Expanded triazolophanes: a topological analysis of vesicular assembly.

Triazolophanes with larger ring sizes such as 40- and 42- were designed and synthesized. Ultramicroscopic studies on a variety of expanded triazolophanes and larger acyclic systems revealed vesicular self-assembly. The role of molecular topology on vesicular assembly was systematically investigated by studying a series of molecules with increasing curvature.

Highly Efficient Intramolecular Excimer Formation in a Disulfide-Linked Dipyrenyl Compound: Proton Recognition and Fluidity Assessment.

Intramolecular excimer formation has been utilized extensively in chemical sciences, especially to probe solvation within complex media as well as to assess physicochemical properties of the solubilizing milieu. Pyrene has been employed extensively as a fluorescence probe for this purpose due to its favorable multidimensional fluorescence properties. Termini-capped dipyrenyl scaffolds possessing various functionalities comprise the majority of such compounds. A new both end-tagged dipyrenyl compound DTP is designed and synthesized, which exhibits significantly high intramolecular excimer formation efficiency in polar solvents. The presence of a -NH-(CO)- and/or -S-S- functionality on the chain linking the two pyrenyl groups facilitates intramolecular excimer formation. Excited-state emission intensity decay reveals that the excimer formation exclusively takes place in the excited state with only one excimer conformation. The rate constant of excimer formation is found to be higher for DTP as compared to a similar compound with an alkyl backbone. The dependence of the excimer formation on the solvent (protic versus aprotic) as well as on temperature reveals further insights into the excimer formation process. The excimer formation by DTP is found to be highly sensitive to the presence of H+: the relative excimer formation efficiency decreases drastically in the presence of a small amount of H+ (∼10-5 M). Further, the recognition of protons by DTP via intramolecular excimer formation is also observed to be highly selective in nature. Based on the observation that both the excimer formation efficiency and kinetics depend on the viscosity of the solubilizing milieu, fluidity assessment of the (dimethyl sulfoxide + acetonitrile) mixture was carried out using DTP. Further, DTP is found to be an effective probe for the assessment of the amount of water in the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide as well as in a deep eutectic solvent composed of choline chloride and urea in a 1:2 mol ratio. Highly efficient and rapid intramolecular excimer formation not only establishes DTP as a useful and versatile probe but also offers strategic pathways for designing effective excimer-forming compounds.

Hydrophobicity Directed Chiral Self-Assembly and Aggregation-Induced Emission: Diacetylene-Cored Pseudopeptide Chiral Dopants.

Here we delineate simple and tunable hydrophobically driven chiral functional assemblies of diacetylene cored pseudopeptides. These amino acid appended, rigid core dialkynes constitute promising chiral supramolecular building blocks for materials properties engineering. The chiral appended amino acid elements allow for simple tuning of solubility and interaction properties as well as governing chirality, while the central dialkyne core can impart hydrophobically driven assembly and Aggregation Induced Emission (AIE) properties. The self-assembly of these rod-like dialkynes can be regulated by tuning the solvent environment, with for example self-assembly into vesicles in acetonitrile and into helical organization with AIE in a H2 O/DMSO mixture. Of additional high interest, these supramolecular materials, themselves devoid of liquid crystal (LC) properties, can induce chirality into non-chiral LC matrices with high helical twisting power.

Designer Peptide and Protein Dendrimers: A Cross-Sectional Analysis.

Dendrimers have attracted immense interest in science and technology due to their unique chemical structure that offers a myriad of opportunities for researchers. Dendritic design allows us to present peptides in a branched three-dimensional fashion that eventually leads to a globular shape, thus mimicking globular proteins. Peptide dendrimers, unlike other classes of dendrimers, have immense applications in biomedical research due to their biological origin. The diversity of potential building blocks and innumerable possibilities for design, along with the fact that the area is relatively underexplored, make peptide dendrimers sought-after candidates for various applications. This review summarizes the stepwise evolution of peptidic dendrimers along with their multifaceted applications in various fields. Further, the introduction of biomacromolecules such as proteins to a dendritic scaffold, resulting in complex macromolecules with discrete molecular weights, is an altogether new addition to the area of organic chemistry. The synthesis of highly complex and fully folded biomacromolecules on a dendritic scaffold requires expertise in synthetic organic chemistry and biology. Presently, there are only a handful of examples of protein dendrimers; we believe that these limited examples will fuel further research in this area.

Peptide Dendrons as Thermal-Stability Amplifiers for Immunoglobulin G1 Monoclonal Antibody Biotherapeutics.

Biotherapeutics such as monoclonal antibodies (mAbs) have a major share of the pharmaceutical industry for treatment of life-threatening chronic diseases such as cancer, skin ailments, and immune disorders. Instabilities such as aggregation, fragmentation, oxidation, and reduction have resulted in the practice of storing these products at low temperatures (-80 to -20 °C). However, reliable storage at these temperatures can be a challenge, particularly in developing and underdeveloped countries; hence, lately, there has been a renewed interest in creating formulations that would offer stability at higher temperatures (25 to 55 °C). Most therapeutic formulations contain excipients such as salts, sugars, amino acids, surfactants, and polymers to provide stability to the biotherapeutic, but their efficacy at high temperatures is limited. The current work proposes the use of peptide dendrons of different generations to create formulations that would be stable at high temperature. Among these dendrons, third-generation lysine dendron L6 has been identified to provide the highest stability to mAbs, as demonstrated by a host of analytical techniques such as size-exclusion chromatography (SEC), dynamic light scattering (DLS), Nanoparticle tracking Analysis (NTA), and circular dichroism (CD). The biocompatibility of these dendrons was confirmed by hemolytic activity tests. Non-interference of the dendrons with the activity of the mAb was confirmed using a surface plasmon resonance (SPR) based activity assay. We hope that this study will stimulate utilization of such higher-generation dendrons for enhancing the thermal stability of mAbs.

Chemical Biology of Sortase A Inhibition: A Gateway to Anti-infective Therapeutic Agents.

Staphylococcus aureus is the leading cause of hospital-acquired infections. The enzyme sortase A, present on the cell surface of S. aureus, plays a key role in bacterial virulence without affecting the bacterial viability. Inhibition of sortase A activity offers a powerful but clinically less explored therapeutic strategy, as it offers the possibility of not inducing any selective pressure on the bacteria to evolve drug-resistant strains. In this Perspective, we offer a chemical space narrative for the design of sortase A inhibitors, as delineated into three broad domains: peptidomimetics, natural products, and synthetic small molecules. This provides immense opportunities for medicinal chemists to alleviate the ever-growing crisis of antibiotic resistance.