In situ Electrochemical Small-Angle Neutron Scattering (<i>e</i>SANS) for Quantitative Structure and Redox Properties of Nanoparticles

The rapid growth in nanomaterial applications have revealed limitations in available physicochemical characterization methods. An in situ electrochemical small-angle neutron scattering (eSANS) methodology was devised that enables direct measurements of nanomaterial dispersion structure while undergoing reduction–oxidation (redox) reactions at the vitreous carbon electrode. Furthermore, these porous electrodes are amenable to contrast-variant neutron scattering strategies to measure nanoparticle structure and polymer conformation in multicomponent systems. The eSANS method was tested for feasibility by characterizing ZnO nanoparticles in 50 mmol/L NaCl deuterium oxide solution undergoing bulk electrolysis at negative potentials. Irreversible nanoparticle structural changes are observed during the potential cycle. The complete reduction of Zn²⁺ to Zn⁰ nanoparticles is unlikely, but a peak in the characteristic correlation length occurs during the redox bias with reduced average characteristic size

Self-Assembly and Dynamics Driven by Oligocarbonate–Fluorene End-Functionalized Poly(ethylene glycol) ABA Triblock Copolymers

The closed assembly transition from polymers to micelles and open assembly to clusters are induced by supramolecular π–π stacking in model oligocarbonate–fluorene (F-TMC) end-group telechelic polymers. The critical micelle concentration (CMC) depends on the F-TMC degree of polymerization that further controls the weak micelle association and strong clustering of micelles regimes. Clustering follows a multistep equilibria model with average size scaling with concentration reduced by the CMC as <i>R</i> ∼ (<i>c</i>/CMC)^1/4. The F-TMC packing that drives the supramolecular self-assembly from polymers to micelles stabilizes these larger clusters. The clusters are characterized by internal relaxations by dynamic light scattering. This signifies that while F-TMC groups drive the clustering, the micelles interconnected via F-TMC bridging interactions remain coupled to the extent that the clusters relax via Rouse–Zimm dynamics, reminiscent of microgels

Fabrication and Characterization of Hybrid Stealth Liposomes

Next-generation liposome systems for anticancer and therapeutic delivery require the precise insertion of stabilizing polymers and targeting ligands. Many of these functional macromolecules may be lost to micellization as a competing self-assembly landscape. Here, hybrid stealth liposomes, which utilize novel cholesteryl-functionalized block copolymers as the molecular stabilizer, are explored as a scalable platform to address this limitation. The employed block copolymers offer resistance to micellization through multiple liposome insertion moieties per molecule. A combination of thermodynamic and structural investigations for a series of hybrid stealth liposome systems suggests that a critical number of cholesteryl moieties per molecule defines whether the copolymer will or will not insert into the liposome bilayer. Colloidal stability of formed hybrid stealth liposomes further corroborates the critical copolymer architecture value

Formation of Disk- and Stacked-Disk-like Self-Assembled Morphologies from Cholesterol-Functionalized Amphiphilic Polycarbonate Diblock Copolymers

A cholesterol-functionalized aliphatic cyclic carbonate monomer, 2-(5-methyl-2-oxo-1,3-dioxane-5-carboxyloyloxy)­ethyl carbamate (MTC-Chol), was synthesized. The organocatalytic ring-opening polymerization of MTC-Chol was accomplished by using <i>N</i>-(3,5-trifluoromethyl)­phenyl-<i>N</i>′-cyclohexylthiourea (TU) in combinations with bases such as 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU) and (−)-sparteine, and kinetics of polymerization was monitored. By using mPEG-OH as the macroinitiator, well-defined amphiphilic diblock copolymers mPEG₁₁₃-<i>b</i>-P­(MTC-Chol)_<i>n</i> (<i>n</i> = 4 and 11) were synthesized. Under aqueous conditions, these block copolymers self-assembled to form unique nanostructures. Disk-like micelles and stacked-disk morphology were observed for mPEG₁₁₃-<i>b</i>-P­(MTC-Chol)₄ and mPEG₁₁₃-<i>b</i>-P­(MTC-Chol)₁₁, respectively, by transmission electron microscopy (TEM). Small-angle neutron scattering supports the disk-like morphology and estimates the block copolymer micelle aggregation number in the dispersed solution. The hydrophobic nature of the cholesterol-containing block provides a versatile self-assembly handle to form complex nanostructures using biodegradable and biocompatible polymers for applications in drug delivery

Spatial Distribution of Hydrophobic Drugs in Model Nanogel-Core Star Polymers

Star polymers with a cross-linked nanogel core are promising carriers of cargo for therapeutic applications due to the synthetic control of amphiphilicity of arms and stability at infinite dilution. Three nanogel-core star polymers were investigated to understand how the arm-block chemical structure controls loading efficiency of a model drug, ibuprofen, and its spatial distribution. The spatial distribution profiles of hydrophobic core, hydrophilic corona, and encapsulated drug were determined by small-angle neutron scattering (SANS). SANS provides the nanometer-scale sensitivity to determine how the arm-block chemistry enhances the sequestering of ibuprofen. Validated molecular dynamics simulations capture the trends in drug profile and polymer segment distribution with further details on drug orientation distribution. This work provides a basis to study structure–function relationships in macromolecular-based carriers of cargo and represents a path toward validated and predictive simulation

pH-Sensitive Compounds for Selective Inhibition of Acid-Producing Bacteria

Stimuli-responsive compounds that provide on-site, controlled antimicrobial activity promise an effective approach to prevent infections, reducing the need for systemic antibiotics. We present a novel pH-sensitive quaternary pyridinium salt (QPS), whose antibacterial activity is boosted by low pH and controlled by adjusting the pH between 4 and 8. Particularly, this compound selectively inhibits growth of acid-producing bacteria within a multispecies community. The successful antibacterial action of this QPS maintains the environmental pH above 5.5, a threshold pH, below which demineralization/erosion takes place. The design, synthesis, and characterization of this QPS and its short-chain analogue are discussed. In addition, their pH-sensitive physicochemical properties in aqueous and organic solutions are evaluated by UV–vis spectroscopy, dynamic light scattering, and NMR spectroscopy. Furthermore, the mechanism of action reveals a switchable assembly that is triggered by acid–base interaction and formed by tightly stacked π-conjugated systems and base moieties. Finally, a model is proposed to recognize the correlated but different mechanisms of pH sensitivity and acid-induced, pH-controlled antibacterial efficacy. We anticipate that successful application of these QPSs and their derivatives will provide protections against infection and erosion through targeted treatments to acid-producing bacteria and modulation of environmental pH