The self-assembly of metallacarboranes, a peculiar family of compounds exhibiting surface activity and resembling molecular-scale Pickering stabilizers, has been investigated by comparison to the micellization of sodium dodecylsulfate (SDS). These studies have shown that molecules without classical amphiphilic topology but with an inherent amphiphilic nature can behave similarly to classical surfactants. As shown by NMR techniques, the self-assembly of both metallacarboranes and SDS obey a closed association model. However, the aggregation of metallacarboranes is found to be enthalpy-driven, which is very unusual for classical surfactants. Possible explanations of this fact are outlined.

In this paper, we studied a designed series of aldose reductase (AR) inhibitors. The series was derived from a known AR binder, which had previously been shown to form a halogen bond between its bromine atom and the oxygen atom of the Thr-113 side chain of AR. In the series, the strength of the halogen bond was modulated by two factors, namely bromine-iodine substitution and the fluorination of the aromatic ring in several positions. The role of the single halogen bond in AR-ligand binding was elucidated by advanced binding free energy calculations involving the semiempirical quantum chemical Hamiltonian. The results were complemented with ultrahigh-resolution X-ray crystallography and IC50 measurements. All of the AR inhibitors studied were shown by X-ray crystallography to bind in an identical manner. Further, it was demonstrated that it was possible to decrease the IC50 value by about 1 order of magnitude by tuning the strength of the halogen bond by a monoatomic substitution. The calculations revealed that the protein-ligand interaction energy increased upon the substitution of iodine for bromine or upon the addition of electron-withdrawing fluorine atoms to the ring. However, the effect on the binding affinity was found to be more complex due to the change of the solvation/desolvation properties within the ligand series. The study shows that it is possible to modulate the strength of a halogen bond in a protein-ligand complex as was designed based on the previous studies of low-molecular-weight complexes.

Polyhedral metallacarboranes are used mainly as ion-pairing agents and recently have been recognized as potent inhibitors of HIV protease. They are characterized by exceptional hydrophobicity, rigid geometry, delocalized negative charge, ion-pairing behavior, and strong acidity of their conjugated acids. The completely novel phenomenon, association of these promising pharmaceutical tectons in aqueous solutions, is described here. The behavior of two structural types of metallacarboranes, [bis(1,2-dicarbollide)cobaltate(1-)] and bis[(3)-1,2-dicarbollylcobalt]-(3,6)-1,2-dicarbacanastide(2-)], in aqueous solution was studied by a combination of static and dynamic light scattering and microscopy methods. Spherical aggregates with radii of ca. 100 nm and fairly monodisperse nanostructures were found in aqueous solutions. The behavior of nanoaggregates is fairly complex and depends on the concentration and aging of the solutions. The particles are stabilized in the solution by counterions. The formation of larger clusters upon dilution of bis(1,2-dicarbollide)cobaltate(1-) solutions was observed. The secondary aggregation can be suppressed by addition of NaCl. Gel permeation chromatography measurements of sodium bis(1,2-dicarbollide)cobaltate(1-) show that the majority of matallacarborane molecules form nanoaggregates and only a small amount of the metallacarborane remains molecularly soluble or forms small oligomers.

We prepared two fluorescein-[3-cobalt(III) bis(1,2-dicarbollide)](-) conjugates. They are sparingly soluble in water and form large aggregates in aqueous solutions. An extensive study on their spectral and aggregation behavior was carried out. To prepare their well-defined dispersion in aqueous systems, we studied the interaction of both probes with two biocompatible amphiphilic systems, cyclodextrins, which are frequently used in drug-delivery systems, and phospholipid membranes, which are the major constituents of cell barriers in living organisms. The presence of fluorescein in both conjugates allows us to study their behavior in detail by steady-state and time-resolved fluorometry, fluorescence correlation spectroscopy, and fluorescence lifetime imaging. The self-assembly of these metallacarboranes in aqueous solutions was studied by dynamic light scattering. The study shows that the compounds interact with cyclodextrins that increases their solubility in water, and they solubilize easily in phospholipid bilayers.

The anion [3,3'-Co(C2B9H11)2](-) ([COSAN](-)) produces aggregates in water. These aggregates are interpreted to be the result of C-H⋅⋅⋅H-B interactions. It is possible to generate aggregates even after the incorporation of additional functional groups into the [COSAN](-) units. The approach is to join two [COSAN](-) anions by a linker that can adapt itself to act as a crown ether. The linker has been chosen to have six oxygen atoms, which is the ideal number for K(+) selectivity in crown ethers. The linker binds the alkaline metal ions with different affinities; thus showing a distinct degree of selectivity. The highest affinity is shown towards K(+) from a mixture containing Li(+), Na(+), K(+), Rb(+) and Cs(+); this can be indicative of pseudo-crown ether performance of the dumbbell. One interesting possibility is that the [COSAN](-) anions at the two ends of the linker can act as a hook-and-loop fastener to close the ring. This facet is intriguing and deserves further consideration for possible applications. The distinct affinity towards alkaline metal ions is corroborated by solubility studies and isothermal calorimetry thermograms. Furthermore, cryoTEM micrographs, along with light scattering results, reveal the existence of small self-assemblies and compact nanostructures ranging from spheres to single-/multi-layer vesicles in aqueous solutions. The studies reported herein show that these dumbbells can have different appearances, either as molecules or aggregates, in water or lipophilic phases; this offers a distinct model as drug carriers.

Solids that combine long-range order with rapid molecular reorientation offer a promising approach for the development of a novel class of functional materials with potential applications in materials science and nanotechnology. In this contribution, the capability of dicarbollide ions to undergo self-assembly processes with suitable macromolecules is demonstrated, and a strategy leading to the formation of structurally and dynamically well-defined amphidynamic polymeric composites is introduced. For this purpose, three amphidynamic nanocomposites were synthesized via the selfassembly of cobalt bis(dicarbollide) anions (CoD − ), with neutral poly(ethylene oxide) (PEO), and two isomers of poly(vinylpyridine), P2VP and P4VP, in protonated form. All of the systems were characterized by a combined study employing WAXS, advanced solid-state NMR, and quantum chemical calculations. It was found out that the interaction of neutral PEO with CoD − ions driven by weak dihydrogen bonding resulted in the formation of a uniquely organized periodic structure. In contrast, the self-assembly of the systems based on the electrostatic interactions (charge-transfer-assisted hydrogen bonding) of P2(4)VP was controlled by the position of the positive charge in pyridine ring and resulted in unique well-defined orientations of the CoD − ions (parallel and perpendicular) with respect to the polymer chains. In addition, the CoD − ions exhibited uniaxial relatively large-amplitude rotational motions in all of the nanocomposites over the broad range of T g . The motional amplitudes executed by the CoD − ions are significantly more extensive than those of the polymer segments in all of the systems. Macromolecules thus represent a rigid support (stator) for the more mobile CoD − ions (rotators). The obtained findings revealed that a relatively simple self-assembly procedure could be used for the preparation of well-defined amphidynamic nanocomposites, thereby opening a route to construct sophisticated supramolecular systems.

Aqueous solutions of self-assembled nanoparticles formed by biocompatible diblock copolymers of poly(epsilon-caprolactone)-block-poly(ethylene oxide) (PCL-PEO) with the same molar mass of the PEO block (5000 g mol-1) and three different molar masses of the PCL block (5000, 13 000, and 32 000 g mol-1) have been prepared by a fast mixing the copolymer solution in a mild selective solvent, tetrahydrofuran (THF)/water, with an excess of water, that is, by quenching the reversible micellization equilibrium, and a subsequent removal of THF by dialysis of the water-rich solution against water. The prepared nanoparticles have been characterized by static and dynamic light scattering and atomic force microscopy imaging. It was found that stable monodisperse nanoparticles are formed only if the initial mixed solvent contained 90 vol % THF. The results show that the prepared nanoparticles are spherical vesicles with relatively thick hydrophobic walls, that is, spherical core/shell nanoparticles with the hollow core filled with the solvent.

The micellization behavior of a hydrophobically modified double tagged polystyrene-blockpoly(methacrylic acid) diblock copolymer, PS-N-PMA-A was studied in 1,4-dioxane-H2O mixtures by light-scattering and fluorescence techniques. This polymer was fluorescently tagged by a naphthalene moiety at the junction of the blocks and by anthracene at the end of the PMA block. The behavior of a single-tagged sample, PS-N-PMA, and low-molar-mass analogues were studied for comparison. Multimolecular polymeric micelles with compact PS cores and PMA shells may be prepared indirectly by dialysis from 1,4-dioxane-rich mixtures as water is a strong selective precipitant for the PS block. In both types of micelles, the naphthalene tags are trapped in a nonpolar and fairly viscous core/shell interfacial region. The hydrophobic anthracene tags in PS-N-PMA-A are at the ends of the water-soluble PMA blocks and tend to avoid the bulk polar solvent, burying themselves into the shell. The collapse of a fraction of the PMA chains is an enthalpy-driven process, but it is entropically unfavorable, and the distribution of the anthracene tags in the shell is a result of the enthalpy-to-entropy interplay. Measurements of direct nonradiative excitation energy transfer (NRET) were performed on PS-N-PMA-A to estimate the distribution of the anthracene-tagged PMA ends in the shell. The experimental fluorometric data show that the anthracene tags penetrate deeply into the shell in water-rich solvents, although there is considerable fluctuation in the distance of closest approach to the excited naphthalene. We find that the collapsed PMA chains and loops in the shell results in the counterintuitive effect that the hydrodynamic radius is significantly increased compared to the corresponding unmodified PS-N-PMA.