Cucurbit[7]uril Complexation Drives Thermal trans–cis‐Azobenzene Isomerization and Enables Colorimetric Amine Detection

Complexation of yellow diaminoazobenzenes 1 and 3 inside cucurbit[7]uril (CB[7]) results in the formation of purple‐colored CB[7] ? cis‐ 1? 2 H⁺ and CB[7] ? cis‐ 3? 2 H⁺ complexes, respectively. The high binding affinity and selectivity displayed by CB[7] toward 1 and 3 pays the >10 kcal mol^?1 thermodynamic cost for this isomerization. We investigated the behavior of these complexes as a function of pH and observed large pK_a shifts and high pH responsiveness, which are characteristic of cucurbit[n]uril molecular containers. The remarkable yellow to purple color change was utilized in the construction of an indicator displacement assay for biologically active amines 4 – 10 . This indicator displacement assay is capable of quantifying the pseudoephedrine ( 5 ) content in Sudafed tablets over the 5–350 μM range.     

trans/cis‐Isomerization of Fluorene‐Bridged Azo Chromophore with Significant Two‐Photon Absorbability at Near‐Infrared Wavelength

Azo‐containing materials have been proven to possess second‐order nonlinear optical (NLO) properties, but their third‐order NLO properties, which involves two‐photon absorption (2PA), has rarely been reported. In this study, we demonstrate a significant 2PA behavior of the novel azo chromophore incorporated with bilateral diphenylaminofluorenes (DPAFs) as a π framework. The electron‐donating DPAF moieties cause a redshifted π–π* absorption band centered at 470 nm, thus allowing efficient blue‐light‐induced trans‐to‐cis photoisomerization with a rate constant of 2.04×10^?1 min^?1 at the photostationary state (PSS). The open‐aperture Z‐scan technique that adopted a femtosecond (fs) pulse laser as excitation source shows an appreciably higher 2PA cross‐section for the fluorene‐derived azo chromophore than that for common azobenzene dyes at near‐infrared wavelength (λ_ex=800 nm). Furthermore, the fs 2PA response is quite uniform regardless of the molecular geometry. On the basis of the computational modeling, the intramolecular charge‐transfer (ICT) process from peripheral diphenylamines to the central azo group through a fluorene π bridge is crucial to this remarkable 2PA behavior.     

Multicomponent Supramolecular Systems: Self‐Organization in Coordination‐Driven Self‐Assembly

The self‐organization of multicomponent supramolecular systems involving a variety of two‐dimensional (2 D) polygons and three‐dimensional (3 D) cages is presented. Nine self‐organizing systems, SS₁ – SS₉ , have been studied. Each involves the simultaneous mixing of organoplatinum acceptors and pyridyl donors of varying geometry and their selective self‐assembly into three to four specific 2 D (rectangular, triangular, and rhomboid) and/or 3 D (triangular prism and distorted and nondistorted trigonal bipyramidal) supramolecules. The formation of these discrete structures is characterized using NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS). In all cases, the self‐organization process is directed by: 1) the geometric information encoded within the molecular subunits and 2) a thermodynamically driven dynamic self‐correction process. The result is the selective self‐assembly of multiple discrete products from a randomly formed complex. The influence of key experimental variables ‐ temperature and solvent ‐ on the self‐correction process and the fidelity of the resulting self‐organization systems is also described.     

Barrierless Single‐Electron‐Induced cis–trans Isomerization

Lowering the activation energy of a chemical reaction is an essential part in controlling chemical reactions. By attaching a single electron, a barrierless path for the cis–trans isomerization of maleonitrile on the anionic surface is formed. The anionic activation can be applied in both reaction directions, yielding the desired isomer. We identify the microscopic mechanism that leads to the formation of the barrierless route for the electron‐induced isomerization. The generalization to other chemical reactions is discussed.     

A Visible‐Light‐Triggered Conformational Diastereomer Photoswitch in a Bridged Azobenzene

Ketal‐substituted bridged azobenzenes have been synthesized; these display a symmetrical boat conformation with the ketal in pseudo‐equatorial positions. These bridged Z‐azobenzenes (Z₁) readily photoisomerize to the E‐isomer as well as another Z‐conformer (Z₂) with ketal function on the pseudo‐axial position upon irradiation at 406 nm. The two diastereomeric conformers display distinct physicochemical characteristics. Spectroscopic and NMR investigations supported that interconversion of two conformers occurs via the E‐isomer, with good photochemical quantum yield (Φ =0.45±0.03, Φ =0.33±0.05, Φ =0.37±0.06 and Φ =0.36±0.04). The system shows high photostability and no thermal equilibrium between the two stable Z₁ and Z₂ conformers.     

Spectral Tuning of Azobenzene Photoswitches for Biological Applications

Longer switching wavelengths and good photochemical yields and stabilities of the cis isomers in reducing aqueous environments are achieved by introducing 2,2′‐aminoalkyl substituents into 4,4′‐diamido‐substituted azobenzenes. The products are thus suitable for photocontrol of biomolecular structures in intracellular environments, such as switching between two peptide configurations (see picture).

     

Nonequilibrium structure of cis‐azo compounds in polymethyl methacrylate after photochemical conversion from the trans form

Study was made of the cis → trans isomerization kinetics of a series of azo compounds in polymethyl methacrylate. It was shown that under ultraviolet irradiation a quantity of cis molecules is formed in the stressed states. The stressed cis molecules' relaxation to equilibrium state takes place at temperatures that are far lower than the glass transition temperature. The influence of the relaxation process on the reverse conversion of cis molecules to the trans molecules was investigated along with the influence of temperature. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1753–1761, 1999     

Photoregulation of the Formation and Dissociation of a DNA Duplex by Using the cis–trans Isomerization of Azobenzene

The duplex-forming activity of an oligonucleotide has been photoregulated by making use of the isomerization of an azobenzene moiety in the side chain. When the azobenzene moiety is isomerized from the trans form to the cis form upon photoirradiation, the melting temperature of the duplex between the oligonucleotide and its complementary counterpart is significantly lowered, and the duplex is largely dissociated into two single-stranded oligonucleotides (shown schematically).     

Coordination‐Driven Self‐Assembly of a Molecular Knot Comprising Sixteen Crossings

Molecular knots have become highly attractive to chemists because of their prospective properties in mimicking biomolecules and machines. Only a few examples of molecular knots from the billions tabulated by mathematicians have been realized and molecular knots with more than eight crossings have not been reported to date. We report here the coordination‐driven [8+8] self‐assembly of a higher‐generation molecular knot comprising as many as sixteen crossings. Its solid‐state X‐ray crystal structure and multinuclear 2D NMR findings confirmed its architecture and topology. The formation of this molecular knot appears to depend on the functionalities and geometries of donor and acceptor in terms of generating appropriate angles and strong π‐π interactions supported by hydrophobic effects. This study shows coordination‐driven self‐assembly offers a powerful potential means of synthesizing more and more complicated molecular knots and of understanding differences between the properties of knotted and unknotted structures.     

One‐Pot Multimolecular Macrocyclization for the Expedient Synthesis of Macrocyclic Aromatic Pentamers by a Chain Growth Mechanism

POCl₃‐mediated one‐pot macrocyclization allows the highly selective formation of five‐residue macrocycles that are rigidified by internally placed intramolecular hydrogen bonds. Mechanistic investigation by using tailored competition experiments and kinetic simulation provides a comprehensive model, supporting a chain‐growth mechanism underlying the one‐pot formation of aromatic pentamers, whereby the successive addition of a bifunctional monomer unit onto either another monomer or the growing oligomeric backbone is faster than other types of bimolecular condensations involving oligomers longer than monomers. DFT calculations at the B3LYP/6‐31G* level reveal the five‐residue pentamer to be the most stable with respect to alternative four‐, six‐, and seven‐residue macrocycles. These novel mechanistic insights may become useful in analyzing other macrocyclization, oligomerization, and ploymerization reactions.     

The First Example of Main‐Chain Cyclic Azobenzene Polymers

A novel main‐chain azobenzene cyclic polymer, cyclic‐PEHPA, has been successfully synthesized by ‘click’ cyclization of the α‐alkyne‐ω‐azido hetero‐difunctional linear precursors (linear‐PEHPA), which is synthesized by a step‐growth polymerization of the 3′‐ethynylphenyl[4‐hexyl‐(2‐azido‐2‐methyl‐ propionate) phenyl] azobenzene (EHPA). Gel permeation chromatography, and ¹H NMR and FT‐IR spectra confirmed the complete transformation of linear‐PEHPA into cyclic‐PEHPA. With the same molecular weights, the cyclic‐PEHPAs are found to have higher glass transition temperatures than the linear‐PEHPAs, but almost the same decomposition temperatures. In addition, the obtained cyclic azobenzene polymer with lower molar mass shows a slightly better trans–cis–trans photoisomerization ability than the corresponding linear‐PEHPA.

     

Double Strain‐Promoted Macrocyclization for the Rapid Selection of Cell‐Active Stapled Peptides

Peptide stapling is a method for designing macrocyclic alpha‐helical inhibitors of protein–protein interactions. However, obtaining a cell‐active inhibitor can require significant optimization. We report a novel stapling technique based on a double strain‐promoted azide–alkyne reaction, and exploit its biocompatibility to accelerate the discovery of cell‐active stapled peptides. As a proof of concept, MDM2‐binding peptides were stapled in parallel, directly in cell culture medium in 96‐well plates, and simultaneously evaluated in a p53 reporter assay. This in situ stapling/screening process gave an optimal candidate that showed improved proteolytic stability and nanomolar binding to MDM2 in subsequent biophysical assays. α‐Helicity was confirmed by a crystal structure of the MDM2‐peptide complex. This work introduces in situ stapling as a versatile biocompatible technique with many other potential high‐throughput biological applications.     

Azo Monomers Exhibiting Low Layer Shrinkage at the SmA–SmC Transition and trans–cis Light‐Induced Isomerization

Methacrylic monomers containing a (phenylene)azobenzene unit substituted with a lateral cyano group and alkyl chains of different length are synthesized and characterized by NMR techniques. Their liquid‐crystalline properties are studied by differential scanning calorimetry, polarizing optical microscopy, and X‐ray diffraction. All monomers exhibit a mesomorphic behavior that extends over wide temperature ranges with nematic and orthogonal or tilted smectic‐type mesophases, depending on the length of the terminal chain. The smectic structures are determined to be single‐layered with a low layer shrinkage (<5 %) at the SmA–SmC transition. This atypical behavior is attributed to the combination of a high smectic order promoted by both π–π and bond dipole–bond dipole interactions between cyano‐substituted central cores, and a low correlation between neighboring layers arising from dispersive forces between the end groups (methacrylic group and alkyl chain) of the monomer. On the other hand, the trans–cis isomerization of monomers is induced in solution by irradiating with a UV lamp. High cis‐isomer contents (≥96 %) are obtained at the photostationary state, which is reached in a relatively short time (40 s).     

Coordination‐Driven Switching of a Preorganized and Cooperative Calix[4]pyrrole Receptor

The study of preorganization in receptors, particularly in cooperative receptors, and their reversible control by external stimuli is important for elucidating design strategies that can lead to increased sensitivity and external control of molecular recognition. In this work we present the design, synthesis, and operation of an asymmetric tetrathiafulvalene (TTF)–calix[4]pyrrole receptor appended with a pyridine moiety. ¹H NMR spectroscopy was employed to demonstrate that intramolecular complexation between the receptor and the pyridine moiety leads to a preorganized receptor. Absorption and ¹H NMR spectroscopy along with a computational investigation were used to demonstrate the ability of the receptor to complex the substrate 1,3,5‐trinitrobenzene (TNB) and that the receptor can be reversibly modulated between negative and positive cooperativity by employing external stimuli in the form of Zn^II. Fitting procedures incorporating multiple datasets and fitting to multiple equilibria simultaneously have been employed to quantitatively determine the preorganization effects.