Bispidine as a promising scaffold for designing molecular machines.

The development of artificial molecular machines is a challenging endeavor. Herein, we have synthesized a series of bispidine diamides D1-D6 that exhibit rotation reminiscent of a motor motion. Dynamic NMR, X-ray diffraction, quantum mechanical calculations, and molecular dynamics simulations provided insights into their rotational dynamics. All the diamides D1-D6 exhibited mutually independent rotation around the two bispidine arms. However, the rate of rotation and the presence or absence of directionality in amide bond rotation were found to depend on the solvent, temperature, and nature of substitution on the amide carbonyl. These engineered systems may aid in the development of biologically relevant synthetic molecular motors. Studies on homochiral and heterochiral bispidine-peptides revealed that the direction of rotation can be controlled by chirality and the nature of the amino acid.

Picosecond spin-orbit torque-induced coherent magnetization switching in a ferromagnet.

Electrically controllable nonvolatile magnetic memories show great potential for the replacement of conventional semiconductor-based memory technologies. Here, we experimentally demonstrate ultrafast spin-orbit torque (SOT)-induced coherent magnetization switching dynamics in a ferromagnet. We use an ultrafast photoconducting switch and a coplanar strip line to generate and guide a ~9-picosecond electrical pulse into a heavy metal/ferromagnet multilayer to induce ultrafast SOT. We then use magneto-optical probing to investigate the magnetization dynamics with sub-picosecond resolution. Ultrafast heating by the approximately 9 picosecond current pulse induces a thermal anisotropy torque which, in combination with the damping-like torque, coherently rotates the magnetization to obtain zero-crossing of magnetization in ~70 picoseconds. A macro-magnetic simulation coupled with an ultrafast heating model agrees well with the experiment and suggests coherent magnetization switching without any incubation delay on an unprecedented time scale. Our work proposes a unique magnetization switching mechanism toward markedly increasing the writing speed of SOT magnetic random-access memory devices.

Bispidine as a Versatile Scaffold: From Topological Hosts to Transmembrane Transporters.

The development of designer topological structures is a synthetically challenging endeavor. We present herein bispidine as a platform for the design of molecules with various topologies and functions. The bispidine-based acyclic molecule, which shows intriguing S-shape topology, is discussed. Single-crystal X-ray diffraction studies revealed that this molecule exists in the solid state as two conformational enantiomers. In addition, bispidine-based designer macrocycles were synthesized and investigated for ionophoric properties. Patch clamp experiments revealed that these macrocycles transport both anions and cations non-specifically with at least tenfold higher chloride conductance over the cations under the given experimental conditions. Ultramicroscopy and single-crystal X-ray crystallographic studies indicated that the self-assembling macrocycle forms a tubular assembly. Our design highlights the use of unconventional dihydrogen interactions in nanotube fabrication.

Energy Efficient All-Electric-Field-Controlled Multiferroic Magnetic Domain-Wall Logic.

Magnetic domain wall (DW)-based logic devices offer numerous opportunities for emerging electronics applications allowing superior performance characteristics such as fast motion, high density, and nonvolatility to process information. However, these devices rely on an external magnetic field, which limits their implementation; this is particularly problematic in large-scale applications. Multiferroic systems consisting of a piezoelectric substrate coupled with ferromagnets provide a potential solution that provides the possibility of controlling magnetization through an electric field via magnetoelastic coupling. Strain-induced magnetization anisotropy tilting can influence the DW motion in a controllable way. We demonstrate a method to perform all-electrical logic operations using such a system. Ferromagnetic coupling between neighboring magnetic domains induced by the electric-field-controlled strain has been exploited to promote noncollinear spin alignment, which is used for realizing essential building blocks, including DW generation, propagation, and pinning, in all implementations of Boolean logic, which will pave the way for scalable memory-in-logic applications.

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.

Pseudopeptosomes: non-lipidated vesicular assemblies from bispidine-appended pseudopeptides.

We report a novel molecular topology-based approach for creating reproducible vesicular assemblies in different solvent environments (including aqueous) using specifically designed pseudopeptides. Deviating from the classical "polar head group and hydrophobic tail" model of amphiphiles, we showed (reversible) self-assembly of synthesized pseudopeptides into vesicles. Naming these new type/class of vesicles "pseudopetosomes", we characterized them by high-resolution microscopy (scanning electron, transmission electron, atomic force, epifluorescence and confocal) along with dynamic light scattering. While accounting for hydropathy index of the constituent amino acids (side chains) of pseudopeptides, we probed molecular interactions, resulting in assembly of pseudopeptosomes by spectroscopy (fourier-transform infrared and fluorescence). Molecular characterization by X-ray crystallography and circular dichroism revealed "tryptophan (Trp)-Zip" arrangements and/or hydrogen-bonded one-dimensional assembly depending on specific pseudopeptides and solvent environments. Our data indicated that pseudopeptosomes are formed in solutions by self-assembly of bispidine pseudopeptides (of Trp, leucine and alanine amino-acid constituents) into sheets that transform into vesicular structures. Thus, we showed that assembly of pseudopeptosomes utilizes the full spectrum of all four weak interactions essential in biological systems. Our findings have direct implications in chemical and synthetic biology, but may also provide a new avenue of investigations on origins of life via pseudopeptosome-like assemblies. We also showed that these designer peptides can act as carriers for cellular transport.

Liquid crystal droplet design by using pseudopeptidic bottlebrush polymer additives.

Liquid crystal (LC) droplets are promising candidates for sensing applications due to their high sensitivity to surface anchoring changes, resulting in readily detectable optical effects. Herein, we have designed and synthesized amino acid-based bottlebrush polymers and investigated their impact on LC director configurations in the droplets. The pseudopeptidic bottlebrush polymers with an aromatic (phenyl) and aliphatic appendages are synthesized using ring-opening metathesis polymerization (ROMP). Polymer dispersed liquid crystal (PDLC) samples are prepared by employing pseudopeptidic bottlebrush polymers and 4-cyano-4'-pentylbiphenyl (5CB) LC via solvent-induced phase separation (SIPS) technique. Due to π-π stacking, the phenyl group favours radial configuration, whereas the repulsion between 5CB and aliphatic groups induces molecular alignment leading to bipolar droplet arrangement. The impact of various pendant groups attached to the polymer on the prepared PDLC sample's surface characteristics and free energy components is illustrated. The sensing capability of 5CB dispersed in pseudopeptidic bottlebrush polymers for various pH solutions is investigated using polarizing optical microscopy (POM). The PDLC samples are moderately permeable to water and sensitive to different pH solutions. The results demonstrate a simplified and straightforward approach for preparing LC-based biosensors and chemical sensors.

Molecular Insights into the Inhibition of Dialysis-Related ß2m Amyloidosis Orchestrated by a Bispidine Peptidomimetic Analogue.

Dialysis-related amyloidosis (DRA) is considered an inescapable consequence of renal failure. Upon prolonged hemodialysis, it involves accumulation of toxic ß2-microglobulin (ß2m) amyloids in bones and joints. Current treatment methods are plagued with high cost, low specificity, and low capacity. Through our in vitro and in cellulo studies, we introduce a peptidomimetic-based approach to help develop future therapeutics against DRA. Our study reports the ability of a nontoxic, core-modified, bispidine peptidomimetic analogue "B(LVI)2" to inhibit acid-induced amyloid fibrillation of ß2m (Hß2m). Using thioflavin-T, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and transmission electron microscopy analysis, we demonstrate that B(LVI)2 delays aggregation lag time of Hß2m amyloid fibrillation and reduces the yield of Hß2m amyloid fibrils in a dose-dependent manner. Our findings suggest a B(LVI)2-orchestrated alteration in the route of Hß2m amyloid fibrillation resulting in the formation of noncytotoxic, morphologically distinct amyloid-like species. Circular dichroism data show gradual sequestration of Hß2m species in a soluble nonamyloidogenic noncytotoxic conformation in the presence of B(LVI)2. Dynamic light scattering measurements indicate incompetence of Hß2m species in the presence of B(LVI)2 to undergo amyloid-competent intermolecular associations. Overall, our study reports the antifibrillation property of a novel peptidomimetic with the potential to bring a paradigm shift in therapeutic approaches against DRA.

Ratiometric Recognition of Protons by a Multiple Tagged Designer Fluorescent Chemosensor.

Molecular architecture with different fluorophoric units can offer improved and effective recognition of biologically important analytes. We present here a new strategy for the design of ratiometric chemosensors that operate by photoinduced electron transfer (PET). This ratiometric sensor endowed with tryptophan and anthracene exhibits high sensitivity, excellent selectivity and remarkable reversibility towards recognition of H+ in methanol. This "Turn-On" type behaviour is crafted into the molecule by incorporation of bispidine entity. Effective quenching of the fluorescence of the anthracene by the adjacent amine groups of the bispidine results in negligible fluorescence from the anthracene group leading to highly sensitive recognition of protons by the compound as H+ protonate the amine functionalities giving rise to the emergence of the fluorescence from the anthracene group. This, combined with the reduction in the fluorescence from the Trp group by H+, results in highly sensitive ratiometric nature of the response especially at low [H+].

Designer peptides as versatile building blocks for functional materials.

Peptides and pseudopeptides show distinct self-assembled nanostructures such as fibers, nanotubes, vesicles, micelles, toroids, helices and rods. The formation of such molecular communities through the collective behavior of molecules is not fully understood at a molecular level. All these self-assembled nanostructured materials have a wide range of applications such as drug delivery, gene delivery, biosensing, bioimaging, catalysis, tissue engineering, nano-electronics and sensing. Self-assembly is one of the most efficient and a simple strategy to generate complex functional materials. Owing to its significance, the last few decades witnessed a remarkable advancement in the field of self-assembling peptides with a plethora of new designer synthetic systems being discovered. These systems range from amphiphilic, cyclic, linear and polymeric peptides. This article presents only selected examples of such self-assembling peptides and pseudopeptides.

Supersensitive Detection of Anions in Pure Organic and Aqueous Media by Amino Acid Conjugated Ellman's Reagent.

The last few decades witnessed a remarkable advancement in the field of molecular anion receptors. A variety of anion binding motifs have been discovered, and large number of designer molecular anion receptors with high selectivity are being reported. However, anion detection in an aqueous medium is still a formidable challenge as evident from only a miniscule of synthetic systems available in the literature. We, herein, report 5,5'-dithio-bis(2-nitrobenzoic acid) (Ellman's reagent) appended with amino acids as supersensitive anion sensors that can detect F- and H2PO4- ions in both aqueous as well as organic media. Interestingly, the sensors showed a dual response to anions, viz., chromogenic response in organic medium and electrochemical response in aqueous solutions. Various spectroscopic techniques such as UV-vis and 1H NMR are used to investigate the binding studies in acetonitrile, whereas electrochemical methods such as cyclic voltammetry (CV) and differential pulse voltammetry (DPV) are employed to explore the anion binding in water. The host-guest complex stoichiometry and binding constants are calculated using the BindFit software. The geometry of host-guest complex has been optimized by the density functional theory (DFT) method. These molecules are versatile sensors since these function in both water and acetonitrile with extremely low limit of detection (LOD) up to 0.07 fM and limit of quantification (LOQ) up to 0.23 fM. To our knowledge, the present system is the first example of a sensor that can detect the lowest concentration of anions in water quantitatively. The minimalistic design strategy presented here opens up the innumerable possibilities for designing dual anion sensors in a one fell swoop.

Bispidine as a ß-strand nucleator: from a ß-arch to self-assembled cages and vesicles.

The development of synthetic scaffolds that nucleate well-folded secondary structures is highly challenging. Herein, we designed and synthesized a series of core-modified peptides (F1, F2, F3, and F4) that fold into ß-strand structures. These bispidine-scaffolded peptides were studied by CD, IR, NMR, single crystal XRD, and Molecular Dynamics (MD) simulations to investigate their conformational preferences. Solid-state and solution studies revealed that bispidine is a versatile scaffold that could be placed either at the terminal or at the middle of the peptide strand for nucleating the ß-strand structure. Scaffolds that nucleate an isolated ß-strand conformation are rare. Bispidine placed at the C-terminus of the peptide chain could nucleate a ß-strand conformation, while bispidine placed at the middle resulted in a ß-arch conformation. This nucleation activity stems from the ability to restrict the psi torsion angle (ψ) through intramolecular C5 hydrogen bonding between the equatorial hydrogen(s) of bispidine and the carbonyl oxygen(s) of the amino acid close to the scaffold. Furthermore, the bispidine peptidomimetic with a super secondary structure, namely ß-arch, assembled into single-hole submicron cages and spherical vesicles as evident from microscopic studies. The design logic defined here will be a significant strategy for the development of ß-strand mimetics and super secondary structures.

Unprecedented formation of reverse micellar vesicles from psuedopeptidic bottlebrush polymers.

Spherical assemblies named "reverse micellar vesicles" from self-assembling psuedopeptidic bottlebrush polymers are reported. These assemblies exhibited the combined features of both micelles and vesicles viz. molecular arrangement of classical micelles and dimensions similar to that of classical vesicles. Comprehensive ultramicroscopic and spectroscopic analyses were performed to delineate the hierarchical mechanism of their formation.

Revealing Signs and Hidden 1H NMR Coupling Constants in Three-Spin Systems Using Long-Lived Coherences.

Long-lived coherences (LLCs) in a pair of coupled protons have long lifetimes and hence decreased line width and increased spectral resolution. Fourier transformation of the damped oscillatory decay of the LLC also provides coupling information on the spin system. In a three-spin system, unlike in the two-spin case, the peaks in an LLC spectrum are observed at combinations of the coupling constants. This attribute is used to determine the relative signs of the coupling constants in weakly and strongly coupled model systems. In addition, it is shown that a coupling constant in a three-spin system that is unobservable in the 1H NMR spectrum, as is the case in bispidinone, a molecule of significance in peptidomimetics, may be determined from the LLC spectrum.

Unprecedented Intramolecular Association-Induced Fluorescence in Tryptophan-Conjugated Peptidomimetics.

We report herewith tryptophan (Trp)-conjugated peptidomimetics that show intramolecular through-space association between the Trp units. Our investigation revealed that the proximal placement of Trp can lead to the emergence of a new and unanticipated fluorescent entity constituting a Trp-Trp dimer. Proton-induced modulation of fluorescence is a consequence of this work. Investigations with control compounds unequivocally revealed that the fluorescence property is not originated from the localized excited state but from the unprecedented Trp-Trp intramolecular dimer in the ground state itself. The present findings will initiate the biophysical scientists to have a relook at the fluorescence properties of Trp-containing proteins.

Gyrator Based on Magneto-elastic Coupling at a Ferromagnetic/Piezoelectric Interface.

A gyrator is a non-reciprocal two port device with 180° phase shift in the transmissions between two ports. Though electromagnetic realizations of gyrators have been well studied, devices based on other forms of interaction are relatively unexplored. Here we demonstrate a device in which signal is transmitted via magneto-elastic coupling, can function as a gyrator. The device is built on a piezoelectric substrate: one port of this device has interdigital transducers (IDTs) and the other port has a periodic array of nickel/gold lines. When the magnetizations of Ni lines are excited into precession by magnetic field generated by passing oscillating current through the gold lines, they emit phonons in the form of surface acoustic waves (SAW) due to the magneto-elastic coupling between Ni and substrate. The emitted SAW can be detected at the other end by the IDTs. Conversely, when SAW is incident on Ni lines from IDTs, the magnetization undergoes precession and can be inductively detected by Au lines. The broken time reversal symmetry of the system due to the presence of ferromagnet gives rise to the non-reciprocal transmission between the two ports. These devices could function as novel building blocks for phonon based information processing.