid and cholesterol through biphasic emulsion method. This new type of amphichiral Janus MoS2 nanosheet consists of a hydrophilic and positive optical activity tannic acid side as well as a hydrophobic and negative optical activity cholesterol side thereby characterized by circular dichroism. Surface-directed orientational differentiation assemblies are performed for the as-synthesized 2D material and are characterized by contact angle, infrared spectroscopy, X-ray photoelectron, and circular dichroism spectroscopies. The amphiphilic nature of the materials is demonstrated by the pre-organization of the nanosheets on either hydrophobic or hydrophilic surfaces, providing unprecedented properties of circular dichroism signal enhancement and wettability. Selective detachment of the surface organic groups (cholesterol and tannic acid fragments) is realized by matrix-assisted laser desorption/ionisation - time-of-flight (MALDI-TOF) mass spectrometry, and the dual substrate release in tissue is detected by ex vivo mass spectrometry imaging.

One-Pot Preparation of Cetylpyridinium Chloride-Containing Nanoparticles for Biofilm Eradication.

Quaternary ammonium compounds (QACs) have been widely used due to their excellent antimicrobial activity. However, using the technology where nanomaterials are employed as drug carriers to deliver QAC drugs has not been fully explored. In this study, mesoporous silica nanoparticles (MSNs) with short rod morphology were synthesized in a one-pot reaction using an antiseptic drug cetylpyridinium chloride (CPC). CPC-MSN were characterized via various methods and tested against three bacterial species (Streptococcus mutans, Actinomyces naeslundii, and Enterococcus faecalis), which are associated with oral infections, caries, and endodontic pathology. The nanoparticle delivery system used in this study prolonged the release of CPC. The manufactured CPC-MSN effectively killed the tested bacteria within the biofilm, and their size allowed them to penetrate into dentinal tubules. This CPC-MSN nanoparticle delivery system demonstrates potential for applications in dental materials.

Synthesis of Functional Building Blocks for Type III-B Rotaxane Dendrimer.

Second-generation type III-B rotaxane dendrons, equipped with succinimide and acetylene functional groups, were synthesized successfully and characterized by NMR spectroscopy and mass spectrometry. A cell viability study of a dendron with a normal cell line of L929 fibroblast cells revealed no obvious cytotoxicity at a range of 5 to 100 µM. The nontoxic properties of the sophisticated rotaxane dendron building blocks provided a choice of bio-compatible macromolecular machines that could be potentially developed into polymeric materials.

π-Stacking Stopper-Macrocycle Stabilized Dynamically Interlocked [2]Rotaxanes.

The synthesis of mechanically interlocked molecules is valuable due to their unique topologies. With π-stacking intercomponent interaction, e.g., phenanthroline and anthracene, novel [2]rotaxanes have been synthesized by dynamic imine clipping reaction. Their X-ray crystal structures indicate the π-stackings between the anthracene moiety (stopper) on the thread and the (hetero)aromatic rings at the macrocycle of the rotaxanes. Moreover, the length of glycol chains affects the extra π-stacking intercomponent interactions between the phenyl groups and the dimethoxy phenyl groups on the thread. Dynamic combinatorial library has shown at best 84% distribution of anthracene-threaded phenanthroline-based rotaxane, coinciding with the crystallography in that the additional π-stacking intercomponent interactions could increase the thermodynamic stability and selectivity of the rotaxanes.

Design and Synthesis of Mucin-Inspired Glycopolymers.

Mucins are bottlebrush biopolymers that are glycoproteins on the surfaces of cells and as hydrogels secreted inside and outside the body. Mucin function in biology includes cell-cell recognition, signaling, protection, adhesion, and lubrication. Because of their attractive and diverse properties, mucins have recently become the focus of synthetic efforts by researchers who hope to understand and emulate these biomaterials. This review is focused on the development of methodologies for preparing mucin-inspired synthetic oligomers and glycopolymers, including solid-phase synthesis, polymerization of glycosylated monomers, and post-polymerization grafting of glycans to polymer chains. How these synthetic mucins have been used in health applications is discussed. Natural mucins are formed from a conserved set of monomers that are combined into chains of different sequences and lengths to achieve materials with widely diverse properties. Adopting this design paradigm from natural mucins could lead to next-generation bioinspired synthetic materials.

MALDI-MS Imaging Analysis of Noninflammatory Type III Rotaxane Dendrimers.

Rotaxane dendrimers with hyperbranched macromolecular interlocked structures and size modulation capacity demonstrate drug binding and release ability upon external stimuli. Mass spectrometry imaging (MSI) can offer the high-throughput screening of endogenous/exogenous compounds. Herein, we reported a novel method to display the in situ spatial distribution of label-free monodispersed type III rotaxane dendrimers (RDs) G1 (first generation, size ∼1.5 nm) and G2 (second generation, size ∼5 nm) that were explored as potential drug vehicles in spleen tissue by using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-MSI). Experimental results indicated that the trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile (DCTB) matrix exhibited the best performance for monodispersed type III RDs G1 and G2. The optimized method was successfully applied to map the in vivo spatial distribution of type III RDs G1 and G2 in the spleen from intraperitoneally injected mice. The MALDI-MSI images revealed that RDs G1 and G2 were relatively stable in the spleen within 24 h after administration. It was found that the identified type III RDs G1 and G2 penetrated through the tunica serosa and were predominantly localized in red pulp regions of spleens. They were also mapped in a marginal zone of spleens simultaneously. There was almost no toxicity of type III RDs G1 and G2 to mice spleens from the H&E results. Furthermore, the type III RDs did not induce the expression of inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) or THP-1 monocytes. The MSI analysis not only demonstrated its ability to image select rotaxane dendrimers in a rapid and efficient manner but also provided tremendous assistance on the applications of the further treatment of cancerous tissue as safe drug carriers. Furthermore, the new strategy demonstrated in this study could be applied on other label-free mechanically interlocked molecules, molecular machines, and macromolecules, which opened a new path to evaluate the toxicological and pharmacokinetic characteristics of these novel materials at the suborgan level.

Selective detection of sulfide in human lung cancer cells with a blue-fluorescent "ON-OFF-ON" benzimidazole-based chemosensor ensemble.

A completely water-soluble, high quantum yield blue-fluorescent benzimidazole derivative (AQ), containing a rigid benzimidazole-thiophene structure, was synthesized. Among 21 metal ions, the fluorescence of AQ was selectively turned off by Cu2+ to form an AQ-Cu2+ ensemble. Thereafter, the fluorescence of the AQ-Cu2+ ensemble was turned on by sulfide (S2-) with high selectivity and sensitivity in pure water solution. In comparison with AQ-Ag+ and AQ-Hg2+ ensembles, AQ-Cu2+ was the only ensemble that was capable of detecting a sulfide anion. Also, the fluorescence intensity of AQ was linearly proportional to the concentration of Cu2+ and S2-. Both Cu2+ and S2- were detected within a minute in vitro. Moreover, AQ worked best in the pH range of 5-10 and had a limit of detection of 50 nM and 354 nM for Cu2+ and S2- respectively. It was employed for the detection of sulfide in human lung cancer A549 cells with low cytotoxicity.

Highly selective detection of Pd2+ ion in aqueous solutions with rhodamine-based colorimetric and fluorescent chemosensors.

In this study, we report a new class of rhodamine-based fluorescent sensors for highly selective and sensitive detection of Pd2+ ions in aqueous medium. A rhodamine-based palladium sensor RPS and a coumarin-rhodamine Förster resonance energy transfer (FRET)-pair based palladium sensor FPS were synthesized with the designed podand ligand for Pd2+ ion recognition. They showed both colorimetric change and fluorometric change in the presence of Pd2+ ion due to the opening of their spirolactam rings. Both chemosensors are highly selective to Pd2+ over the other 24 different metal ions and they are selective to palladium species in +2 oxidation state, RPS showed a 70-fold fluorescent turn-on while FPS showed a 1.75-fold ratiometric change at I599/I470. Furthermore, RPS showed low cell cytotoxicity and it was successfully used to image Pd2+ in BEAS-2B lung epithelial cells. © 2019 Elsevier Science. All rights reserved.

Type III-C rotaxane dendrimers: synthesis, dual size modulation and in vivo evaluation.

Type III-C rotaxane dendrimers were synthesized by a divergent approach. Dual shuttling behavior and size modulation were observed from non-methylated/methylated rotaxane dendrimers under the same external stimuli. The biological distribution of dendrimers in C57BL/6J mice determined by MALDI-TOF-MS shows predominant accumulation in the spleen and liver. Drug encapsulations with chlorambucil and lithocholic acid were demonstrated.

Higher-generation type III-B rotaxane dendrimers with controlling particle size in three-dimensional molecular switching.

Type III-B rotaxane dendrimers (T3B-RDs) are hyperbranched macromolecules with mechanical bonds on every branching unit. Here we demonstrate the design, synthesis, and characterization of first to third (G1-G3), and up to the fourth (G4) generation (MW > 22,000 Da) of pure organic T3B-RDs and dendrons through the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. By utilizing multiple molecular shuttling of the mechanical bonds within the sphere-like macromolecule, a collective three-dimensional contract-extend molecular motion is demonstrated by diffusion ordered spectroscopy (DOSY) and atomic force microscopy (AFM). The discrete T3B-RDs are further observed and characterized by AFM, dynamic light scattering (DLS), and mass spectrometry (MS). The binding of chlorambucil and pH-triggered switching of the T3B-RDs are also characterized by 1H-NMR spectroscopy.

A Fluorescent and Switchable Rotaxane Dual Organocatalyst.

Rotaxane organocatalysis presents a new direction toward controlled one-pot catalytic reactions. By combining molecular switches and catalysts, fluorescence and pH-responsive switching along with the exclusive selectivity of dual catalytic reactions are demonstrated. A newly designed [2]rotaxane catalyst containing an anthracene group was used to visualize the catalytic reaction process upon switching the macrocycle.

Type III-B rotaxane dendrimers.

Type III-B first generation [3]rotaxane and second generation [4]rotaxane dendrimers have been synthesized via (1) a modified copper-catalyzed alkyne-azide cycloaddition (CuAAC), (2) Glaser-Hay's acetylenic oxidative homo-coupling, and (3) amide formation. The dendron does not reveal obvious cytotoxicities in L929 fibroblast cells. The rotaxane dendrimers can capture ammonia and are switchable both in solution and on surfaces.