1D Supramolecular Assemblies That Crystallize and Form Gels in Response to the Shape-Complementarity of Alcohols.

N-9-Fluorenylmethyloxycarbonyl (Fmoc)- and C-tertiary butyl (t-Bu)-protected glutamate (L-2), bearing a phenanthroline moiety at the side residue, forms 1D supramolecular assemblies via H-bonding as well as undergoing π-stacking interactions to afford crystals or gels that depend on the shape-complementarity of coexisting alcohols, as demonstrated by structural analyses on these assemblies by means of single-crystal X-ray diffractometry and supplemented with small- and wide-angle X-ray scattering data. Moreover, the rheological measurements on the gels help to define a model for when gels and crystals are expected and found. These observations and conclusions highlight an important, but not very appreciated, aspect of solute-solvent interactions within supramolecular assemblies that can allow the constituent-aggregating molecules in some systems to exhibit high selectivity toward the structures of their solvents. The consequences of this selectivity, as demonstrated here by single-crystal and powder X-ray diffraction data, can lead to self-assembled structures which alter completely the bulk phase properties and morphology of the materials. In that regard, rheological measurements have helped to develop a model to explain when gels and phase-separated mixtures of crystals and solvents are expected.

Dollars and Sense: The Business of Pediatric Surgery.

INTRODUCTION: This study evaluated North American pediatric surgeons' opinions and knowledge of business and economics in medicine and their perceptions of trends in their healthcare delivery environment. METHODS: We conducted an elective online survey of 1119 American Pediatric Surgical Association members. Over 8 mo, we iteratively developed the survey focused on four areas: opinion, knowledge, current practice environment, and trends in practice environment over the past 5 y. RESULTS: We received 227 (20.3%) complete surveys from pediatric surgeons. One hundred ninety four (85.5%) perceive healthcare as a business and most (85.9%) believe healthcare decisions may affect patients' out-of-pocket expenses. More than half (51.1%) of surgeons believe it has become more challenging to perform emergent cases and most believe staff quality has decreased for elective (56.4%) and emergent (63.0%) cases over the past 5 y. CONCLUSIONS: Pediatric surgeons recognize that medicine is a business and have concerns regarding the decreasing quality of operating room staff and the increasing difficulty providing surgical care over the last 5 y.

Effects of cyclic and acyclic amidine side-chains on the properties of polysiloxane ionomers constructed in situ from three uncharged components.

Ionomers, polysiloxanes with imidazolinium dithiocarbamate side chains, have been synthesized in situ from three uncharged components-a polysiloxane with imidazole side chains, CS2, and hexylamine or octadecylamine. Their structural and dynamic properties are compared over a temperature range of 0-50 °C with those of the analogous ionomers in which the polysiloxanes have amidinium side chains. The results, primarily from differential scanning calorimetry, powder X-ray diffraction measurements, and rheology show that the small structural (and smaller electronic) differences between the cyclic 5-membered ring imidazolinium and acyclic amidinium groups have marked effects on the bulk properties of the ionomers. These include their shear strengths and the manner in which the microcrystalline portions of the ionomers with dithiooctadecylcarbamate anions are packed. Thus, it is possible to finely tune the natures of the ionomers from one polysiloxane by changing temperature, the chain length of the alkylamine, and the nature of the base attached to the polysiloxane chain. Why these changes occur to the various properties is discussed.

NMR spectral fingerprint patterns as diagnostics for the unambiguous configurational analysis of the classic organo-gelator 1,3:2,4-dibenzylidene-d-sorbitol (DBS) and its derivatives.

On the basis of experimental data and density functional theory (DFT) chemical shift and scalar coupling predictions, simple spectral nuclear magnetic resonance (NMR) fingerprint patterns have been established for the determination of the configuration in 1,3:2,4-dibenzylidene-d-sorbitol (DBS), a classic low molecular weight gelator, and its derivatives. The results rigorously prove the orientation of the phenyl rings in DBS that had been previously assumed in the literature on the basis of thermodynamic arguments.

Thiol- and Disulfide-Based Stimulus-Responsive Soft Materials and Self-Assembling Systems.

Properties and applications of synthetic thiol- and disulfide-based materials, principally polymers, are reviewed. Emphasis is placed on soft and self-assembling materials in which interconversion of the thiol and disulfide groups initiates stimulus-responses and/or self-healing for biomedical and non-biomedical applications.

Benzil Photoperoxidations in Polymer Films and Crosslinking by the Resultant Benzoyl Peroxides in Polystyrene and Other Polymers.

Benzil (BZ) can be converted almost quantitatively to benzoyl peroxide (BP) in aerated polymer films upon irradiation at >400 nm (i.e., the long-wavelength edge of the n→π* absorption band of BZ, where BP does not absorb). Here, we summarize results for the photoperoxidation of BZ structures with molecular oxygen, principally in glassy polymer matrices. Some of the polymers are doped directly with BZ or its derivatives, and others, contain covalently attached BZ pendant groups from which BP groups are derived. While the decomposition of low-molecular-weight BP doped into polymer films (such as those of polystyrene (PS)) results in a net decrease in polymer molecular weight, thermal decomposition of pendant BP groups is an efficient method for chain crosslinking. Crosslinking of PS films doped with a molecule containing two covalently linked BZ or BP groups proceeds in a similar fashion. Free radicals from the covalently attached BP allow grafting of new monomers, as well. Additionally, the use of radiation filtered through masks has been used to create patterns of polymers on solid surfaces. Crosslinking of photodegradable poly(phenyl vinyl ketone) with BP structures obtained by photoperoxidation of BZ structures for the preparation of photodegradable polymer networks is described as well. In sum, the use of BZ and BP and their derivatives offers simple and convenient routes for modifying polymer chains and, especially, for crosslinking them. Specific applications of each use and process are provided. Although applications with PS are featured here, the methodologies described are amenable to a wide variety of other polymers.

Experimental and Theoretical Investigation of Excited-State Intramolecular Proton Transfer Processes of Benzothiazole Derivatives in Amino-polydimethylsiloxanes before and after Cross-Linking by CO2.

The changes in the ability of three fluorescent derivatives of 2-(2'-hydroxyphenyl)benzothiazole to undergo excited-state intramolecular proton transfer (ESIPT) processes have been correlated with the rheological properties of four amino-polydimethylsiloxanes with different molar masses and containing different amounts of monomer units with amino pendant groups, in the presence and absence of a cross-linking molecule, CO2. The changes lead to a variety of species (keto, enol, and enolate forms) in both the ground and excited states. Calculations using the density-functional theory/time-dependent density-functional theory method at the CAM-B3LYP/6-311++G(d,p) level helped to identify how ESIPT is involved in the formation of the intermediates. The results demonstrate that proton transfer in 2-(2'-hydroxyphenyl)benzothiazoles is a powerful tool to identify local changes in the viscosity and micropolarity of the environment that are attributed to the structural differences of the amino-polydimethylsiloxanes and their cross-linking.

Multiple-State Emissions from Neat, Single-Component Molecular Solids: Suppression of Kasha's Rule.

Three rigid and structurally simple heterocyclic stilbene derivatives, (E)-3H,3'H-[1,1'-biisobenzofuranylidene]-3,3'-dione, (E)-3-(3-oxobenzo[c] thiophen-1(3H)-ylidene)isobenzofuran-1(3H)-one, and (E)-3H,3'H-[1,1'-bibenzo[c] thiophenylidene]-3,3'-dione, are found to fluoresce in their neat solid phases, from upper (S2 ) and lowest (S1 ) singlet excited states, even at room temperature in air. Photophysical studies, single-crystal structures, and theoretical calculations indicate that large energy gaps between S2 and S1 states (T2 and T1 states) as well as an abundance of intra and intermolecular hydrogen bonds suppress internal conversions of the upper excited states in the solids and make possible the fluorescence from S2 excited states (phosphorescence from T2 excited states). These results, including unprecedented fluorescence quantum yields (2.3-9.6 %) from the S2 states in the neat solids, establish a unique molecular skeleton for achieving multi-colored emissions from upper excited states by "suppressing" Kasha's rule.

Poly(vinyl alcohol)-induced thixotropy of an l-carnosine-based cytocompatible, tripeptidic hydrogel.

The generally poor mechanical stability of hydrogels limits their use as functional materials for many biomedical applications. In this work, a poly(vinyl alcohol) (PVA) embedded hybrid hydrogel of a ß-amino acid-containing Fmoc-protected tripeptide was produced at physiological pH (7.4) and room temperature. The hydrogel system was characterized by a number of techniques, including UV-vis, fluorescence, circular dichroism, FT-IR spectroscopy, electron microscopy, and rheology. While the tripeptide-based pure hydrogel was found to be unstable after ca. half an hour, addition of PVA, a water soluble polymer, increased the temporal and mechanical stability of the hydrogel. A rheological step-strain experiment demonstrates that the peptide-polymer hydrogel is thixotropic. Results from a fluorescence probe study and transmission electron microscopy reveal that addition of PVA increases both the fibre diameter and entanglement. Circular dichroism spectra of the hydrogels confirm the formation of aggregates with supramolecular chirality. The thixotropic nature of the hydrogel has been exploited to entrap and release doxorubicin, an anticancer drug, under physiological conditions. Furthermore, an MTT assay of the Fmoc-tripeptide using AH927 cells confirmed its cytocompatibility, which broadens the utility of the hybrid gel for biomedical applications.

l-Carnosine-Derived Fmoc-Tripeptides Forming pH-Sensitive and Proteolytically Stable Supramolecular Hydrogels.

A series of ß-amino acid containing tripeptides has been designed and synthesized in order to develop oligopeptide-based, thermoreversible, pH-sensitive, and proteolytically stable hydrogels. The Fmoc [N-(fluorenyl-9-methoxycarbonyl)]-protected tripeptides were found to produce hydrogels in both pH 7 and 2 buffers at a very low concentration (<0.2% w/v). It has been shown that the Fmoc group plays an important role in the gelation process. Also a dependence of gelation ability on hydrophobicity of the side chain of the Fmoc-protected α-amino acid was observed. The effect of the addition of inorganic salts on the gelation process was investigated as well. Spectroscopic studies indicated formation of J-aggregates through π-π stacking interactions between Fmoc groups in solution as well as in the gel state. In the gel phase, these self-assembling tripeptides form long interconnected nanofibrils leading to the formation of 3-dimensional network structure. The hydrogels were characterized by various techniques, including field emission electron microscopy, transmission electron microscopy, atomic force microscopy, rheology, Fourier transform IR, circular dichroism (CD), and wide-angle X-ray diffraction (WAXD) spectroscopy. The CD studies and WAXD analyses show an antiparallel ß-sheet structure in the gel state. l-Phenylalanine and l-tyrosine containing tripeptides formed helical aggregates with handedness opposite to those containing l-valine and l-leucine residues. The mechanical stability of the hydrogels was found to depend on the hydrophobicity of the side chain of the tripeptide as well as on the pH of the solution. Also, the tripeptides exhibit in vitro proteolytic stability against proteinase K enzyme.

Molecular Nuances Governing the Self-Assembly of 1,3:2,4-Dibenzylidene-d-sorbitol.

1,3:2,4-Dibenzylidene-d-sorbitol (DBS) is the gold-standard for low-molecular-weight organogelators (LMOGs). DBS gels a wide array of solvents, as illustrated by the large Hansen sphere representing gels (2δd = 33.5 MPa1/2, δp = 7.5 MPa1/2, and δh = 8.7 MPa1/2; radius = 11.2 MPa1/2). Derivatives of DBS have been synthesized to isolate and determine molecular features essential for organogelation. In this work, π-π stacking and hydrogen bonding are the major noncovalent interactions examined. The importance of π-π stacking was studied using 1,3:2,4 dicyclohexanecarboxylidene-d-sorbitol (DCHS), which eliminates possible π-π stacking while still conserving the other structural aspects of DBS. The replacement of the benzyl groups with cyclohexyl groups led to a very a poor gelator; only one of the several solvents examined, carbon tetrachloride, formed a gel. 1,3:2,4-Diethylidene-d-sorbitol (DES), another DBS analogue incapable of π-π stacking but with very different polarity, gelated a large Hansen space (2δd = 34.0 MPa1/2, δp = 10.9 MPa1/2, and δh = 10.8 MPa1/2; radius = 9.2 MPa1/2). DES gels solvents with higher δp and δh values than DBS. To assess the role of hydrogen bonding, DBS was acetalated (A-DBS), and it was found that the Hansen space gelated by A-DBS shifted to less polar solvents with higher hydrogen-bonding Hansen solubility parameters (HSPs) (2δd = 33.8 MPa1/2, δp = 6.3 MPa1/2, and δh = 9.6 MPa1/2; radius = 11.1 MPa1/2) than for DBS. These systematic structural modifications are the first step in exploring how specific intermolecular features alter aspects of Hansen space corresponding to positive gelation outcomes.

Photophysics of N,N-dimethyl-3-(1-indolyl)propan-1-ammonium chloride and related derivatives.

The photophysical properties of two new indole derivatives have been examined by steady-state and dynamic spectroscopic methods. The ground-state structures and conformations of 3-(1-indolyl)-N,N-dimethylpropan-1-ammonium chloride (InCl) and 3-(1-indolyl)-N,N,N-trimethylpropan-1-ammonium chloride (MeInCl) have been examined through density functional theory calculations. These calculations reveal a preference for a 'closed' conformation which places the cationic ammonium group in proximity to the π-electron cloud in low polarity environments. This interaction is best described as an intramolecular hydrogen-π bond in the case of InCl and a cation-π interaction for MeInCl. The ground-state conformational equilibria are influenced by changes in the dielectric constant of the solvent, resulting in a variety of photophysical behaviors. The excitation/emission spectra, fluorescence quantum yields, and excited-state lifetimes, are reported for InCl, MeInCl, and a reference compound, 1-methylindole, in 1,4-dioxane (ε = 2), acetonitrile (ε = 37), and water (ε = 78) where solubility allows. Data from these solvents provide evidence for independent fluorescence quenching pathways for InCl and MeInCl. In addition, they lead to insights into the complexities of indole photophysics by demonstrating the sensitivity of the locally-excited states to changes in charge-density and solvent environment.

Proton-coupled charge-transfer reactions and photoacidity of N,N-dimethyl-3-arylpropan-1-ammonium chloride salts.

Photoinduced intermolecular proton-transfer processes from N,N-dimethyl-3-arylpropan-1-ammonium chloride salts (ArCl, with aryl as 1-pyrenyl, 9-anthryl, and 2-naphtyl) to a solvent molecule have been investigated by steady-state and dynamic spectroscopic methods. The intermolecular proton-transfers are coupled either to the formation of an exciplex or to a solvent-separated ion pair in what we have termed a 'proton-coupled charge-transfer reaction'. A range of solvents has been observed to mediate both the ground-state conformations of the ArCl and the extent of electron transfer. Unlike typical photoacids, in which through-bond interactions control photoacidity, through-space charge-transfer interactions are responsible in the excited singlet states of the ArCl. Transient absorption experiments reveal a range of electronic comportments in the excited-states of the ArCl. Excited-state pKa values of -3.4, 1.3, and -3.3 in THF were calculated using a Förster-like approach for the 1-pyrenyl, 9-anthryl, and 2-naphthyl salts, respectively. The observed rate of proton-transfer was found to be independent of the thermodynamic driving force and the short-term reversibility of these reactions has been approximated. The data suggest how other systems may be designed to facilitate this novel process.

New Insights into an Old Problem. Fluorescence Quenching of Sterically-Graded Pyrenes by Tertiary Aliphatic Amines.

Although the quenching of singlet-excited states of aromatic molecules by amines has been studied for several decades, important aspects of the mechanism(s) remain nebulous. To address some of the unknowns, steric, and electronic factors associated with the quenching of the singlet-excited states of three electronically related aromatic molecules, pyrene, 1,3,6,8-tetraphenylpyrene (TPPy), and 1,3,6,8-tetrakis(4-methoxy-2,6-dimethylphenyl)pyrene (PyOMe), by a wide range of tertiary aliphatic amines have been assessed quantitatively. Correlations among the steric and electronic properties of the amines and the pyrenes (e.g., sizes, shapes, conformational labilities, excitation energies, and oxidation or reduction potentials) have been used in conjunction with the steady-state and dynamic fluorescence quenching data and DFT calculations on the ground and excited state complexes to make quantitative assessments of the steric and electronic factors controlling the quenching processes. PyOMe is a rather rigid bowl-like molecule that, in its electronic ground state, does not make stable complexes with amines in solution. TPPy has a shallower bowl-like shape that is much more flexible. Experiments conducted with a crystalline ground-state complex of an amine and PyOMe demonstrate (as assumed in many other studies but not shown conclusively heretofore) that the geometry needed for quenching the excited singlet state of PyOMe must place the lone-pair of electrons of the amines over the π-system of the pyrenyl group. Furthermore, there is a significant dependence on the shape and size of the amine on its ability to quench PyOMe, but not on the less conformationally constrained TPPy. The conclusions obtained from these studies are clearly applicable to a wide variety of other systems in which fluorescence from an aromatic moiety is being quenched, and they provide insights into how weak host-guest pairs interact.

Influence of Cations on the Fluorescence Quenching of an Ionic, Sterically Congested Pyrenyl Moiety by Iodide in Water.

Quenching of the excited singlet states of a water-soluble, sterically congested tetraarylpyrene, 1,3,6,8-tetrakis(2,6-dimethyl-4-(α-carboxy)methoxyphenyl)pyrene (Py4C), by a series of iodide salts has been investigated by steady-state and time-resolved fluorescence measurements. Access to the pyrenyl group of Py4C is restricted sterically as a result of the four flanking (2,6-dimethylphenoxy)acetic acid groups and the energy costs associated with their rotation. Deprotonation of the carboxylic acid groups of Py4C permits examination of ion-ion electrostatic interactions on the rates of quenching by iodide salts in which different steric and electrostatic factors are introduced by varying the cationic portions. At the same concentrations and with the same cations, chloride anions are ineffective quenchers. The quenching rate constants of Py4C by iodide are found to correlate linearly with the ionic radii of the cations and their enthalpies of hydration. These correlations are discussed in terms of the Hofmeister series. Furthermore, the results indicate that the cations that flank Py4C decrease the quenching efficiency of iodide through polarization and shielding effects (i.e., lowering the effective charge), which isolate to varying degrees the π-system. The effects of the different cations on quenching the fluorescence of a simpler and sterically unencumbered pyrenyl derivative, 1-pyrenylbutyric acid (PyBu), by iodide are much smaller. Overall, the results with Py4C indicate that the fluorescence quenching efficiency by iodide is influenced by direct interactions with the cations associated with the carboxylate groups of Py4C and not the solvation of water molecules. This observation is germane to a topic of current debate: Are the effects of the cations more closely related to bulk water properties or to direct ion-ion interactions? The conclusions obtained from these studies are applicable clearly to a wide variety of other systems in which ion pairing influences cooperative or inhibitory interactions.

Mechano-Responsive, Thermo-Reversible, Luminescent Organogels Derived from a Long-Chained, Naturally Occurring Fatty Acid.

The gelating ability of an α-diketo derivative of oleic acid, 9,10-dioxooctadecanoic acid (DODA), is investigated. DODA can gelate aromatic liquids and many other organic liquids. By contrast, none of the liquids examined can be gelated by the methyl ester of DODA. DODA is a more efficient gelator than stearic acid and the monoketo derivative due to its more extensive intermolecular dipole-dipole interactions. Formation of organogels of DODA can be induced by both thermal and mechanical stimuli, during which the luminescent and mechanical properties can be modulated significantly. The emission from DODA in 1-octanol exhibits a large, reversible, hypsochromic shift (≈25 nm) between its thermally cycled gel and sol states. The emission changes have been exploited to probe the kinetics of the aggregation and deaggregation processes. DODA is the simplest gelator of which we are aware that exhibits a reversible shift in the emission. Although the self-assembled fibrillar networks of the DODA gels in 1-octanol, benzonitrile, or silicone oil are crystalline, isothermal mechanical cycling between the gel and the sol states is rapid and can be repeated several times (i.e., they are thixotropic). The single-crystal structure of DODA indicates that extended intermolecular dipole-dipole interactions are crucial to the thermal and mechanical formation of DODA gels and the consequential changes in emissive and mechanical properties. From analyses of structural information, gelator packing, and morphology differences, we hypothesize that the mechanical destruction and reformation of the gel networks involves interconversion between the 3D networks and 1D fiber bundles. The thermal processes allow the fibrillar 3D networks and their 0D components (i.e., isolated molecules or small aggregates of DODA) to be interconverted. These results describe a facile approach to the design of mechano-responsive, thermo-reversible gels with control over their emission wavelengths.

Insights into the Formation and Structures of Molecular Gels by Diimidazolium Salt Gelators in Ionic Liquids or "Normal" Solvents.

Insights are provided into the properties of molecular gels formed by diimidazolium salts both in "normal" solvents and ionic liquids. These materials can be interesting for applications in green and sustainable chemistry in which ionic liquids play a significant role, like catalysis and energy. In particular, two positional isomers of a diimidazolium cation have been examined with a wide range of anions for their ability to form gel phases. In particular, di-, tri-, and tetravalent anions bearing aliphatic or aromatic spacers were paired with the divalent cations. The properties of the organo- and ionogels formed have been analyzed by means of several different techniques, including calorimetry, rheology, resonance light scattering, UV/Vis absorption, polarizing optical microscopy, and powder X-ray diffraction measurements. The investigations performed enabled us to obtain a wide range of conductive materials characterized by a high thermal stability and a low corrosiveness of the gelator (organogels) or of both gelator and solvent (ionogels). The information gained should be useful in the broader quest to identify and promote their applications.

Insights into the Gelating Abilities of Ricinelaidic Acid and its Ammonium Salts: How do Stereochemistry, Charge, and Chain Lengths Control Gelation of a Long-Chain Alkenoic Acid?

The gelating abilities of ricinelaidic acid (d-REA), the trans-isomer of ricinoleic acid (d-RA), and a series of its alkylammonium and alkane-α,ω-diammonium salts have been examined in a wide range of organic liquids. The gelation efficiency of the trans acid is much better than that of the cis, although neither is as efficient as is the completely saturated molecular gelator analogue, (R)-12-hydroxystearic acid (d-12HSA). The formation of ammonium salts also improves the gelation ability of d-REA in high polarity liquids. The gelating properties are highly dependent upon the chain length of the alkyl group of the alkylammonium salts, but not very dependent on the chain length of the alkane-α,ω-diammonium salts. Structural insights from Fourier transform infrared spectroscopy and powder X-ray diffraction indicate that the absence or presence of unsaturation, the incorporation of (charged) ammonium centers, and the different chain lengths of the alkylammonium salts lead to different packing arrangements and different strengths of H-bonding interactions within the gel assemblies of the d-REA derivatives. Insights into the relationships among the various systematic structural changes to d-REA and the properties of their aggregated structures, including the gel states, are provided.

Colloidal Properties of Aqueous Poly(vinyl acetate)-Borate Dispersions with Short-Chain Glycol Ethers.

We report the influence of adding five short-chain glycol ethers (SCGEs) on the structure, stability, and viscoelastic properties of aqueous dispersions of partially hydrolyzed poly(vinyl acetate) and borax. The properties of these gel-like materials have been investigated as a function of the structure of the added SCGE both below and above the critical aggregation (or micellar) concentrations using (11) B and (13) C NMR, rheology, and small-angle neutron scattering. The results indicate that the SCGE aggregation behavior is not affected by incorporation into the gel-like network. However, changes in the viscoelasticity and structural properties of the dispersions were detected that can be correlated to the nature of the solvent system. Also, the ability of these materials to clean an unvarnished acrylic paint surface coated with synthetic soil has been evaluated using colorimetery, and the surface of the dispersion after cleaning was visualized with scanning electron microscopy.

Correlations between thixotropic and structural properties of molecular gels with crystalline networks.

This review focuses on correlations between the thixotropic and structural properties of molecular gels having crystalline fibrillar networks (SAFINs). Formation of thixotropic molecular gels and their recovery after the application of destructive strain depends on the strength and type of intermolecular interactions in the SAFINs of the gelator molecules. Here, we limit our discussion to gelator molecules with simple structures in order to dissect more easily the important contributors to the thixotropic behaviors. Possible mechanisms to explain the thixotropic phenomena, involving the transformation of the SAFINs into unattached objects, and their reassembly into 3-dimensional networks, are advanced. The data are analyzed to provide insights into the rational design of thixotropic molecular gelators.