Fighting Aggregation‐Caused Quenching and Leakage of Dyes in Fluorescent Polymer Nanoparticles: Universal Role of Counterion

Dye‐loaded polymer nanoparticles (NPs) emerge as a powerful tool for bioimaging applications, owing to their exceptional brightness and controlled small size. However, aggregation‐caused quenching (ACQ) and leakage of dyes at high loading remain important challenges of these nanomaterials. The use of bulky hydrophobic counterions has been recently proposed as an effective approach to minimize ACQ and dye leakage, but the role of counterion structure is still poorly understood. Here, a systematic study based on ten counterions, ranging from small hydrophilic perchlorate up to large hydrophobic tetraphenylborate derivatives, reveals how counterion nature can control encapsulation and emission of a cationic dye (rhodamine B octadecyl ester) in NPs prepared by nanoprecipitation of a biodegradable polymer, poly‐lactide‐co‐glycolide (PLGA). We found that increase in counterion hydrophobicity enhances dye encapsulation efficiency and prevents dye adsorption at the particle surface. Cellular imaging studies revealed that ≥95 % encapsulation efficiency, achieved with most hydrophobic counterions (fluorinated tetraphenylborates), is absolutely required because non‐encapsulated dye species at the surface of NPs are the origin of dye leakage and strong fluorescence background in cells. The size of counterions is found to be essential to prevent ACQ, where the largest species, serving as effective spacer between dyes, provide the highest fluorescence quantum yield. Moreover, we found that the most hydrophobic counterions favor dye–dye coupling inside NPs, leading to ON/OFF fluorescence switching of single particles. By contrast, less hydrophobic counterions tend to disperse dyes in the polymer matrix favoring stable emission of NPs. The obtained structure‐property relationships validate the counterion‐based approach as a mature concept to fight ACQ and dye leakage in the development of advanced polymeric nanomaterials with controlled optical properties.     

Scaling Theory of Strongly Charged Cylindrical Polyelectrolyte Brushes

Scaling theory of charged cylindrical polyelectrolyte brushes is developed. The dependence of brush thickness on the grafting density, charge fraction, and chain length is analyzed. A full phase diagram is established. Characteristics and boundaries between different regimes of cylindrical polyelectrolyte brushes are summarized. Special attentions are paid to electrostatic interaction induced stiffening and counterion condensation effects. If the Bjerrum length of the solution is larger than the Kuhn length of the polyelectrolyte chains, counterion condensation occurs in the strongly charged polyelectrolyte brushes. On the contrary, the electrostatic interaction stretches the strongly charged grafted polyelectrolyte chains to their contour length.     

Preparation of AgBr Nanoparticles in Microemulsions Via Reaction of AgNO<Subscript>3</Subscript> with CTAB Counterion

Nanoparticles of AgBr were prepared by precipitating AgBr in the water pools of microemulsions consisting of CTAB, n-butanol, isooctane and water. An aqueous solution of AgNO₃ added to the microemulsion was the source of Ag⁺ ions. The formation of AgBr nanoparticles in microemulsions through direct reaction with the surfactant counterion is a novel approach aimed at decreasing the role of intermicellar nucleation on nanoparticle formation for rapid reactions. The availability of the surfactant counterion in every reverse micelle and the rapidity of the reaction with the counterion trigger nucleation within individual reverse micelles. The effect of the following variables on the particle size and size distribution was investigated: the surfactant and cosurfactant concentrations, moles of AgNO₃ added, and water to surfactant mole ratio, R. High concentration of the surfactant or cosurfactant, or high water content of the microemulsion favored intermicellar nucleation and resulted in the formation of large particles with broad size distribution, while high amounts of AgNO₃ favored nucleation within individual micelles and resulted in small nanoparticles with narrow size distribution. A blue shift in the UV absorption threshold corresponding to a decrease in the particle size was generally observed. Notably, the variation of the absorption peak size with the nanoparticle size was opposite to those reported by us in previous studies using different surfactants.     

Intriguing diaza effects on magnetic coupling characteristics in diaza‐benzo[k]tetraphene‐bridged nitroxide diradicals

We theoretically design four diaza‐benzo[k]tetraphene‐based diradical isomers ( 1, 2, 3 , and 4 ) with two nitroxide (NO) radical groups as spin sources. The calculations at the B3LYP/6‐311++G(d,p) level suggest that the diaza doping can induce the aromaticity changes and the C C bond rearrangements and, thus, remarkably affect their magnetic coupling magnitudes and even characteristics (ferromagnetic vs. antiferromagnetic). More interestingly, different diaza‐doping positions can lead to distinctly different effects, and further dielectron‐oxidation can also noticeably change the magnetic coupling magnitudes from −919.9 cm⁻¹ ( 1 ) to −158.3 cm⁻¹ ( 1 ²⁺ ) or from −105.1 cm⁻¹ ( 3 ) to −918.9 cm⁻¹ ( 3 ²⁺ ) or induce the magnetic conversions from nonmagnetism ( 2 ) to antiferromagnetism ( 2 ²⁺ , −140.1 cm⁻¹) or from ferromagnetism ( 4 , 108.9 cm⁻¹) to antiferromagnetism ( 4 ²⁺ , −462.5 cm⁻¹). Good matching of two singly occupied molecular orbitals (SOMOs) of the NO groups with the highest occupied molecular orbital (HOMO) of the coupler (for 1 ), or with the lowest unoccupied molecular orbital (LUMO) of the coupler (for 3 ²⁺ and 4 ²⁺ ), available Kekulé structure (for 2 ), aromaticity variations are responsible to strong magnetic couplings. Besides, the HOMO‐LUMO energy gaps of the couplers also considerably affect the magnetic couplings. This work may open a new route for the rational design of the diaza‐benzo[k]tetraphene‐based magnetic molecular modulators or switches.     

Thielavin B methyl ester: a cytotoxic benzoate trimer from an unidentified fungus (MSX 55526) from the Order Sordariales

As part of our ongoing investigation of filamentous fungi for anticancer leads, an active fungal extract was identified from the Mycosynthetix library (MSX 55526; from the Order Sordariales). Bioactivity-directed fractionation yielded the known ergosterol peroxide (2) and 5α,8α-epidioxyergosta-6,9(11),22-trien-3β-ol (3), and a new benzoate trimer, termed thielavin B methyl ester (1). The structure elucidation of 1 was facilitated by the use of HRMS coupled to an APPI (atmospheric pressure photoionization) source. Compound 1 proved to be moderately active against a panel of three cancer cell lines.     

Analysis of the Binding of Cytokines to Highly Charged Polymer Networks

A model describing the binding of biological signaling proteins to highly charged polymer networks is presented. The networks are formed by polyelectrolyte chains for which the distance between two charges at the chain is smaller than the Bjerrum length. Counterion condensation on such highly charged chains immobilizes a part of the counterions. The Donnan-equilibrium between the polymer network and the aqueous solution with salt concentration $c_s^b$ is used to calculate the salt concentration of the co- and counterions $c_s^g$ entering the network. Two factors are decisive: i) The electrostatic interaction between the network and the protein is given by the Donnan-potential of the network and the net charge of the protein. In addition to this leading term, a second term describes the change in the Born-energy of the proteins when entering the network. ii) The interaction of the protein with the highly charged chains within the network is governed by counterion release: Patches of positive charge at the protein become multivalent counterions of the polyelectrolyte chains thus releasing a concomitant number of condensed counterions. The model compares favorably to experimental data obtained on a set of biohybrid polymer networks composed of crosslinked glycosaminoglycan chains that interact with a mixture of key signaling proteins.     

Synthesis and properties in solution of rodlike polyelectrolytes

Efficient synthetic strategies are described for the preparation of rodlike polyelectrolytes based on the intrinsically rigid poly(p-phenylene). Uncharged precursors were first prepared via the Suzuki coupling and then characterized by different methods of polymer analysis. Finally, they were transformed into polyelectrolytes using macromolecular substitution reactions. Depending on the substitution pattern, the obtained polyelectrolytes are either soluble or insoluble in water. Using water-soluble derivatives, the Poisson-Boltzmann cell model was tested by osmotic measurements and small-angle X-ray scattering. It is shown that the cell model provides a good first approximation of the distribution of the counterions around the macroion but still underestimates their correlation. Moreover, the PPP polyelectrolytes show a very pronounced polyelectrolyte effect. Since the rodlike PPPs are very rigid in shape, this observation proves that the polyelectrolyte effect is caused by long-range intermolecular electrostatic repulsion of the dissolved macroions rather than due to conformational changes.     

Counterion mobility and effective charge of polyelectrolytes in solution

Polyelectrolytes are macromolecules containing dissociable or charged groups. The charge, that is effectively accessible, is determined by counterion condensation, which is strongly influenced by the ionic strength of the solution under study. In general a rapid exchange between free and condensed counterions is expected. In the present study diffusion and electrophoretic mobility of poly(diallyldimethylammoniumchloride) and perfluorinated succinic acid have been monitored simultaneously. Condensation of the perfluorinated succinic acid to the macroion shows in the electrophoretic mobility of succinic acid monitored by pulsed field gradient NMR. In the concentration dependence of the averaged diffusion coefficient and electrophoretic mobility an exchange fast on the time scale of the NMR experiment is manifested.