Manipulating Assemblies in Metallosupramolecular Gels, Driven by Isomeric Ligands, Metal Coordination, and Adaptive Binary Gelator Systems.

Metallosupramolecular gel (MSG) is a unique combination of metal-ligand coordination chemistry and supramolecular gel chemistry with extraordinary adaptivity and softness. Such materials find broad uses in industry, pharmaceutical and biomedical sectors, and in technology generation among many others. Pyridyl-appended bis(urea) gelator systems have been extensively studied as potential MSG-forming materials in the presence of various metal ions. The previous molecular engineering approaches depicted competitive intermolecular and intramolecular binding modes involving urea and pyridyl groups and further fine-tuned by the presence of various molecular spacers. In those studies, formation of intermolecular hydrogen bonding among urea moieties to form urea tape was found to be the key factor in one-dimensional assembly and gel formation. In the present study, we show how two isomeric pyridyl-appended bis(urea) ligands can be designed appropriately to essentially eliminate the interference of competitive factors, leaving the intermolecular urea assembly practically unaffected even in the presence of metal ions. We found that one of the two ligands (L2) and the mixed ligand (L1 + L2) assemblies formed gel in the presence and absence of various metal ions. A metal ion with a linear coordination geometry significantly strengthened the gels. Moreover, an inherently weak L1 + L2 assembly appears to be more adaptive in accommodating larger metal ions especially with nonlinear coordination geometry preferences. Small-angle neutron scattering and rheological, spectroscopic, and morphological characterizations, collectively, capture a detailed interplay among ligand assembly, metal-ligand coordination, and adaptivity, driven by the pure versus mixed ligand assemblies. The knowledge gathered from the present study would be highly beneficial in engineering the metallosupramolecular polymeric assemblies toward their functional applications.

Structural insights into self-assembly of a slow-evolving and mechanically robust supramolecular gel via time-resolved small-angle neutron scattering.

The supramolecular assembly process is a widespread phenomenon found in both synthetically engineered and naturally occurring systems, such as colloids, liquid crystals and micelles. However, a basic understanding of the evolution of self-assembly processes over time remains elusive, primarily owing to the fast kinetics involved in these processes and the complex nature of the various non-covalent interactions operating simultaneously. With the help of a slow-evolving supramolecular gel derived from a urea-based gelator, we aim to capture the different stages of the self-assembly process commencing from nucleation. In particular, we are able to study the self-assembly in real time using time-resolved small-angle neutron scattering (SANS) at length scales ranging from approximately 30 Å to 250 Å. Systems with and without sonication are compared simultaneously, to follow the different kinetic paths involved in these two cases. Time-dependent NMR, morphological and rheological studies act complementarily to the SANS data at sub-micron and bulk length scales. A hollow columnar formation comprising of gelator monomers arranged radially along the long axis of the fiber and solvent in the core is detected at the very early stage of the self-assembly process. While sonication promotes uniform growth of fibers and fiber entanglement, the absence of such a stimulus helps extensive bundle formation at a later stage and at the microscopic domain, making the gel system mechanically robust. The results of the present work provide a thorough understanding of the self-assembly process and reveal a path for fine-tuning such growth processes for applications such as the cosmetics industry, 3D printing ink development and paint industry.

Assessment of the in vitro toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application.

Calixarenes are known to form host-guest complexes and supramolecular nanoassemblies with well-defined architectures. However, the use of these materials in conjunction with drug moieties is still under explored. One reason is the insuffcient biocompatibility studies. Our present study represents a systematic in vitro investigation of the cytotoxicity associated with C-methylresorcin[4]arene, C-methylpyrogallol[4]arene, p-phosphonated calix[8]arene and a metal-seamed calixarene-copper(II) complex, using human HEK293 and rat C6G cell lines and two different cell viability assays (MTT and CellTiter-Glo) to avoid species-biased results. All compounds showed low to moderate toxicity. The trend in the CC50 values indicated that the suppression of the coordination ability and the presence of phosphonate groups decrease the overall cytotoxicity of the compounds. The results of this study not only establish calixarenes and their immediate families as potential drug carriers and drug modifiers, but also reveal a pathway for fine-tuning their toxicological behaviour by appropriate chemical modification.

Supramolecular Gel as the Template for Catalysis, Inorganic Superstructure, and Pharmaceutical Crystallization.

A supramolecular gel is a fascinating combination of flexibility and orderliness. While the supramolecular nature of crosslinking contributes towards the adaptivity and the reversibility of the system, orderliness at the molecular level amplifies the functional output and induces extraordinary selectivity into the system. Therefore, use of supramolecular gels as the soft template is an emerging area of research, which includes but not limited to catalysis of a chemical or a photochemical process, transcription of gel property to a substrate, or even controlling the nucleation of drug molecules. This review aims to highlight the template effect of supramolecular gels in the above-mentioned areas relevant to novel fundamental chemistry, technology, and healthcare.

Low Molecular Weight Supramolecular Gels Under Shear: Rheology as the Tool for Elucidating Structure-Function Correlation.

Self-healing low molecular weight supramolecular gels (SMGs) represent an emerging class of smart materials, which can closely mimic the complex biological healing process, such as blood clotting, bone repair or wound healing. However, a lack of understanding of the structure-function correlation in the self-assembly process limits their molecular design and subsequent property tuning. The indispensability of a rheological study on supramolecular gels lies in direct transcription of the assembly property to the viscoelastic behavior of the material. This is similarly relevant to healable and non-healable systems. Thus, using rheology as a tool for elucidating structure-function relationships in self-assembled systems has huge potential. This review article will depict a general introduction of rheology in the field of soft matter including SMGs, followed by representative studies with interpretations, and discussion on future challenges. Altogether, this would be an effort, where an in-depth rheological study complemented with a real-time visualization with the help of microscopy, and introduction of other sophisticated real-time experiments, could be a step forward to capture the mystery of self-assembly process.

Investigating the effect of supramolecular gel phase crystallization on gel nucleation.

Supramolecular gel phase crystallization offers a new strategy for drug polymorph screening and discovery. In this method, the crystallization outcome depends on the interaction between solute and gel fibre. While supramolecular gels have shown success in producing new polymorphs and crystals with novel morphologies, role of the gel and nature of gel-solute interaction remains largely unexplored. The present study aims to provide a comprehensive picture of the structural evolution of a supramolecular gel produced from a bis(urea) based gelator (G) in the presence of a polymorphic drug carbamazepine (CBZ). The structural aspects of the gel have been assessed by single crystal X-ray analysis, X-ray powder diffraction (XRPD) and solid state NMR spectroscopy. Small Angle Neutron Scattering (SANS) has been used to follow the changes in gel structure in the presence of CBZ. Visual evidence from morphological study and structural evolution observed at a macroscopic level from rheological measurements, shows good agreement with the SANS results. The concentration of the gelator and the relative proportion of G to CBZ were found to be crucial factors in determining the competitive nucleation events involving gelation and crystallization. At a critical G to CBZ ratio the effect of CBZ on gel structure was maximum and fiber bundling in the gel was found to be critically affected. This study offers important information about how the interplay of gelator assembly and gel-solute interactions can fine-tune the nucleation events in a supramolecular gel phase crystallization.

Multifaceted Supramolecular Interactions from C-Methylresorcin[4]arene Lead to an Enhancement in In Vitro Antibacterial Activity of Gatifloxacin.

Mimicking the antibacterial activity of polyphenols in synthetic systems is an attractive approach for the development of new active pharmaceutical ingredients. Resorcinarenes represent a class of polyphenols, which have been exploited for decades for their attractive chemical scaffold suitable for forming host-guest complexes with hydrophobic guest molecules. However, the polyphenolic character of resorcinarenes, which could be a potential asset to the pharmaceutical industry, have been least exploited. The present work represents an unprecedented interplay of antimicrobial activity of resorcinarene together with its ability to interact chemically with an antibacterial drug gatifloxacin, improving the overall antibacterial activity. The chemistry and the clinical activities involved in this study were investigated simultaneously by spectroscopic techniques, as well as by in vitro measurement of antibacterial activity toward two human bacterial pathogens, a Gram-positive pathogen Staphylococcus aureus and a Gram-negative lung pathogen Legionella pneumophila. The initial positive result obtained from this study could revolutionize the use of synthetically modifiable resorcinarenes and their analogues in fine tuning the clinical behavior of drugs.

Nucleotide sensing with a perylene-based molecular receptor via amplified fluorescence quenching.

A competitive fluorescence assay of perylene-based molecular receptors has been established, and selective detection of UTP is achieved through improved aggregation arising from the specific interaction of perylene-tethered guanidinium with uridine and phosphate groups in UTP.

Cyclodextrin-assisted synthesis of a metallosupramolecular terbium(III) polymer and its fluorescence properties and chiral recognition.

Hold and connect! Inclusion of a bridging ligand into cyclodextrin (CD), followed by the addition of Tb(III) leads to a polyrotaxane-type metallosupramolecular polymer (see figure, L=4,4'-biphenyldicarboxylic acid). This polymer can recognize chirality and differentiate enantiomers by fluorescence and circular dichroism spectral changes.

Selective detection of NADPH among four pyridine-nucleotide cofactors by a fluorescent probe based on aggregation-induced emission.

A fluorescent sensor based on guanidinium-tethered tetraphenylethene (TPE) has been investigated toward the differentiation of pyridine nucleotide cofactors (NAD(+) , NADH, NADP(+) , and NADPH). TPE selectively recognizes NADPH possessing the higher tetra-anionic net-charge, resulting in the steep "turn-on" fluorescence increase. The comparative aggregation behaviors and fluorescence response studies of TPE on the four cofactors reveal that the critical aggregate concentration of TPE against NADPH correlates directly with the concentration threshold for the fluorescence response. These results establish that TPE can selectively differentiate NADPH over the other three cofactors by the steep aggregation-induced fluorescence response accompanied by the high signal-to-background contrast.

Stereochemistry-dependent, mechanoresponsive supramolecular host assemblies for fullerenes: a guest-induced enhancement of thixotropy.

Self-assembly behaviors of a series of systems (G1, G2, and G3) possessing same organic building blocks based on a substituted anthracene have been investigated in decalin. G2 and G3 are dominated by head-to-tail (ht) and head-to-head (hh) type dimers of G1, respectively. G1 gives a thermoresponsive gel that behaves ideally, showing frequency-independent elastic and viscous moduli. Interestingly, G2 produces a thixotropic gel that shows the signature of structural relaxation, signifying the dynamic nature of the system. In contrast, G3 remains fluidlike. As investigated by scanning electron microscopy (SEM), in the assembly process of G2, first disklike nanoaggregates are formed, and in the second step these aggregates interact to construct the densely packed secondary assembly. A transition from secondary assembly to primary assembly under shear initiates the mechanoresponsive destruction of the gel. In the self-assembly process, G1 propagates in a one-dimensional fashion, whereas G2 and G3 can propagate in a two-dimensionional fashion. The same side orientation of the substituents in G3 facilitates the formation of a compact closed-shell-type structure, which results in the generation of isolated nanocrystals. The long-range weak interaction together with the capability of propagating in two dimensions is found to be essential for the construction of such a mechanoresponsive assembly. C(60) and C(70) could be incorporated successfully in G2 assembly to develop mechanoresponsive fullerene assemblies. The presence of fullerenes not only enhances the elastic properties of G2 but also intensifies the thixotropy. C(70) appears to be a superior guest in terms of property enhancement due to its better size fitting with the concave-shaped host.

Structural alterations of branched versus linear mixed-surfactant micellar systems with the addition of a complex perfume mixture and dipropylene glycol as cosolvent.

Personal care products commonly contain perfume mixtures, consisting of numerous perfume raw materials (PRMs), and cosolvents. The lipophilicity and structure of an individual PRM is known to affect its localization within the surfactant self-assembly as well as the micellar geometry. However, because multiple PRMs are used in formulations, significant intermolecular interactions between the PRMs and between the PRMs and the surfactant tail may also influence the location of the PRMs and their effects on the self-assembly. Herein, two anionic/zwitterionic mixed-surfactant systems (sodium trideceth-2 sulfate (ST2S)/cocamidopropyl betaine (CAPB) and sodium laureth-3 sulfate/CAPB) were formulated with a cosolvent (dipropylene glycol (DPG)) and 12 PRMs of varying structures and lipophilicities. This 12 PRM accord is simpler than a fully formulated perfume but more complex than a single perfume molecule. The geometric variations in the self-assemblies were evaluated using small-angle neutron scattering, perfume head space concentrations were determined using gas chromatography-mass spectrometry, and perfume localization was identified using NMR spectroscopy. The addition of the perfume accord caused enlargement of the micelles in both surfactant systems, with a greater change observed for ST2S/CAPB formulations. Furthermore, the addition of DPG to ST2S/CAPB resulted in micelle shrinkage. The micelle geometries and PRM localization in the micelles were affected by the degree of branching in the surfactant tail.

Structure-Function Correlations in the Mechanism of Action of Key Antiperspirant Agents Containing Al(III) and ZAG Salts.

Aluminum hydrolysis chemistry is an important part of modern society because of the dominance of Al(III) as a highly effective antiperspirant active. However, the century-old chemistry centered on aluminum chloride (ACL) is not comprehensive enough to address all of the in vivo events associated with current commercial antiperspirants and their mechanism of action. The present study aims to address the knowledge gap among extensively studied benchmark ACL, its modified version aluminum chlorohydrate (ACH), and a more complex but less explored group of aluminum zirconium chlorohydrate glycine complexes (ZAG salts) toward understanding the mechanism of action under consumer-relevant conditions. ACH, which is the Al source used in the manufacture of ZAG salts, provides a bridge between ACL and ZAG chemistry. High viscosity and gel formation driven by pH and a specific Al(III) salt upon hydrolysis are considered the criteria for building an in vivo occlusive mass to retard or stop the flow of sweat to the skin surface, thus providing an antiperspirant effect. Rheological studies indicated that ACL and aluminum zirconium tetrachlorohydrex glycine (TETRA) were the most efficacious salt actives. Spectroscopic studies, diffraction studies, and elemental analysis suggested that small metal oxide and hydroxide species with coparticipating glycine as well as various polynuclear and oligomeric species are the key to gel formation. At a given pH, the key ingredients (NaCl, urea, bovine serum albumin, and lactic acid) in artificial sweat were found to have little influence on Al(III) salt hydrolysis. The effects of the sweat components were mostly limited to local complex formation and kinetic modification. The in vitro comparative experiments with various Al(III) and ZAG salt systems offer unprecedented insights into the chemistry of different salt types, thus paving the way for engineering more efficacious antiperspirant systems.

A pH-responsive carboxylic ß-1,3-glucan polysaccharide for complexation with polymeric guests.

The helix-forming nature of ß-1,3-glucan polysaccharides is a characteristic that has potential for producing gene carriers, bio-nanomaterials and other chiral nanowires. Herein, carboxylic curdlan (CurCOOH) bearing the ß-1,3-polyglucuronic acid structure was successfully prepared from ß-1,3-glucan polysaccharide curdlan (Cur) by one-step oxidation using a 4-acetamido-TEMPO/NaClO/NaClO(2) system as the oxidant. The resulting high-molecular-weight CurCOOH was proved to bear the 6-COOH group in 100% purity. The optical rotatory dispersion (ORD) spectra indicated that the obtained CurCOOH behaves as a water-soluble single-strand in various pH aqueous media. This advantage has allowed us to use CurCOOH as a polymeric host to form various macromolecular complexes. For example, complexation of CurCOOH with single-walled carbon nanotubes (SWNTs) resulted in a water-soluble one-dimensional architecture, which formed a dispersion in aqueous solution that was stable for several months, and much more stable than SWNTs complexes of the similar negatively-charged polyacrylic acid (PAA) and polymethacrylic acid (PMAA). It was shown that in the complex, SWNTs are effectively wrapped by a small amount of CurCOOH, enabling them to avoid electrostatic repulsion. This pH-responsive CurCOOH formed a very stable complex with cationic water-soluble polythiophenes (PT-1), which was stabilized not only by the hydrophobic interaction but also by the electrostatic attraction between trimethylammonium cations in PT-1 and dissociated anionic COO(-) groups in CurCOOH. The included PT-1 became CD-active only in the neutral to basic pH region, and the positive Cotton effect suggested that the conjugated main chain is twisted in the right-handed direction. We also found that CurCOOH can interact with polycytidylic acid (poly(C)) only under high NaCl concentrations, the binding and release of which could be controlled by a change in the salt concentration. We believe, therefore, that CurCOOH bearing a dissociable COOH group can act as a new potential polymeric host to construct novel polymeric complexes applicable for gene carriers, biosensors, chiral polymer assemblies, etc.

Investigating the effect of a simplified perfume accord and dilution on the formation of mixed-surfactant microemulsions.

The phase analysis of a mixed surfactant system is much more complex than that for a single surfactant system. The addition of fragrance further enhances the complexity of such colloidal systems. The wide variation in structure and log P values of perfume raw materials influence its partitioning into the micellar phase. Herein, we have created a simplified perfume accord consisting of three perfume raw materials (3-PRM) and investigated its loading within a mixed-surfactant system consisting of sodium trideceth-2 sulfate/ST2S and cocamidopropyl betaine/CAPB, along with citric acid and dipropylene glycol. We performed a systematic phase diagram analysis and identified the isotropic phases and compositions of interest. Select compositions from the phase diagram were further investigated to learn how the geometry of the surfactant self-assembly and the localization of the PRMs within the surfactant self-assembly changed when water or perfume is added. A combined small-angle neutron scattering/SANS and NMR methodology was used to identify variation in colloidal domains and positioning of perfume molecules at varying dilutions/rinse off scenarios. The results obtained were utilized to better distinguish distorted micelles from true microemulsions. The systematic investigation here provides a fundamental understanding about the self-assembly, encapsulation and perfume release from a commercially relevant mixed surfactant system.

Thermo- and solvent-responsive polymer complex created from supramolecular complexation between a helix-forming polysaccharide and a cationic polythiophene.

The helical structure is one of key structural components for both biological systems and artificial chiral systems. So far, we have succeeded in fabricating "tight" insulated molecular wires consisting of a triple-stranded cohelical structure formed through supramolecular wrapping of synthetic polymers by a helix-forming polysaccharide (schizophyllan). Herein, we have designed a new modified polysaccharide (Cur-oeg) to form a "loose" macromolecular complex with a conjugated polymer (CP) that allows structural changes in response to external stimuli. Cur-oeg forms a helical complex with an achiral cationic polythiophene (PT1), and the effective conjugation length is changed by temperature, showing a large absorption peak shift from 403 to 482 nm between 85 and 5 °C. According to the change in the conjugation system, the fluorescence and the induced circular dichroism show the continuous spectral shifts under temperature control. The color changes in the absorption and the fluorescence are detectable with observation by the naked eye and are reversibly controlled under thermal cycles, indicating that this system has the function of a "molecular thermometer". It is shown that the induced thermoresponsiveness is associated with structural rearrangement of the helical conformation of PT1 in the complex. Moreover, another unique responsiveness is discovered for the film state: that is, the film color is varied when it is exposed to the vapor of water or methanol (vaporchromism), resulting from the structural change of PT1 occurring even in the film state. These flexible molecular motions in both the solution state and the film state can be applicable to the design of CP-based smart sensors, polarized materials, switching devices, etc.

Transcription of chirality in the organogel systems dictates the enantiodifferentiating photodimerization of substituted anthracene.

An organogelator (G) that contains 2-anthracenecarboxylic acid (2Ac) attached covalently to a gelator counterpart that consists of 3,4,5-tris(n-dodecan-1-yloxy)benzoic acid by means of a chiral amino alcohol linkage has been synthesized. G acts as an efficient gelator of organic solvents, including mixed solvents and chiral solvents. Photodimers isolated after the photoreaction of the gel samples display different degrees of stereoselectivity. In the gel state, the formation of head-to-head (h-h) photodimers is always favored over head-to-tail (h-t) photodimers. Enantiomeric excess (ee) values of the major h-h photodimers reached as high as -56% in the case of the gels with enantiomeric glycidyl methyl ethers. Here, the solvent chirality is outweighed by the intrinsic chirality of the gelator molecule. The packing of the chromophore in the gel state has been characterized by the absorption and the emission behaviors and their variations during the course of gel-to-sol phase transition. Whereas for the hexane gel, emission intensity increases with an increase in temperature, other systems show a decrease in emission intensity. Redshift of the lambda(max) in the gel spectra indicates the J-aggregate arrangement of the chromophores. Chiral transcription in the gel state has been investigated by CD spectroscopy, which shows a decrease in CD intensity during the gel-to-sol phase transition. The X-ray diffraction study clearly differentiates among the gels in terms of the order of molecular arrangements. The gel systems are categorized as strong, moderately strong, and weak, that originate from the cooperative or individual participations of intermolecular hydrogen-bonding and pi-pi interactions, fine-tuned by the solvent polarity and the gelation temperature. A simple model based on the experimental findings and the molecular preorientation as evidenced by the stereochemistry of the photodimers has been proposed.

Biomolecular hybrid of poly(3-thiophene acetic acid) and double stranded DNA: optical and conductivity properties.

A new biomolecular hybrid of poly(3-thiophene acetic acid) (PTAA) and double stranded deoxyribonucleic acid (ds-DNA) is prepared. The transmission electron microscopy (TEM) images exhibit fibrillar network morphology making a nanostructured self-assembly of PTAA-DNA hybrid. The confocal fluorescence image of PTAA shows green fluorescence exhibiting agglomeration in the pure state but the spreading of green fluorescence over the network superstructure in the hybrids indicating the immobilization of PTAA on DNA surfaces. Fourier transform infrared (FTIR) spectra indicate hydrogen bonding between -COOH groups of PTAA and P=O groups of Na-DNA. Circular dichroism (CD) spectra denote that DNA conformation remains unaltered during hybrid preparation. A blue shift of the pi-pi* absorption peak of PTAA in the hybrid solutions occurs with aging time. The photoluminescence intensity in the hybrid solution increases with a concomitant blue shift of the emission peak with aging time, and it is faster with increased DNA concentration. Possible reasons of different optical behavior are discussed in the light of duplex and triplex hybrid formation. Dynamic light scattering study indicates an increased particle size of PTAA with addition of DNA favoring the hybrid particles to remain in solution. The dc-conductivity of the hybrids decreases from that of PTAA with an increase of Na-DNA concentration, and the current (I)-voltage (V) curves indicate a semiconducting nature of the hybrids.

Conducting Polymer Grafting: Recent and Key Developments.

Since the discovery of conductive polyacetylene, conductive electroactive polymers are at the focal point of technology generation and biocommunication materials. The reasons why this research never stops growing, are twofold: first, the demands from the advanced technology towards more sophistication, precision, durability, processability and cost-effectiveness; and second, the shaping of conducting polymer research in accordance with the above demand. One of the major challenges in conducting polymer research is addressing the processability issue without sacrificing the electroactive properties. Therefore, new synthetic designs and use of post-modification techniques become crucial than ever. This quest is not only advancing the field but also giving birth of new hybrid materials integrating merits of multiple functional motifs. The present review article is an attempt to discuss the recent progress in conducting polymer grafting, which is not entirely new, but relatively lesser developed area for this class of polymers to fine-tune their physicochemical properties. Apart from conventional covalent grafting techniques, non-covalent approach, which is relatively new but has worth creation potential, will also be discussed. The aim is to bring together novel molecular designs and strategies to stimulate the existing conducting polymer synthesis methodologies in order to enrich its fascinating chemistry dedicated toward real-life applications.

An organogel system can control the stereochemical course of anthracene photodimerization.

A novel photoresponsive organogel with a binary gelator containing 2-anthracenecarboxylic acid shows a high degree of stereochemical control, resulting in head-to-head photocyclodimers exclusively together with significant enantiomeric excess induced by the chiral counterpart of the gelator.