Cucurbit[7]uril Induced Formation of FRET-Enabled Unilamellar Lipid Vesicles.

A unique fluorescence resonance energy transfer (FRET) process is found to be operational in a unilamellar lipid self-assembly in the aqueous phase. A newly synthesized naphthyl based long chain lipid derivative [N-(naphthalene-1-ylmethyl)tetradecane-1-ammonium chloride, 14NA+] forms various self-assembled architectures in the aqueous phase. Controlled changes in lipid concentration lead to a transition of the self-assemblies from micelles to vesicles to rods. In the presence of cucurbit[7]uril (CB7), 14NA+ forms a host-guest [2]pseudorotaxane complex (CB7∋14NA+) and secondary interactions lead to the formation of a lipid bilayer with hydrophobic pockets situated in between the layers. The change in the structure of 14NA+ assemblies, interaction with CB7 and formation of supramolecular assemblies of CB7∋14NA+ were examined using light scattering, spectroscopic, and microscopic techniques. Entrapment of a luminescent dye, anthracene within the hydrophobic bilayer of the supramolecular assembly CB7∋14NA+ favors a modified luminescent response due to an efficient FRET process. Further, the FRET process could be controlled by thermal and chemical stimuli that induce transformation of unilamellar vesicles.

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity.

Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N+···Fδ- charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

Secondary Interactions Arrest the Hemiaminal Intermediate To Invert the Modus Operandi of Schiff Base Reaction: A Route to Benzoxazinones.

Discovered by Hugo Schiff, condensation between amine and aldehyde represents one of the most ubiquitous reactions in chemistry. This classical reaction is widely used to manufacture pharmaceuticals and fine chemicals. However, the rapid and reversible formation of Schiff base prohibits formation of alternative products, of which benzoxazinones are an important class. Therefore, manipulating the reactivity of two partners to invert the course of this reaction is an elusive target. Presented here is a synthetic strategy that regulates the sequence of Schiff base reaction via weak secondary interactions. Guided by the computational models, reaction between 2,3,4,5,6-pentafluoro-benzaldehyde with 2-amino-6-methylbenzoic acid revealed quantitative (99%) formation of 5-methyl-2-(perfluorophenyl)-1,2-dihydro-4H-benzo[d][1,3]oxazin-4-one (15). Electron donating and electron withdrawing ortho-substituents on 2-aminobenzoic acid resulted in the production of benzoxazinones 9-36. The mode of action was tracked using low temperature NMR, UV-vis spectroscopy, and isotopic (18O) labeling experiments. These spectroscopic mechanistic investigations revealed that the hemiaminal intermediate is arrested by the hydrogen-bonding motif to yield benzoxazinone. Thus, the mechanistic investigations and DFT calculations categorically rule out the possibility of in situ imine formation followed by ring-closing, but support instead hydrogen-bond assisted ring-closing to prodrugs. This unprecedented reaction represents an interesting and competitive alternative to metal catalyzed and classical methods of preparing benzoxazinone.

Oxidative Intramolecular 1,2-Amino-Oxygenation of Alkynes under AuI /AuIII Catalysis: Discovery of a Pyridinium-Oxazole Dyad as an Ionic Fluorophore.

Oxidative intramolecular 1,2-amino-oxygenation reactions, combining gold(I)/gold(III) catalysis, is reported. The reaction provides efficient access to a structurally unique ionic pyridinium-oxazole dyad with tunable emission wavelengths. The application of these fluorophores as potential biomarkers has been investigated.

Silk Fibroin-Sophorolipid Gelation: Deciphering the Underlying Mechanism.

Silk fibroin (SF) protein, produced by silkworm Bombyx mori, is a promising biomaterial, while sophorolipid (SL) is an amphiphilic functional biosurfactant synthesized by nonpathogenic yeast Candida bombicola. SL is a mixture of two forms, acidic (ASL) and lactonic (LSL), which when added to SF results in accelerated gelation of silk fibroin. LSL is known to have multiple biological functionalities and hence hydrogels of these green molecules have promising applications in the biomedical sector. In this work, SANS, NMR, and rheology are employed to examine the assembling properties of individual and mixed SLs and their interactions with SF to understand the mechanism that leads to rapid gelation. SANS and NMR studies show that ASL assembles to form charged micelles, while LSL forms micellar assemblies and aggregates of a mass fractal nature. ASL and LSL together form larger mixed micelles, all of which interact differently with SF. It is shown that preferential binding of LSL to SF causes rapid unfolding of the SF chain leading to the formation of intermolecular beta sheets, which trigger fast gelation. Based on the observations, a mechanism for gelation of SF in the presence of different sophorolipids is proposed.

Tuning Emission Responses of a Triphenylamine Derivative in Host-Guest Complexes and an Unusual Dynamic Inclusion Phenomenon.

A newly synthesized triphenylamine derivative (1Cl3) shows significant differences in inclusion complex formation with two different macrocyclic hosts, cucurbit[7]uril (CB[7]) and ß-cyclodextrin (ß-CD). Detailed investigations by NMR spectroscopy reveal that CB[7] forms a 1:3 host-guest complex ([1·3{CB[7]}]Cl3) in which three arms of 1Cl3 are bound to three host molecules. On the other hand, ß-CD forms a dynamic 1:1 inclusion complex ([1·{ß-CD}]Cl3) by binding to only one of the three arms of 1Cl3 at a given time. The formation of a 1:1 host-guest complex with ß-CD and 1:3 host-guest complex with CB[7] was also confirmed from the results of the isothermal titration calorimetric studies. Interestingly, 1Cl3 exhibits a rare dual emission property in solution at room temperature with the lower and higher energy bands arising from a locally excited state and an intramolecular charge-transfer transition, respectively. The difference in inclusion complex formation behavior of 1Cl3 with the two macrocyclic hosts results in the stabilization of different emission states in the two inclusion complexes. The fundamental difference in the electrostatic surface potentials, cavity polarities, and shapes of the two macrocyclic hosts could account for the formation of the different inclusion complexes with distinct luminescence responses.

Conformational modulation of peptides using ß-amino benzenesulfonic acid ((S)Ant).

This communication describes the utility of a conformationally restricted aromatic ß-amino acid (2-aminobenzenesulfonic acid, (S)Ant) inducing various folding interactions in short peptides. Sandwiching (S)Ant between diverse amino acid residues was shown to form robust folded architectures featuring a variety of H-bonded networks, suggesting its utility in inducing peptide folding.

Reversal of H-bonding direction by N-sulfonation in a synthetic reverse-turn peptide motif.

This communication depicts an intriguing example of hydrogen-bonding reversal upon introduction of a sulfonamide linkage at the N-terminus of a synthetic reverse-turn peptide motif. The ready availability of two sulfonyl oxygen atoms, as hydrogen-bonding acceptors, combined with the inherent twisted conformation of sulfonamides are seen to act as switches that engage/disengage the hydrogen-bond at the sticky ends/termini.

Formation of a pseudo-ß-hairpin motif utilizing the Ant-Pro reverse turn: consequences of stereochemical reordering.

Herein, we report a special case of pseudo-ß-hairpin formation by tetrapetide sequences featuring a two-membered Ant-Pro dipeptide motif (Ant = anthranilic acid and Pro = proline) at the loop region. These folded structures uniquely feature the presence of C9- and C17-H-bonding patterns at reverse turn and interstrand regions, respectively. Their hairpin nucleation and folding propensities have been expounded using solution and solid state studies of distinct stereochemically altered sequences.

A synthetic zipper peptide motif orchestrated via co-operative interplay of hydrogen bonding, aromatic stacking, and backbone chirality.

Here, we report on a new class of synthetic zipper peptide which assumes its three-dimensional zipper-like structure via a co-operative interplay of hydrogen bonding, aromatic stacking, and backbone chirality. Structural studies carried out in both solid- and solution-state confirmed the zipper-like structural architecture assumed by the synthetic peptide which makes use of unusually remote inter-residual hydrogen-bonding and aromatic stacking interactions to attain its shape. The effect of chirality modulation and the extent of noncovalent forces in the structure stabilization have also been comprehensively explored via single-crystal X-ray diffraction and solution-state NMR studies. The results highlight the utility of noncovalent forces in engineering complex synthetic molecules with intriguing structural architectures.

Switching the H-bonding network of a foldamer by modulating the backbone chirality and constitutional ratio of amino acids.

This communication describes the folding propensity of a heterofoldamer motif featuring proline (Pro) and anthranilic acid (Ant) residues in a 1:2:1 (α:ß:α) constitutional ratio. Structural investigations unequivocally suggest that the hydrogen-bonding network of this foldamer motif can be switched between 9-membered and 6-membered by modulating the backbone chirality and constitutional ratio of the amino acid residues.

Ester vs. amide on folding: a case study with a 2-residue synthetic peptide.

Although known for their inferiority as hydrogen-bonding acceptors when compared to amides, esters are often found at the C-terminus of peptides and synthetic oligomers (foldamers), presumably due to the synthetic readiness with which they are obtained using protected peptide coupling, deploying amino acid esters at the C-terminus. When the H-bonding interactions deviate from regularity at the termini, peptide chains tend to "fray apart". However, the individual contributions of C-terminal esters in causing peptide chain end-fraying goes often unnoticed, particularly due to diverse competing effects emanating from large peptide chains. Herein, we describe a striking case of a comparison of the individual contributions of C-terminal ester vs. amide carbonyl as a H-bonding acceptor in the folding of a peptide. A simple two-residue peptide fold has been used as a testing case to demonstrate that amide carbonyl is far superior to ester carbonyl in promoting peptide folding, alienating end-fraying. This finding would have a bearing on the fundamental understanding of the individual contributions of stabilizing/destabilizing non-covalent interactions in peptide folding.

Transition-metal-free multicomponent reactions involving arynes, N-heterocycles, and isatins.

Mix and match: With isoquinoline as the nucleophilic trigger, multicomponent reactions afforded spirooxazino isoquinoline derivatives, proceeding through 1,4-dipolar intermediates. The use of pyridine as a nucleophile furnished indolin-2-one derivatives, with the reaction likely proceeding through a pyridylidene intermediate.

Synthesis and structural characterization of homochiral homo-oligomers of parent cis- and trans-furanoid-ß-amino acids.

The synthesis of homochiral homo-oligomers of cis- and trans-3-aminotetrahydrofuran-2-carboxylic acids (parent cis- and trans-furanoid-ß-amino acids, referred to as "cis-/trans-FAA") has been carried out to understand their secondary structures and their dependence on the ring heteroatom. The oligomers of two diastereomers have been shown to have a distinct left-handed helicity. The cis-FAA homo-oligomers show a 14-helix structure, in contrast to the homo-oligomers of cis-ACPC, which adopt a sheet like structure. The trans-FAA homo-oligomers were found to adopt a 12-helix structure, the same trend found in trans-ACPC homo-oligomers. With the help of ab initio calculations, the structural features of cis-ACPC and cis-FAA hexamers were compared. We believe that the more compact packing of the cis-FAA hexapeptide should be due to a more favorable interaction between the ring and the backbone amide hydrogen.

Concurrent display of both α- and ß-turns in a model peptide.

This article describes a model peptide that concurrently displays both α- and ß-turns, as demonstrated by structural investigations using single crystal X-ray crystallography and solution-state NMR studies. The motif reported herein has the potential for the design of novel conformationally ordered synthetic oligomers with structural architectures distinct from those classically observed.

Charge transfer liquid: a stable donor-acceptor interaction in the solvent-free liquid state.

Charge-transfer complexes have been an inspiration to develop many functional soft materials. However, most of those studies have focused on solution based assemblies wherein the explicit control of solvents and their polarity are crucial. In this context, we explore an efficient and stable charge transfer liquid using a solvent-free liquid dialkoxynaphthalene donor and a naphthalenediimide acceptor. It has been observed that irrespective of the donor-acceptor ratio, the charge-transfer liquid exhibited an unprecedented stability and retained characteristic features even at increased temperatures. The underlying intermolecular interactions leading to efficient CT have been examined by NMR techniques together with theoretical modelling studies. The concept of charge transfer liquid will be highly beneficial for the development of processable optoelectronically active materials.

Foldamers with unusual structural architecture from spirobi(indane) building blocks.

This communication demonstrates the utility of inherently rigid building blocks such as 1,1'-spirobi(indane) for generating conformationally ordered synthetic oligomers with structural architectures distinct from those classically observed.

Self-Assembly of Fluorinated Sugar Amino Acid Derived α,γ-Cyclic Peptides into Transmembrane Anion Transport.

Syntheses of fluorinated sugar amino acid derived α,γ-cyclic tetra- and hexapeptides are reported. The IR, NMR, ESI-MS, CD, and molecular modeling studies of cyclic tetra- and hexapeptides showed C2 and C3 symmetric flat oval- and triangular-ring shaped ß-strand conformations, respectively, which appear to self-assemble into nanotubes. The α,γ-cyclic hexapeptide (EC50 = 2.14 µM) is found to be a more efficient ion transporter than α,γ-cyclic tetrapeptide (EC50 = 14.75 µM). The anion selectivity and recognition of α,γ-cyclic hexapeptide with NO3- ion is investigated.

Angiotensin II analogs comprised of Pro-Amb (γ-turn scaffold) as angiotensin II type 2 (AT(2)) receptor agonists.

We describe herein the design, synthesis and conformational investigation of Pro-Amb (proline-3-amino-2-methoxybenzoic acid) incorporated Angiotensin II and its truncated analogues. Solution-state NMR and CD studies suggest γ-turn-like conformation in Pro-Amb analogs in aqueous solution. Furthermore, Pro-Amb analogs have been shown to act as AT2 receptor agonists.

Supramolecular transitions in native cellulose-I during progressive oxidation reaction leading to quasi-spherical nanoparticles of 6-carboxycellulose.

Cellulose-I swells considerably in phosphoric acid, and converts to amorphous cellulose via a cellulose-II transition state. Controlled oxidation of cellulose-I to 6-carboxycellulose (6 CC) using HNO3-H3PO4-NaNO2 oxidation system led to the selective production of 6 CC's of varying carboxyl contents (1.7-22%) as well as various shapes and sizes (macro-sized fibrils of several micron length and/or spherical nanoparticles of 25-35 nm), depending on the reaction conditions. 6 CC's having less than 14% carboxyl content were largely in cellulose-II form (WAXRD values in-between cellulose I and cellulose II), whereas at 14-22% the 6 CC's were largely amorphous; only trace crystallinity was observed at 19% and 22% carboxyl 6 CC. Spherical nanoparticles retained a high degree of crystallinity having cellulose-I structure, whereas the macro-sized fibrils were largely converted to cellulose-II structure. Analysis by WAXRD as well as by CP-MAS (13)C NMR studies gave similar conclusions. Reduced molecular weight with progressive oxidation, including presence of oligomers, was also evident from an increase in the reducing-end carbon peak at ∼ 92 ppm. For high oxidation levels (>14%) the NMR 92-96 ppm peaks disappeared on extracting with dilute alkali, due to soluble oligomers being removed.