Liquid‐Crystalline Mesogens Based on Cyclo[6]aramides: Distinctive Phase Transitions in Response to Macrocyclic Host–Guest Interactions

Producing macrocyclic mesogens that are responsive to guest encapsulation presents a significant challenge. Cyclo[6]aramides, a type of macrocycle with a hydrogen‐bond‐constrained backbone, exhibit thermotropic lamellar, discotic nematic, hexagonal, and rectangular columnar mesophases over a considerably wide temperature range, including at room temperature. Additionally, cyclo[6]aramides show unusual mesophase transitions from lamellar to hexagonal columnar phase mediated by macrocyclic host–guest (H–G) interactions between the macrocycles and alkylammonium salts. The phase transition, triggered by an organic guest engaging in H–G interactions with a macrocyclic cavity, provides a novel strategy for manipulating the properties of liquid‐crystalline materials. The crystal structure of a homologous cyclo[6]aramide reveals a disk‐shaped, near‐planar molecular backbone that facilitates intermolecular π–π stacking and leads to columnar assembly.     

Chloride‐Anion‐Templated Synthesis of a Strapped‐Porphyrin‐Containing Catenane Host System

The synthesis, structure and anion‐recognition properties of a new strapped‐porphyrin‐containing [2]catenane anion host system are described. The assembly of the catenane is directed by discrete chloride anion templation acting in synergy with secondary aromatic donor–acceptor and coordinative pyridine–zinc interactions. The [2]catenane incorporates a three‐dimensional, hydrogen‐bond‐donating anion‐binding pocket; solid‐state structural analysis of the catenane?chloride complex reveals that the chloride anion is encapsulated within the catenane’s interlocked binding cavity through six convergent CH????Cl and NH???Cl hydrogen‐bonding interactions and solution‐phase ¹H NMR titration experiments demonstrate that this complementary hydrogen‐bonding arrangement facilitates the selective recognition of chloride over larger halide anions in DMSO solution.     

Calix[4]arene‐Based Rotaxane Host Systems for Anion Recognition

The synthesis, structure and anion binding properties of the first calix[4]arene‐based [2]rotaxane anion host systems are described. Rotaxanes 9? Cl and 12? Cl, consisting of a calix[4]arene functionalised macrocycle wheel and different pyridinium axle components, are prepared via adaption of an anion templated synthetic strategy to investigate the effect of preorganisation of the interlocked host’s binding cavity on anion binding. Rotaxane 12? Cl contains a conformationally flexible pyridinium axle, whereas rotaxane 9? Cl incorporates a more preorganised pyridinium axle component. The X‐ray crystal structure of 9? Cl and solution phase ¹H NMR spectroscopy demonstrate the successful interlocking of the calix[4]arene macrocycle and pyridinium axle components in the rotaxane structures. Following removal of the chloride anion template, anion binding studies on the resulting rotaxanes 9? PF₆ and 12? PF₆ reveal the importance of preorganisation of the host binding cavity on anion binding. The more preorganised rotaxane 9? PF₆ is the superior anion host system. The interlocked host cavity is selective for chloride in 1:1 CDCl₃/CD₃OD and remains selective for chloride and bromide in 10 % aqueous media over the more basic oxoanions. Rotaxane 12? PF₆ with a relatively conformationally flexible binding cavity is a less effective and discriminating anion host system although the rotaxane still binds halide anions in preference to oxoanions.     

Integrative Self‐Sorting: One‐Pot Synthesis of a Hetero[4]rotaxane from a Daisy‐Chain‐Containing Hetero[4]pseudorotaxane

The structural complexity of mechanically interlocked molecules are very attractive to chemists owing to the challenges they present. In this article, novel mechanically interlocked molecules with a daisy‐chain‐containing hetero[4]rotaxane motif were efficiently synthesized. In addition, a novel integrative self‐sorting strategy is demonstrated, involving an ABB‐type (A for host, dibenzo‐24‐crown‐8 (DB24C8), and B for guest, ammonium salt sites) monomer and a macrocycle host, benzo‐21‐crown‐7 (B21C7), in which the assembled species in hydrogen‐bonding‐supported solvent only includes a novel daisy‐chain‐containing hetero[4]pseudorotaxane. The found self‐sorting process involves the integrative recognition between B21C7 macrocycles and carefully designed components simultaneously containing two types of secondary ammonium ions and a host molecule, DB24C8 crown ether. The self‐sorting strategy is integrative to undertake self‐recognition behavior to form one single species of pseudorotaxane compared with the previous report. This self‐sorting system can be used for the efficient one‐pot synthesis of a daisy‐chain‐containing hetero[4]rotaxane in a good yield. The structure of hetero[4]rotaxane was confirmed by ¹H NMR spectroscopy and high‐resolution electrospray ionization (HR‐ESI) mass spectrometry.     

Amino Acid Chirality and Ferrocene Conformation Guided Self‐Assembly and Gelation of Ferrocene–Peptide Conjugates

The self‐assembly and gelation behavior of a series of mono‐ and disubstituted ferrocene (Fc)–peptide conjugates as a function of ferrocene conformation and amino acid chirality are described. The results reveal that ferrocene–peptide conjugates self‐assemble into organogels by controlling the conformation of the central ferrocene core, through inter‐ versus intramolecular hydrogen bonding in the attached peptide chain(s). The chirality controlled assembling studies showed that two monosubstituted Fc conjugates FcCO–L FL FL A‐OMe and FcCO–L FL FD A‐OMe form gels with nanofibrillar network structures, whereas the other two diastereomers FcCO–D FL FL A‐OMe and FcCO–L FD FL A‐OMe exclusively produced straight nanorods and non‐interconnected small fibers, respectively. This suggests the potential tuning of gelation behavior and nanoscale morphology by altering the chirality of constituted amino acids. The current study confirms the profound effect of diastereomerism and no influence of enantiomers on gelation. Correspondingly, the diastereomeric and enantiomeric Fc[CO‐FFA‐OMe]₂ were constructed for the study of chirality‐organized structures.     

Metal‐Free Decarboxylative Cyclization/Ring Expansion: Construction of Five‐, Six‐, and Seven‐Membered Heterocycles from 2‐Alkynyl Benzaldehydes and Cyclic Amino Acids

A one pot synthesis of 1H‐benzo[g]indoles, tetrahydrobenzo[h]quinolines, and naphtho[1,2‐b]azepines from 2‐alkynyl benzaldehydes and cyclic amino acids is reported. The salient feature of the strategy involves formation of three new bonds (one C? N and two C? C bonds) by a metal‐free decarboxylation/cyclization/one‐carbon ring expansion sequence in one pot.     

A Dual‐Response [2]Rotaxane Based on a 1,2,3‐Triazole Ring as a Novel Recognition Station

Two novel multilevel switchable [2]rotaxanes containing an ammonium and a triazole station have been constructed by a Cu^I‐catalyzed azide–alkyne cycloaddition reaction. The macrocycle of [2]rotaxane containing a C6‐chain bridge between the two hydrogen bonding stations exhibits high selectivity for the ammonium cation in the protonated form. Interestingly, the macrocycle is able to interact with the two recognition stations when the bridge between them is shortened. Upon deprotonation of both [2]rotaxanes, the macrocycle moves towards the triazole recognition site due to the hydrogen‐bond interaction between the triazole nitrogen atoms and the amide groups in the macrocycle. Upon addition of chloride anion, the conformation of [2]rotaxane is changed because of the cooperative recognition of the chloride anion by a favorable hydrogen‐bond donor from both the macrocycle isophthalamide and thread triazole CH proton.     

Synthesis and characterization of N‐benzoylated wholly aromatic polyamides from 4,4′‐oxydianilinobis(benzimidoyl) chloride and aromatic dicarboxylic acids

A novel type of polyamides, N‐benzoylated wholly aromatic polyamides, were synthesized by low‐temperature solution polycondensation of a new aromatic bis(imidoyl) chloride, 4,4′‐oxydianilinobis(benzimidoyl) chloride, with aromatic dicarboxylic acids, 4,4′‐oxydibenzoic acid and isophthalic acid. Compared with the conventional all aromatic polyamides and also N‐phenylated wholly aromatic polyamides, these N‐benzoylated aramides exhibit better solubility in organic solvents, lower glass transition temperatures and thermal stability.     

A Chiral Halogen‐Bonding [3]Rotaxane for the Recognition and Sensing of Biologically Relevant Dicarboxylate Anions

The unprecedented application of a chiral halogen‐bonding [3]rotaxane host system for the discrimination of stereo‐ and E/Z geometric isomers of a dicarboxylate anion guest is described. Synthesised by a chloride anion templation strategy, the [3]rotaxane host recognises dicarboxylates through the formation of 1:1 stoichiometric sandwich complexes. This process was analysed by molecular dynamics simulations, which revealed the critical synergy of halogen and hydrogen bonding interactions in anion discrimination. In addition, the centrally located chiral (S)‐BINOL motif of the [3]rotaxane axle component facilitates the complexed dicarboxylate species to be sensed via a fluorescence response.     

Spiro[pyrido[3,2,1‐ij]pyrimido[4,5‐b]quinoline‐7,5′‐pyrrolo[2,3‐d]pyrimidines] and Spiro[pyrimido[4,5‐b]quinoline‐5,1′‐pyrrolo[3,2,1‐ij]quinolines] Derived from 5,6‐Dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione

Reaction of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione ( 1 ) with two equivalents of some 6‐aminouracils (or 6‐amino‐2‐thiouracil) generates spirocyclic tetrahydrobenzo[if]quinolizines ( 7 ). The one‐pot, three‐component reaction of amido ketone ( 1 ) with 6‐aminouracil (or 6‐amino‐2‐thiouracil) and a cyclic six‐membered 1,3‐diketone produces spirocyclic tetrahydropyrrolo[3,2,1‐ij]quinolinones ( 15 ).     

High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation

Supramolecular interactions between the host cucurbit[8]uril (CB[8]) and amino acids have been widely interrogated, but recognition of specific motifs within a protein domain have never been reported. A phage display approach was herein used to select motifs with the highest binding affinity for the heteroternary complex with methyl viologen and CB[8] (MV?CB[8]) within a vast pool of cyclic peptide sequences. From the selected motifs, an epitope consisting of three amino acid was extrapolated and incorporated into a solvent‐exposed loop of a protein domain; the protein exhibited micromolar binding affinity for the MV?CB[8] complex, matching that of the cyclic peptide. By achieving selective CB[8]‐mediated conjugation of a small molecule to a recombinant protein scaffold we pave the way to biomedical applications of this simple ternary system.     

Synthesis and reactivity of cyanomethyl 2‐amino‐4‐methylthiazolyl ketone. A facile synthesis of novel pyrazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazino[4,3‐a]benzimidazole,pyridazine‐6‐imine and 6‐oxopyridazinone derivatives

The novel and versatile cyanomethyl 2‐amino‐4‐methylthiazolyl ketone (5) was prepared by treatment of bromomethyl 2‐amino‐4‐methyl thiazolyl ketone (4) with potassium cyanide. Reaction of 5 with heterocyclic diazonium salts 6a,b and 10 afforded the corresponding hydrazones 7a,b and 11, respectively. Refluxing of the hydrazones in pyridine afforded the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine, and 1,2,4‐triazolo[4,3‐a]benzimidazole derivatives 8a,b and 12, respectively, via intramolecular cyclization. Compound 5 coupled also with benzenediazonium chloride to afford the corresponding hydrazone 14, which is an excellent precursor for the synthesis of pyridazine‐6‐imine 17a and pyridazinone 17b. The pyridazine derivatives 17a,b were also prepared by an independent route, that is, the condensation with malononitriles and coupling with benzenediazonium chloride, followed by intramolecular cyclization. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 385–390, 1999     

Five‐State Molecular Shuttling of a Pair of [2]Rotaxanes: Distinct Outputs in Response to Acid and Base Stimuli

In this study we synthesized two acid‐/base‐controllable [2]rotaxanes featuring aminodiazobenzene and aminocoumarin units, respectively, as chromophores and dibenzo[24]crown‐8 and dibenzo[25]crown‐8 units, respectively, as their macrocyclic components. Each [2]rotaxane contained N‐alkylarylamine (ammonium) and N,N‐dialkylamine (ammonium) centers as binding sites for their crown ether components. The absorption patterns of the chromophores were dependent on the position of the encircling macrocyclic component and the degree of protonation, with three distinct states (under acidic, neutral, and basic conditions) evident for each [2]rotaxane. The mixed [2]rotaxane system displayed stepwise and independent molecular shuttling behavior based on the degree of protonation of the amino groups in response to both the amount and strength of added acids or bases; as such, the system provided five different absorption signals as outputs that could be read using UV/Vis spectroscopy.     

Reaction of 2‐acyl‐6‐methylbenzo[b]furan‐3‐acetic acids derivatives with hydrazine

Reaction of 2‐acyl‐6‐methylbenzo[b]furan‐3‐acetic acids and their derivatives such as amides and esters with hydrazine does not give expected 1‐alkyl‐5H‐benzofuro[2,3‐e]diazepin‐4‐ones ones but results in 2‐amino‐7‐methyl‐2H‐benzo[4,5]furo[2,3‐c]pyridin‐3‐ones or (3‐R‐6‐methylbenzo[b]furan‐2‐yl)alkyl ketone azines.     

New Convenient Five‐Component One‐Pot Synthesis of 3‐Alkyl‐6‐amino‐1,4‐dihydro‐4‐{[(1,2,3‐triazol‐4‐yl)methoxy]phenyl}pyrano[2,3‐c]pyrazole‐5‐carbonitrile Derivatives

3‐Alkyl‐6‐amino‐1,4‐dihydro‐4‐{[(1,2,3‐triazol‐4‐yl)methoxy]phenyl}pyrano[2,3‐c]pyrazole‐5‐carbonitrile derivatives were synthesized through a one‐pot five‐component condensation reaction.     

Mono‐6A‐(4‐methoxybutylamino)‐6A‐β‐cyclodextrin as a chiral selector for enantiomeric separation

A new member of the family of methoxylalkylamino monosubstituted β‐cyclodextrins, mono‐6^A‐(4‐methoxybutylamino)‐6^A‐β‐cyclodextrin, has been developed as a chiral selector for enantioseparation in capillary electrophoresis. This amino cyclodextrin exhibited good enantioselectivities for 16 model acidic racemates including three dansyl amino acids at an optimum pH of 6.0. Excellent chiral resolutions over six were obtained for α‐hydroxy acids and 2‐phenoxypropionic acids with 3.0 mM chiral selector. The good chiral recognition for α‐hydroxyl acids was attributed to inclusion complexation, electrostatic interactions, and hydrogen bonding. The hydrogen‐bonding‐enhanced chiral recognition was revealed by NMR spectroscopy. The chiral separation of acidic racemates was further improved with the addition of methanol (≤10 vol%) as an organic additive.     

A facile one step synthesis of 1,6 ‐dihydro‐7H‐pyrazolo[4,3‐d]‐pyrimidin‐7‐ones

A general synthetic approach to pyrazolo[4,3‐d]pyrimidines is reported. Aldehydes, arylideneanilines, carboxylic acids and orthoesters are used as one‐carbon units for bridging the two amino functions of 4‐amino‐1‐alkyl‐3‐propylpyrazole‐5‐carboxamides.     

Four‐State Molecular Shuttling of [2]Rotaxanes in Response to Acid/Base and Alkali‐Metal Cation Stimuli

In this study, we synthesized [2]rotaxanes possessing three recognition sites—a dialkylammonium, an alkylarylamine, and a tetra(ethylene glycol) stations—in their dumbbell‐like axle component and dibenzo[24]crown‐8 (DB24C8) as their macrocyclic component. These [2]rotaxanes behaved as four‐state molecular shuttles: i) under acidic conditions, the DB24C8 unit encircled both the dialkylammonium and alkylarylammonium stations; ii) under neutral conditions, the dialkylammonium unit was the predominant station for the DB24C8 component; iii) under basic conditions, when both ammonium centers were deprotonated, the alkylarylamine unit became a suitable station for the DB24C8 component; and iv) under basic conditions in the presence of an alkali‐metal cation, the tetra(ethylene glycol) unit recognized the DB24C8 component through cooperative binding of the alkali‐metal ion. In addition, we observed that the [2]rotaxanes exhibited selective recognition for metal cations. These shuttling motions of the macrocyclic component proceeded reversibly.     

A Synthetic Adenylation‐Domain‐Based tRNA‐Aminoacylation Catalyst

The incorporation of non‐proteinogenic amino acids represents a major challenge for the creation of functionalized proteins. The ribosomal pathway is limited to the 20–22 proteinogenic amino acids while nonribosomal peptide synthetases (NRPSs) are able to select from hundreds of different monomers. Introduced herein is a fusion‐protein‐based design for synthetic tRNA‐aminoacylation catalysts based on combining NRPS adenylation domains and a small eukaryotic tRNA‐binding domain (Arc1p‐C). Using rational design, guided by structural insights and molecular modeling, the adenylation domain PheA was fused with Arc1p‐C using flexible linkers and achieved tRNA‐aminoacylation with both proteinogenic and non‐proteinogenic amino acids. The resulting aminoacyl‐tRNAs were functionally validated and the catalysts showed broad substrate specificity towards the acceptor tRNA. Our strategy shows how functional tRNA‐aminoacylation catalysts can be created for bridging the ribosomal and nonribosomal worlds. This opens up new avenues for the aminoacylation of tRNAs with functional non‐proteinogenic amino acids.     

Programming A Molecular Relay for Ultrasensitive Biodetection through 129Xe NMR

A supramolecular strategy for detecting specific proteins in complex media by using hyperpolarized ¹²⁹Xe NMR is reported. A cucurbit[6]uril (CB[6])‐based molecular relay was programmed for three sequential equilibrium conditions by designing a two‐faced guest (TFG) that initially binds CB[6] and blocks the CB[6]–Xe interaction. The protein analyte recruits the TFG and frees CB[6] for Xe binding. TFGs containing CB[6]‐ and carbonic anhydrase II (CAII)‐binding domains were synthesized in one or two steps. X‐ray crystallography confirmed TFG binding to Zn²⁺ in the deep CAII active‐site cleft, which precludes simultaneous CB[6] binding. The molecular relay was reprogrammed to detect avidin by using a different TFG. Finally, Xe binding by CB[6] was detected in buffer and in E. coli cultures expressing CAII through ultrasensitive ¹²⁹Xe NMR spectroscopy.